Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Myeloid Sarcoma after Allogenic Stem Cell Transplantation for Acute Myeloid Leukemia: Successful Consolidation Treatment Approaches in Two Patients

Myeloid Sarcoma after Allogenic Stem Cell Transplantation for Acute Myeloid Leukemia: Successful... Hindawi Case Reports in Oncological Medicine Volume 2018, Article ID 7697283, 5 pages https://doi.org/10.1155/2018/7697283 Case Report Myeloid Sarcoma after Allogenic Stem Cell Transplantation for Acute Myeloid Leukemia: Successful Consolidation Treatment Approaches in Two Patients 1 2 1 1,3 Silje Johansen, Hilde Kollsete Gjelberg, Aymen Bushra Ahmed, Øystein Bruserud , 1,3 and Ha˚kon Reikvam Section of Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway Department of Clinical Science, University of Bergen, 5021 Bergen, Norway Correspondence should be addressed to Ha˚kon Reikvam; hakon.reikvam@med.uib.no Received 7 October 2017; Accepted 1 February 2018; Published 28 February 2018 Academic Editor: Jose I. Mayordomo Copyright © 2018 Silje Johansen et al. ,is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Myeloid sarcoma is an extramedullary (EM) manifestation (i.e., manifestation outside the bone marrow) of acute myeloid leukemia (AML); it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT). An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. ,e development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD), and treatment with donor lymphocytes infusion (DLI). It is believed that posttransplant myeloid sarcomas develop because the EM sites evade immune surveillance. We present two patients with EM myeloid sarcoma in the breast and epipharynx, respectively, as the only manifestation of leukemia relapse. Both patients were treated with a combination of local and systemic therapy, with successfully longtime disease-free survival. Based on these two case reports, we give an updated review of the literature and discuss the pathogenesis, diagnosis, and treatment of EM sarcoma as the only manifestation of AML relapse after allo-SCT. ,ere are no standard guidelines for the treatment of myeloid sarcomas in allotransplant recipients. In our opinion, the treatment of these patients needs to be individualized and should include local treatment (i.e., radiotherapy) combined with systemic therapy (i.e., chemotherapy, immunotherapy, DLI, or retransplantation). ,e treatment has to consider both the need for sufficient antileukemic efficiency versus the risk of severe complications due to cumulative toxicity. marrow examination then showed 90% myeloblasts, with 1. Introduction immunophenotype CD45dim/117+/13dim/33+/56−/2−/15−/ Myeloid sarcoma is a rare manifestation of AML and can appear 14−/11b−/99+/HLA-DR−; CD34 positivity was detected for concomitantly with, following or rarely antedating the onset of a subpopulation of 8% of blasts. Karyotyping showed t(7;11) as bone marrow leukemia [1]. MS can be the sole manifest of AML the only cytogenetic abnormality; this translocation between relapse after allo-SCT. We describe two patients presenting with chromosomes 7p15 and 11p15 involved the NUP98 gene on myeloid sarcoma as the only sign of AML relapse after allo-SCT. chromosome 11. Medical termination was performed before she We discuss diagnostic and therapeutic aspects of this assumed received conventional induction therapy with daunorubicin 2 2 rare manifestation of relapse after allo-SCT. 50 mg/m once daily on days 1–3 and cytarabine 200 mg/m as daily continuous infusion on days 1–7, and she reached complete hematological remission after this single induction 2. Patients cycle. ,is treatment was followed by consolidation therapy 2.1. Patient 1. ,e patient was a 40-year-old Asian female with 4 cycles of high-dose cytarabine, each of these cycles diagnosed with AML during pregnancy (Figure 1). ,e bone consisting of cytarabine 3 g/m twice daily on days 1, 3, and 5. 2 Case Reports in Oncological Medicine without any signs of leukemia for 22 months after diagnosis of Induction (7 + 3) Allo-SCT Radiotherapy DLI relapse as MS. Consolidation MAE Induction (7 + 3) DLI II DLI III Induction (7 + 3) 2.2. Patient 2. €is patient was a 34-year-old Caucasian male diagnosed with normal karyotype AML (46, XY) without mutations in the FLT3 or NPM1 genes (Figure 3). With y0 y1 y2 y7 y8 multiparameter šow cytometric analysis, the immunopheno- AML Relapse Myeloid GVHD type was described as CD7+/CD11c+/CD13+/CD14−/CD15−/ AML sarcoma CD33+/CD34+/CD117+/HLA-DR+. CD56 was positive only for 3% of blast cells. €e rst induction cycle included Figure 1: Timeframe regarding diagnosis and treatment of patient 1. cytarabine plus an anthracycline (idarubicin 12 mg/m once €e gure presents the main treatment features and therapeutic daily on days 1–3 and cytarabine 200 mg/m as daily contin- approaches in patient 1. uous infusion on days 1–7). However, he had persistent leu- kemic blasts in the bone marrow 16 days after start of this cycle; additional treatment with cytarabine and idarubicin (idar- Relapsed disease was diagnosed 24 months after the rst ubicin 12 mg/m once daily on days 1 and 2; cytarabine treatment was completed; at the time of relapse, she was 200 mg/m as daily continuous infusion on days 1–5) was pregnant in the 28th week and she was induced for labor in the started the next day. He now reached a complete hematological 29th week. Cytogenetic analysis detected the original t(7;11) remission and received consolidation with another cycle of translocation in 6 out of 14 metaphases, and additional t(12;17) cytarabine plus idarubicin (5 + 2 regimen) and thereafter one with a translocation between chromosome 12p11 and 17q11 cycle of high-dose cytarabine. €e patient proceeded to allo- was also detected together with loss of the derivative chro- SCT with myeloablative conditioning based on busulfan plus mosome 17. €e latter abnormality leads to the loss of genes on cyclophosphamide with an HLA-matched sibling donor. 21 17p including the p53 gene. €e immunophenotypic features months after the transplantation, he presented with increased were similar as at initial diagnosis. New induction treatment liver enzymes and histological changes in his oral cavity was performed by idarubicin 12 mg/m once daily on days 1–3 con rmed by biopsy to be chronic GVHD (cGVHD). €irty- and cytarabine 200 mg/m as daily continuous infusion on nine months after allo-SCT, he presented with symptoms from days 1–7, and again she reached complete hematological re- his left ear, and he was diagnosed with an epipharyngeal tumor; mission after one induction cycle. €en she was given further biopsies from this lesion demonstrated tumor of myeloid origin consolidation therapy with one cycle of amsakrin 150 mg/m (Figure 4). €e tumor cells stained negative for CD56 with once daily on days 1–5, etoposide 110 mg/m once daily on immunohistochemistry. His bone marrow showed normal days 1–5, and cytarabine 200 mg/m as daily continuous in- cellularity with no signs of leukemia. €us, he had MS as the fusion on days 1–5. After this, she proceeded to myeloablative only manifestation of posttransplant AML relapse. He received conditioning (MAC) allo-SCT with a matched sibling donor. induction treatment with amsakrin 150 mg/m once daily on She showed no sign of GVHD at any time after the trans- days 1–5, etoposide 110 mg/m once daily on days 1–5, and plantation, and she achieved full donor chimerism. cytarabine 200 mg/m as daily continuous infusion on days She presented with a tumor in her left breast 62 months 1–5; peripheral blood and bone marrow examination were after the allo-SCT, and biopsy con rmed the diagnosis of consistent with complete hematological remission, and MRI myeloid sarcoma (Figure 2). Immunophenotypic features showed regress of the epipharyngeal tumor. €e consolidation were compatible with AML clone found at diagnosis and rst treatment was radiotherapy with 2 Gy × 20 (totally 40 Gy). relapse, although CD56 was dim positive. Positron emission After this treatment, he developed mucosal skin lesions in tomography (PET) scan showed increased uptake in the mouth consistent with cGVHD; for this reason, he never re- tumor as well as two smaller lesions in the right breast. Bone ceived DLI. MRI taken after completion of radiotherapy marrow examination showed no evidence of AML by mor- showed total regress of the tumor. He is still in complete re- phological and šow cytometric examination. She received mission 72 months after the diagnosis of relapse. induction treatment by idarubicin 12 mg/m once daily on days 1–3 and cytarabine 200 mg/m as daily continuous in- fusion on days 1–7. Control PET examination after one in- 3. Discussion duction cycle showed complete regression of šuorodeoxyglucose (FDG) uptake in the left breast. €e patient denied further MS is a tumor of immature myeloid cells located at an intensive chemotherapy and retransplantation. She therefore extramedullary (EM) site; it can develop in any organ or site in received consolidation treatment by radiation therapy the body but is more common at the immunological sanc- 2 Gy × 15 (total dose 30 Gy) against both breasts. In addition, tuary sites of the testis, ovary, and central nervous system she received three donor lymphocyte infusions (DLIs) in total (CNS) [2, 3]. Results from a multicenter survey implies skin 1.6 ×10 cells/kg; G-CSF-primed cells harvested at the time of and lymph nodes as frequently involved in de novo MS, stem cell harvesting were used for all three DLIs. After the last whereas soft tissues are more often involved in secondary MS DLI, she presented with oral and skin manifestations con- [3]. €e involvement of breast is uncommon [4], although sistent with GVHD and this diagnosis was con rmed with reported with relapsed disease [5]. €us, both our patients biopsy/histology. She has now been in complete remission with posttransplant MS had uncommon localizations. Case Reports in Oncological Medicine 3 (b) (a) (c) Figure 2: Stained biopsy from patient 1. (a) Histologic image (hematoxylin/eosin staining) of the breast biopsy showing a di¨use in ltrate of tumor cells with scant cytoplasm and large nuclei with “open” chromatin pattern and distinct nucleoli, consistent with blasts. €e blasts in ltrate around small residual acini (black arrows) in a lobule (white arrow). (b) €e tumor cells are myeloperoxidase positive by immunohistochemistry. (c) Dim to moderate positivity by immunohistochemical staining for CD56. Size bars: 80 μm. An EM AML relapse will usually progress to involve Induction (7 + 3) Radiotherapy other EM sites as well as the bone marrow within one year Induction II (5 + 2) Induction (MAE) [2]. €e incidence of EM AML relapse after allo-SCTof AML Consolidation (5 + 2) was 0.65% in a large retrospective study from the European Consolidation (cytarabine) Group of Blood and Marrow Transplantation (EBMT) [6]. Allo-SCT However, recent studies indicate that the incidence is higher, y0 y1 y2 y3 and posttransplant EM relapse has been described in 5–12% of allotransplanted AML patients, accounting for 7–46% of AML Chronic GVHD Myeloid all AML relapses [2, 7, 8]. Among longtime survivals, the sarcoma incidence has been reported to be as high as 20% [2, 9], and Figure 3: Timeframe regarding diagnostic and treatment of patient 2. EM relapse has been described until several years after €e gure presents the main treatment features and therapeutic transplantation [2, 5]. €e diagnosis is often delayed and the approaches in patient 2. relapse is usually diagnosed when it becomes symptomatic, because no standardized strategy for the surveillance to detect posttransplant EM relapse exists [7]. Measurable It is believed that the general immune-mediated anti- residual disease (MRD), either by multiparameter šow leukemic reactivity mediated by the general graft versus host cytometry or by genetic molecular markers, is established as reactivity that is associated with the occurrence of GVHD an independent prognostic marker in AML [10]. However, preferentially maintains bone marrow remission but does the methodology of these approaches has currently not been not prevent EM relapse [8]. €e occurrence of acute GVHD qualitatively or quantitatively standardized, making their use (aGVHD) is signi cantly associated with better bone mar- in clinical practice challenging [10], and none of our patients row relapse-free survival; however, the EM relapse rate for was followed by MRD monitoring. Furthermore, if detecting patients with or without a GVHD seems to be similar [7]. €ere are several possible explanations for this phenome- of MRD could proceed, diagnosis of EM AML relapse re- mains elusive, although should be further investigated in non. Firstly, AML cells in peripheral tissues may evade upcoming clinical trials. immune surveillance [2], as the number of e¨ector cells for €e best treatment of isolated EM relapse after allo-SCT immune-mediated antileukemic reactivity is higher in the is unknown [8, 11]. Previous induction and conditioning bone marrow. €e partial loss of several human leukocyte treatment causing cumulative toxicities and high-dose antigen (HLA) class I genes may further decrease the general chemotherapy with suppression of the graft versus leuke- e§ciency of the antileukemic immune reactivity [7]. Sec- mia (GVL) reactivity have to be considered when deciding ondly, the CD56 expression in AML cells mediates cell-cell a therapeutic strategy with su§cient antileukemic e§ciency adhesion and is highly expressed in various tissues; these versus the risk of severe and unacceptable toxicity [8, 11]. €e adhesion molecules seem to be involved in EM homing and prognosis of solitary EM relapse remains poor, although it may then support EM AML cell survival [7]. It has been suggested that the CD56 cell surface expression together with seems slightly better than bone marrow relapse alone or combined bone marrow and EM relapse [7]. the encoded fusion proteins in patients with the chromosomal 4 Case Reports in Oncological Medicine (b) (a) (c) Figure 4: Stained biopsy from patient 2. (a) Subepithelial di¨use in ltrate of blasts in the biopsy specimen from the epipharyngeal lesion (hematoxylin/eosin staining). Black arrow: respiratory epithelium. (b) Virtually all the blasts are myeloperoxidase positive by immu- nohistochemistry. (c) €e tumor cells are negative for CD56. Size bars: 80 μm. prognosis [3], and treatment approaches for EM relapse after abnormalities t(8:21) and inv(16) is associated with EM AML cell in ltration [7], although it is unknown whether these allo-SCT should probably involve combination of local and systemic therapy to prevent systemic relapse [7, 16]. mechanisms are important for posttransplant EM relapse [7]. EM presentation has also been associated with other Treatment options for patients with EM relapse should chromosomal abnormalities like trisomy of chromosomes 4, be considered individually [17]. Since radiological exami- 8, and 11 as well as deletion of chromosomes 5q, 16q, and 20q nation after induction treatment did not reveal disease ac- [12]. Noteworthy, the myoblast for one of our patients was tivity in the breasts for our rst patient, further surgery was only dim positive for CD56 in the biopsy of the relapsed EM therefore not performed. DLI is regarded as an e¨ective AML in the breast, and for the other patient only 3% of the treatment of posttransplant bone marrow relapse, although blast cells at the time of AML diagnosis was CD56 positive. may not be equally e¨ective for EM relapse [2, 18]. However, €irdly, some studies suggest that EM relapse is higher after the combination of DLI with chemotherapy will often make it di§cult to di¨erentiate the e¨ects of the immunotherapy allo-SCT compared to auto-SCT and that the incidence of MS relapse seems to be increased after DLI and in and the chemotherapy [2]. Only one of our patients received DLI, although discontinued after three infusions because of retransplanted patients [7, 13–15]. Other factors associated with increased risk of EM after allotransplantation are re- GVHD. €e curative e¨ect of allo-SCT in AML is considered lapsed or refractory disease at time of transplant, unfavorable to be due to a combined e¨ect of conditioning chemotherapy cytogenetics, EM disease before allo-SCT, retransplantation, and posttransplant immune-mediated antileukemic activity, age below 18 years, and FAB subtypes M4/M5 [7, 12]. Finally, and for this reason it is probably important to maintain this if certain pretransplant conditioning regimens are more ef- immune reactivity in patients with EM relapse [8]. fective with regard to prevention of posttransplant EM relapse A possible treatment for isolated EM relapse is is unknown [7]. None of these risk factors were present in our gemtuzumab/ozogamicin (GO), acting by depleting CD33- patients. Both patients were in complete hematological re- expressing leukemic cells and possible bolstering antileu- kemic immune reactivity [8, 19]. €e risk of severe toxicity mission at the time of transplantation, they received busulfan- based conditioning, and one of them had clinical signs of and especially hepatic injury with veno-occlusive disease GVHD before EM relapse was diagnosed. (VOD) should be taken into account [8]. Another systemic €ere are no established guidelines for the treatment of active agent that does not abrogate the antileukemic immune EM relapse after allo-SCT. €e common practice is a com- reactivity is the hypomethylating agents 5-azacitidine and bination of local and systemic treatment including intensive decitabine, which even might enhance the GVL e¨ect. €ese chemotherapy, local radiotherapy, DLI, and/or retrans- agents induce AML cell di¨erentiation and increase the ex- plantation [2, 9]. Anti-AML therapy seems to be e¨ective in pression of HLA antigens as well as tumor-associated antigens patients presenting with MS alone [1], and systemic che- [7]; this strategy is used for the treatment of posttransplant motherapy is required rather than surgery or radiotherapy bone marrow relapse of both AML and myelodysplastic alone to prevent relapse and disease progression. However, syndromes (MDS) [7, 9]. Case reports suggest that these agents may be e¨ective even for patients with posttransplant many of these previous studies do not di¨erentiate between de novo and secondary MS with regard to treatment and EM and previous treatment failure after DLI, radiotherapy, Case Reports in Oncological Medicine 5 Group for Blood and Marrow Transplantation,” Bone Marrow and intensive chemotherapy [9, 20]. Finally, CD56 expres- Transplantation, vol. 17, no. 5, pp. 801–808, 1996. sion in leukemic cells and antibodies conjugated with a [7] S. Yoshihara, T. Ando, and H. Ogawa, “Extramedullary re- toxin or a radioisotope may represent future strategies for lapse of acute myeloid leukemia after allogeneic hemato- the treatment of these patients [7]. poietic stem cell transplantation: an easily overlooked but significant pattern of relapse,” Biology of Blood and Marrow 4. Conclusion Transplantation, vol. 18, no. 12, pp. 1800–1807, 2012. [8] T. Ando, N. Mitani, K. Matsunaga et al., “Gemtuzumab EM posttransplant AML relapse may be more common ozogamicin therapy for isolated extramedullary AML relapse than previously assumed, and its prognosis remains poor after allogeneic hematopoietic stem-cell transplantation,” even though possibly slightly better than for combined EM Tohoku Journal of Experimental Medicine, vol. 220, no. 2, and bone marrow relapse or bone marrow relapse alone. pp. 121–126, 2010. [9] A. Antar, Z. K. Otrock, M. Kharfan-Dabaja et al., “Azacitidine No guidelines for standard treatment of these patients are in the treatment of extramedullary relapse of AML after al- available, but a common practice is systemic chemotherapy logeneic hematopoietic cell transplantation,” Bone Marrow or immunotherapy (i.e., DLI or retransplantation) com- Transplantation, vol. 48, no. 7, pp. 994-995, 2013. bined with local radiotherapy. Cumulative toxicities due to [10] G. J. Schuurhuis, M. Heuser, S. Freeman et al., “Minimal/ previous chemotherapy and the risk of suppressing clini- measurable residual disease in AML: consensus document cally relevant antileukemic immune reactivity have to be from ELN MRD Working Party,” Blood, 2018, In press. considered when the treatment of such patients is decided. [11] Y. Koc, K. B. Miller, D. P. Schenkein, P. Daoust, K. Sprague, Our two patients received intensive chemotherapy in- and E. Berkman, “Extramedullary tumors of myeloid blasts in duction followed by consolidating radiotherapy, and only adults as a pattern of relapse following allogeneic bone one of them received DLI; both patients are still alive marrow transplantation,” Cancer, vol. 85, no. 3, pp. 608–615, without relapse. Future studies should focus on the de- 1999. [12] M. Solh, S. Solomon, L. Morris, K. Holland, and A. Bashey, velopment of diagnostic strategies for earlier detection of “Extramedullary acute myelogenous leukemia,” Blood Re- EM relapse and the identification of molecular mechanisms views, vol. 30, no. 5, pp. 333–339, 2016. (i.e., possible therapeutic targets) behind EM homing of [13] S. J. Choi, J. H. Lee, J. H. Lee et al., “Treatment of relapsed leukemic cells. acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF- Conflicts of Interest primed donor leukocyte infusion: a high incidence of iso- lated extramedullary relapse,” Leukemia, vol. 18, no. 11, ,e authors declare that they have no conflicts of interest. pp. 1789–1797, 2004. [14] S. Singhal, R. Powles, S. Kulkarni, J. Treleaven, R. Saso, and J. Mehta, “Long-term follow-up of relapsed acute leukemia Acknowledgments treated with immunotherapy after allogeneic transplantation: the inseparability of graft-versus-host disease and graft-versus- ,e study was supported by Øyvinn Mølbach-Pedersen’s leukemia, and the problem of extramedullary relapse,” Leu- Foundation, Helse Vest, and the Norwegian Cancer Society. kemia & Lymphoma, vol. 32, no. 5-6, pp. 505–512, 1999. [15] A. Takami, H. Okumura, H. Yamazaki et al., “Prospective trial References of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for [1] A. M. Tsimberidou, H. M. Kantarjian, S. Wen et al., “Myeloid relapsed leukemia after allogeneic stem cell transplantation,” sarcoma is associated with superior event-free survival and International Journal of Hematology, vol. 82, no. 5, pp. 449–455, overall survival compared with acute myeloid leukemia,” Cancer, vol. 113, no. 6, pp. 1370–1378, 2008. [16] M. Solh, T. E. DeFor, D. J. Weisdorf, and D. S. Kaufman, [2] W. B. Clark, S. A. Strickland, A. John Barrett, and B. N. Savani, “Extramedullary relapse of acute myelogenous leukemia after “Extramedullary relapses after allogeneic stem cell trans- allogeneic hematopoietic stem cell transplantation: better plantation for acute myeloid leukemia and myelodysplastic prognosis than systemic relapse,” Biology of Blood and syndrome,” Haematologica, vol. 95, no. 6, pp. 860–863, 2010. Marrow Transplantation, vol. 18, no. 1, pp. 106–112, 2012. [3] D. Lazzarotto, A. Candoni, C. Fil`ı et al., “Clinical outcome of [17] R. L. Bakst, M. S. Tallman, D. Douer, and J. Yahalom, “How I myeloid sarcoma in adult patients and effect of allogeneic treat extramedullary acute myeloid leukemia,” Blood, vol. 118, stem cell transplantation. Results from a multicenter survey,” no. 14, pp. 3785–3793, 2011. Leukemia Research, vol. 53, pp. 74–81, 2017. [18] C. Berthou, M. C. Leglise, A. Herry et al., “Extramedullary [4] X. E. Huang, Y. J. Li, and X. D. Zhou, “Granulocytic sarcoma relapse after favorable molecular response to donor leukocyte of the breast: a case report,” Oncology Letters, vol. 10, no. 4, infusions for recurring acute leukemia,” Leukemia, vol. 12, pp. 2447–2449, 2015. no. 11, pp. 1676–1681, 1998. [5] Y. Lou, W. Qian, H. Meng, Y. Tong, and J. Jin, “Frequent [19] T. Owonikoko, M. Agha, R. Balassanian, R. Smith, and extramedullary recurrence of isolated myeloid sarcoma in the A. Raptis, “Gemtuzumab therapy for isolated extramedullary long-term follow-up,” Annals of Hematology, vol. 91, no. 8, AML relapse following allogeneic stem-cell transplant,” Nature pp. 1317–1319, 2012. Clinical Practice Oncology, vol. 4, no. 8, pp. 491–495, 2007. [6] A. N. Bekassy, J. Hermans, N. C. Gorin, and A. Gratwohl, [20] E. Jabbour, S. Giralt, H. Kantarjian et al., “Low-dose azaci- “Granulocytic sarcoma after allogeneic bone marrow trans- tidine after allogeneic stem cell transplantation for acute plantation: a retrospective European multicenter survey. leukemia,” Cancer, vol. 115, no. 9, pp. 1899–1905, 2009. Acute and Chronic Leukemia Working Parties of the European MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Myeloid Sarcoma after Allogenic Stem Cell Transplantation for Acute Myeloid Leukemia: Successful Consolidation Treatment Approaches in Two Patients

Download PDF
6 pages

Loading next page...
 
/lp/hindawi-publishing-corporation/myeloid-sarcoma-after-allogenic-stem-cell-transplantation-for-acute-u81r8QCj48

References (24)

Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2018 Silje Johansen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
2090-6706
eISSN
2090-6714
DOI
10.1155/2018/7697283
Publisher site
See Article on Publisher Site

Abstract

Hindawi Case Reports in Oncological Medicine Volume 2018, Article ID 7697283, 5 pages https://doi.org/10.1155/2018/7697283 Case Report Myeloid Sarcoma after Allogenic Stem Cell Transplantation for Acute Myeloid Leukemia: Successful Consolidation Treatment Approaches in Two Patients 1 2 1 1,3 Silje Johansen, Hilde Kollsete Gjelberg, Aymen Bushra Ahmed, Øystein Bruserud , 1,3 and Ha˚kon Reikvam Section of Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway Department of Clinical Science, University of Bergen, 5021 Bergen, Norway Correspondence should be addressed to Ha˚kon Reikvam; hakon.reikvam@med.uib.no Received 7 October 2017; Accepted 1 February 2018; Published 28 February 2018 Academic Editor: Jose I. Mayordomo Copyright © 2018 Silje Johansen et al. ,is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Myeloid sarcoma is an extramedullary (EM) manifestation (i.e., manifestation outside the bone marrow) of acute myeloid leukemia (AML); it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT). An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. ,e development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD), and treatment with donor lymphocytes infusion (DLI). It is believed that posttransplant myeloid sarcomas develop because the EM sites evade immune surveillance. We present two patients with EM myeloid sarcoma in the breast and epipharynx, respectively, as the only manifestation of leukemia relapse. Both patients were treated with a combination of local and systemic therapy, with successfully longtime disease-free survival. Based on these two case reports, we give an updated review of the literature and discuss the pathogenesis, diagnosis, and treatment of EM sarcoma as the only manifestation of AML relapse after allo-SCT. ,ere are no standard guidelines for the treatment of myeloid sarcomas in allotransplant recipients. In our opinion, the treatment of these patients needs to be individualized and should include local treatment (i.e., radiotherapy) combined with systemic therapy (i.e., chemotherapy, immunotherapy, DLI, or retransplantation). ,e treatment has to consider both the need for sufficient antileukemic efficiency versus the risk of severe complications due to cumulative toxicity. marrow examination then showed 90% myeloblasts, with 1. Introduction immunophenotype CD45dim/117+/13dim/33+/56−/2−/15−/ Myeloid sarcoma is a rare manifestation of AML and can appear 14−/11b−/99+/HLA-DR−; CD34 positivity was detected for concomitantly with, following or rarely antedating the onset of a subpopulation of 8% of blasts. Karyotyping showed t(7;11) as bone marrow leukemia [1]. MS can be the sole manifest of AML the only cytogenetic abnormality; this translocation between relapse after allo-SCT. We describe two patients presenting with chromosomes 7p15 and 11p15 involved the NUP98 gene on myeloid sarcoma as the only sign of AML relapse after allo-SCT. chromosome 11. Medical termination was performed before she We discuss diagnostic and therapeutic aspects of this assumed received conventional induction therapy with daunorubicin 2 2 rare manifestation of relapse after allo-SCT. 50 mg/m once daily on days 1–3 and cytarabine 200 mg/m as daily continuous infusion on days 1–7, and she reached complete hematological remission after this single induction 2. Patients cycle. ,is treatment was followed by consolidation therapy 2.1. Patient 1. ,e patient was a 40-year-old Asian female with 4 cycles of high-dose cytarabine, each of these cycles diagnosed with AML during pregnancy (Figure 1). ,e bone consisting of cytarabine 3 g/m twice daily on days 1, 3, and 5. 2 Case Reports in Oncological Medicine without any signs of leukemia for 22 months after diagnosis of Induction (7 + 3) Allo-SCT Radiotherapy DLI relapse as MS. Consolidation MAE Induction (7 + 3) DLI II DLI III Induction (7 + 3) 2.2. Patient 2. €is patient was a 34-year-old Caucasian male diagnosed with normal karyotype AML (46, XY) without mutations in the FLT3 or NPM1 genes (Figure 3). With y0 y1 y2 y7 y8 multiparameter šow cytometric analysis, the immunopheno- AML Relapse Myeloid GVHD type was described as CD7+/CD11c+/CD13+/CD14−/CD15−/ AML sarcoma CD33+/CD34+/CD117+/HLA-DR+. CD56 was positive only for 3% of blast cells. €e rst induction cycle included Figure 1: Timeframe regarding diagnosis and treatment of patient 1. cytarabine plus an anthracycline (idarubicin 12 mg/m once €e gure presents the main treatment features and therapeutic daily on days 1–3 and cytarabine 200 mg/m as daily contin- approaches in patient 1. uous infusion on days 1–7). However, he had persistent leu- kemic blasts in the bone marrow 16 days after start of this cycle; additional treatment with cytarabine and idarubicin (idar- Relapsed disease was diagnosed 24 months after the rst ubicin 12 mg/m once daily on days 1 and 2; cytarabine treatment was completed; at the time of relapse, she was 200 mg/m as daily continuous infusion on days 1–5) was pregnant in the 28th week and she was induced for labor in the started the next day. He now reached a complete hematological 29th week. Cytogenetic analysis detected the original t(7;11) remission and received consolidation with another cycle of translocation in 6 out of 14 metaphases, and additional t(12;17) cytarabine plus idarubicin (5 + 2 regimen) and thereafter one with a translocation between chromosome 12p11 and 17q11 cycle of high-dose cytarabine. €e patient proceeded to allo- was also detected together with loss of the derivative chro- SCT with myeloablative conditioning based on busulfan plus mosome 17. €e latter abnormality leads to the loss of genes on cyclophosphamide with an HLA-matched sibling donor. 21 17p including the p53 gene. €e immunophenotypic features months after the transplantation, he presented with increased were similar as at initial diagnosis. New induction treatment liver enzymes and histological changes in his oral cavity was performed by idarubicin 12 mg/m once daily on days 1–3 con rmed by biopsy to be chronic GVHD (cGVHD). €irty- and cytarabine 200 mg/m as daily continuous infusion on nine months after allo-SCT, he presented with symptoms from days 1–7, and again she reached complete hematological re- his left ear, and he was diagnosed with an epipharyngeal tumor; mission after one induction cycle. €en she was given further biopsies from this lesion demonstrated tumor of myeloid origin consolidation therapy with one cycle of amsakrin 150 mg/m (Figure 4). €e tumor cells stained negative for CD56 with once daily on days 1–5, etoposide 110 mg/m once daily on immunohistochemistry. His bone marrow showed normal days 1–5, and cytarabine 200 mg/m as daily continuous in- cellularity with no signs of leukemia. €us, he had MS as the fusion on days 1–5. After this, she proceeded to myeloablative only manifestation of posttransplant AML relapse. He received conditioning (MAC) allo-SCT with a matched sibling donor. induction treatment with amsakrin 150 mg/m once daily on She showed no sign of GVHD at any time after the trans- days 1–5, etoposide 110 mg/m once daily on days 1–5, and plantation, and she achieved full donor chimerism. cytarabine 200 mg/m as daily continuous infusion on days She presented with a tumor in her left breast 62 months 1–5; peripheral blood and bone marrow examination were after the allo-SCT, and biopsy con rmed the diagnosis of consistent with complete hematological remission, and MRI myeloid sarcoma (Figure 2). Immunophenotypic features showed regress of the epipharyngeal tumor. €e consolidation were compatible with AML clone found at diagnosis and rst treatment was radiotherapy with 2 Gy × 20 (totally 40 Gy). relapse, although CD56 was dim positive. Positron emission After this treatment, he developed mucosal skin lesions in tomography (PET) scan showed increased uptake in the mouth consistent with cGVHD; for this reason, he never re- tumor as well as two smaller lesions in the right breast. Bone ceived DLI. MRI taken after completion of radiotherapy marrow examination showed no evidence of AML by mor- showed total regress of the tumor. He is still in complete re- phological and šow cytometric examination. She received mission 72 months after the diagnosis of relapse. induction treatment by idarubicin 12 mg/m once daily on days 1–3 and cytarabine 200 mg/m as daily continuous in- fusion on days 1–7. Control PET examination after one in- 3. Discussion duction cycle showed complete regression of šuorodeoxyglucose (FDG) uptake in the left breast. €e patient denied further MS is a tumor of immature myeloid cells located at an intensive chemotherapy and retransplantation. She therefore extramedullary (EM) site; it can develop in any organ or site in received consolidation treatment by radiation therapy the body but is more common at the immunological sanc- 2 Gy × 15 (total dose 30 Gy) against both breasts. In addition, tuary sites of the testis, ovary, and central nervous system she received three donor lymphocyte infusions (DLIs) in total (CNS) [2, 3]. Results from a multicenter survey implies skin 1.6 ×10 cells/kg; G-CSF-primed cells harvested at the time of and lymph nodes as frequently involved in de novo MS, stem cell harvesting were used for all three DLIs. After the last whereas soft tissues are more often involved in secondary MS DLI, she presented with oral and skin manifestations con- [3]. €e involvement of breast is uncommon [4], although sistent with GVHD and this diagnosis was con rmed with reported with relapsed disease [5]. €us, both our patients biopsy/histology. She has now been in complete remission with posttransplant MS had uncommon localizations. Case Reports in Oncological Medicine 3 (b) (a) (c) Figure 2: Stained biopsy from patient 1. (a) Histologic image (hematoxylin/eosin staining) of the breast biopsy showing a di¨use in ltrate of tumor cells with scant cytoplasm and large nuclei with “open” chromatin pattern and distinct nucleoli, consistent with blasts. €e blasts in ltrate around small residual acini (black arrows) in a lobule (white arrow). (b) €e tumor cells are myeloperoxidase positive by immunohistochemistry. (c) Dim to moderate positivity by immunohistochemical staining for CD56. Size bars: 80 μm. An EM AML relapse will usually progress to involve Induction (7 + 3) Radiotherapy other EM sites as well as the bone marrow within one year Induction II (5 + 2) Induction (MAE) [2]. €e incidence of EM AML relapse after allo-SCTof AML Consolidation (5 + 2) was 0.65% in a large retrospective study from the European Consolidation (cytarabine) Group of Blood and Marrow Transplantation (EBMT) [6]. Allo-SCT However, recent studies indicate that the incidence is higher, y0 y1 y2 y3 and posttransplant EM relapse has been described in 5–12% of allotransplanted AML patients, accounting for 7–46% of AML Chronic GVHD Myeloid all AML relapses [2, 7, 8]. Among longtime survivals, the sarcoma incidence has been reported to be as high as 20% [2, 9], and Figure 3: Timeframe regarding diagnostic and treatment of patient 2. EM relapse has been described until several years after €e gure presents the main treatment features and therapeutic transplantation [2, 5]. €e diagnosis is often delayed and the approaches in patient 2. relapse is usually diagnosed when it becomes symptomatic, because no standardized strategy for the surveillance to detect posttransplant EM relapse exists [7]. Measurable It is believed that the general immune-mediated anti- residual disease (MRD), either by multiparameter šow leukemic reactivity mediated by the general graft versus host cytometry or by genetic molecular markers, is established as reactivity that is associated with the occurrence of GVHD an independent prognostic marker in AML [10]. However, preferentially maintains bone marrow remission but does the methodology of these approaches has currently not been not prevent EM relapse [8]. €e occurrence of acute GVHD qualitatively or quantitatively standardized, making their use (aGVHD) is signi cantly associated with better bone mar- in clinical practice challenging [10], and none of our patients row relapse-free survival; however, the EM relapse rate for was followed by MRD monitoring. Furthermore, if detecting patients with or without a GVHD seems to be similar [7]. €ere are several possible explanations for this phenome- of MRD could proceed, diagnosis of EM AML relapse re- mains elusive, although should be further investigated in non. Firstly, AML cells in peripheral tissues may evade upcoming clinical trials. immune surveillance [2], as the number of e¨ector cells for €e best treatment of isolated EM relapse after allo-SCT immune-mediated antileukemic reactivity is higher in the is unknown [8, 11]. Previous induction and conditioning bone marrow. €e partial loss of several human leukocyte treatment causing cumulative toxicities and high-dose antigen (HLA) class I genes may further decrease the general chemotherapy with suppression of the graft versus leuke- e§ciency of the antileukemic immune reactivity [7]. Sec- mia (GVL) reactivity have to be considered when deciding ondly, the CD56 expression in AML cells mediates cell-cell a therapeutic strategy with su§cient antileukemic e§ciency adhesion and is highly expressed in various tissues; these versus the risk of severe and unacceptable toxicity [8, 11]. €e adhesion molecules seem to be involved in EM homing and prognosis of solitary EM relapse remains poor, although it may then support EM AML cell survival [7]. It has been suggested that the CD56 cell surface expression together with seems slightly better than bone marrow relapse alone or combined bone marrow and EM relapse [7]. the encoded fusion proteins in patients with the chromosomal 4 Case Reports in Oncological Medicine (b) (a) (c) Figure 4: Stained biopsy from patient 2. (a) Subepithelial di¨use in ltrate of blasts in the biopsy specimen from the epipharyngeal lesion (hematoxylin/eosin staining). Black arrow: respiratory epithelium. (b) Virtually all the blasts are myeloperoxidase positive by immu- nohistochemistry. (c) €e tumor cells are negative for CD56. Size bars: 80 μm. prognosis [3], and treatment approaches for EM relapse after abnormalities t(8:21) and inv(16) is associated with EM AML cell in ltration [7], although it is unknown whether these allo-SCT should probably involve combination of local and systemic therapy to prevent systemic relapse [7, 16]. mechanisms are important for posttransplant EM relapse [7]. EM presentation has also been associated with other Treatment options for patients with EM relapse should chromosomal abnormalities like trisomy of chromosomes 4, be considered individually [17]. Since radiological exami- 8, and 11 as well as deletion of chromosomes 5q, 16q, and 20q nation after induction treatment did not reveal disease ac- [12]. Noteworthy, the myoblast for one of our patients was tivity in the breasts for our rst patient, further surgery was only dim positive for CD56 in the biopsy of the relapsed EM therefore not performed. DLI is regarded as an e¨ective AML in the breast, and for the other patient only 3% of the treatment of posttransplant bone marrow relapse, although blast cells at the time of AML diagnosis was CD56 positive. may not be equally e¨ective for EM relapse [2, 18]. However, €irdly, some studies suggest that EM relapse is higher after the combination of DLI with chemotherapy will often make it di§cult to di¨erentiate the e¨ects of the immunotherapy allo-SCT compared to auto-SCT and that the incidence of MS relapse seems to be increased after DLI and in and the chemotherapy [2]. Only one of our patients received DLI, although discontinued after three infusions because of retransplanted patients [7, 13–15]. Other factors associated with increased risk of EM after allotransplantation are re- GVHD. €e curative e¨ect of allo-SCT in AML is considered lapsed or refractory disease at time of transplant, unfavorable to be due to a combined e¨ect of conditioning chemotherapy cytogenetics, EM disease before allo-SCT, retransplantation, and posttransplant immune-mediated antileukemic activity, age below 18 years, and FAB subtypes M4/M5 [7, 12]. Finally, and for this reason it is probably important to maintain this if certain pretransplant conditioning regimens are more ef- immune reactivity in patients with EM relapse [8]. fective with regard to prevention of posttransplant EM relapse A possible treatment for isolated EM relapse is is unknown [7]. None of these risk factors were present in our gemtuzumab/ozogamicin (GO), acting by depleting CD33- patients. Both patients were in complete hematological re- expressing leukemic cells and possible bolstering antileu- kemic immune reactivity [8, 19]. €e risk of severe toxicity mission at the time of transplantation, they received busulfan- based conditioning, and one of them had clinical signs of and especially hepatic injury with veno-occlusive disease GVHD before EM relapse was diagnosed. (VOD) should be taken into account [8]. Another systemic €ere are no established guidelines for the treatment of active agent that does not abrogate the antileukemic immune EM relapse after allo-SCT. €e common practice is a com- reactivity is the hypomethylating agents 5-azacitidine and bination of local and systemic treatment including intensive decitabine, which even might enhance the GVL e¨ect. €ese chemotherapy, local radiotherapy, DLI, and/or retrans- agents induce AML cell di¨erentiation and increase the ex- plantation [2, 9]. Anti-AML therapy seems to be e¨ective in pression of HLA antigens as well as tumor-associated antigens patients presenting with MS alone [1], and systemic che- [7]; this strategy is used for the treatment of posttransplant motherapy is required rather than surgery or radiotherapy bone marrow relapse of both AML and myelodysplastic alone to prevent relapse and disease progression. However, syndromes (MDS) [7, 9]. Case reports suggest that these agents may be e¨ective even for patients with posttransplant many of these previous studies do not di¨erentiate between de novo and secondary MS with regard to treatment and EM and previous treatment failure after DLI, radiotherapy, Case Reports in Oncological Medicine 5 Group for Blood and Marrow Transplantation,” Bone Marrow and intensive chemotherapy [9, 20]. Finally, CD56 expres- Transplantation, vol. 17, no. 5, pp. 801–808, 1996. sion in leukemic cells and antibodies conjugated with a [7] S. Yoshihara, T. Ando, and H. Ogawa, “Extramedullary re- toxin or a radioisotope may represent future strategies for lapse of acute myeloid leukemia after allogeneic hemato- the treatment of these patients [7]. poietic stem cell transplantation: an easily overlooked but significant pattern of relapse,” Biology of Blood and Marrow 4. Conclusion Transplantation, vol. 18, no. 12, pp. 1800–1807, 2012. [8] T. Ando, N. Mitani, K. Matsunaga et al., “Gemtuzumab EM posttransplant AML relapse may be more common ozogamicin therapy for isolated extramedullary AML relapse than previously assumed, and its prognosis remains poor after allogeneic hematopoietic stem-cell transplantation,” even though possibly slightly better than for combined EM Tohoku Journal of Experimental Medicine, vol. 220, no. 2, and bone marrow relapse or bone marrow relapse alone. pp. 121–126, 2010. [9] A. Antar, Z. K. Otrock, M. Kharfan-Dabaja et al., “Azacitidine No guidelines for standard treatment of these patients are in the treatment of extramedullary relapse of AML after al- available, but a common practice is systemic chemotherapy logeneic hematopoietic cell transplantation,” Bone Marrow or immunotherapy (i.e., DLI or retransplantation) com- Transplantation, vol. 48, no. 7, pp. 994-995, 2013. bined with local radiotherapy. Cumulative toxicities due to [10] G. J. Schuurhuis, M. Heuser, S. Freeman et al., “Minimal/ previous chemotherapy and the risk of suppressing clini- measurable residual disease in AML: consensus document cally relevant antileukemic immune reactivity have to be from ELN MRD Working Party,” Blood, 2018, In press. considered when the treatment of such patients is decided. [11] Y. Koc, K. B. Miller, D. P. Schenkein, P. Daoust, K. Sprague, Our two patients received intensive chemotherapy in- and E. Berkman, “Extramedullary tumors of myeloid blasts in duction followed by consolidating radiotherapy, and only adults as a pattern of relapse following allogeneic bone one of them received DLI; both patients are still alive marrow transplantation,” Cancer, vol. 85, no. 3, pp. 608–615, without relapse. Future studies should focus on the de- 1999. [12] M. Solh, S. Solomon, L. Morris, K. Holland, and A. Bashey, velopment of diagnostic strategies for earlier detection of “Extramedullary acute myelogenous leukemia,” Blood Re- EM relapse and the identification of molecular mechanisms views, vol. 30, no. 5, pp. 333–339, 2016. (i.e., possible therapeutic targets) behind EM homing of [13] S. J. Choi, J. H. Lee, J. H. Lee et al., “Treatment of relapsed leukemic cells. acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF- Conflicts of Interest primed donor leukocyte infusion: a high incidence of iso- lated extramedullary relapse,” Leukemia, vol. 18, no. 11, ,e authors declare that they have no conflicts of interest. pp. 1789–1797, 2004. [14] S. Singhal, R. Powles, S. Kulkarni, J. Treleaven, R. Saso, and J. Mehta, “Long-term follow-up of relapsed acute leukemia Acknowledgments treated with immunotherapy after allogeneic transplantation: the inseparability of graft-versus-host disease and graft-versus- ,e study was supported by Øyvinn Mølbach-Pedersen’s leukemia, and the problem of extramedullary relapse,” Leu- Foundation, Helse Vest, and the Norwegian Cancer Society. kemia & Lymphoma, vol. 32, no. 5-6, pp. 505–512, 1999. [15] A. Takami, H. Okumura, H. Yamazaki et al., “Prospective trial References of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for [1] A. M. Tsimberidou, H. M. Kantarjian, S. Wen et al., “Myeloid relapsed leukemia after allogeneic stem cell transplantation,” sarcoma is associated with superior event-free survival and International Journal of Hematology, vol. 82, no. 5, pp. 449–455, overall survival compared with acute myeloid leukemia,” Cancer, vol. 113, no. 6, pp. 1370–1378, 2008. [16] M. Solh, T. E. DeFor, D. J. Weisdorf, and D. S. Kaufman, [2] W. B. Clark, S. A. Strickland, A. John Barrett, and B. N. Savani, “Extramedullary relapse of acute myelogenous leukemia after “Extramedullary relapses after allogeneic stem cell trans- allogeneic hematopoietic stem cell transplantation: better plantation for acute myeloid leukemia and myelodysplastic prognosis than systemic relapse,” Biology of Blood and syndrome,” Haematologica, vol. 95, no. 6, pp. 860–863, 2010. Marrow Transplantation, vol. 18, no. 1, pp. 106–112, 2012. [3] D. Lazzarotto, A. Candoni, C. Fil`ı et al., “Clinical outcome of [17] R. L. Bakst, M. S. Tallman, D. Douer, and J. Yahalom, “How I myeloid sarcoma in adult patients and effect of allogeneic treat extramedullary acute myeloid leukemia,” Blood, vol. 118, stem cell transplantation. Results from a multicenter survey,” no. 14, pp. 3785–3793, 2011. Leukemia Research, vol. 53, pp. 74–81, 2017. [18] C. Berthou, M. C. Leglise, A. Herry et al., “Extramedullary [4] X. E. Huang, Y. J. Li, and X. D. Zhou, “Granulocytic sarcoma relapse after favorable molecular response to donor leukocyte of the breast: a case report,” Oncology Letters, vol. 10, no. 4, infusions for recurring acute leukemia,” Leukemia, vol. 12, pp. 2447–2449, 2015. no. 11, pp. 1676–1681, 1998. [5] Y. Lou, W. Qian, H. Meng, Y. Tong, and J. Jin, “Frequent [19] T. Owonikoko, M. Agha, R. Balassanian, R. Smith, and extramedullary recurrence of isolated myeloid sarcoma in the A. Raptis, “Gemtuzumab therapy for isolated extramedullary long-term follow-up,” Annals of Hematology, vol. 91, no. 8, AML relapse following allogeneic stem-cell transplant,” Nature pp. 1317–1319, 2012. Clinical Practice Oncology, vol. 4, no. 8, pp. 491–495, 2007. [6] A. N. Bekassy, J. Hermans, N. C. Gorin, and A. Gratwohl, [20] E. Jabbour, S. Giralt, H. Kantarjian et al., “Low-dose azaci- “Granulocytic sarcoma after allogeneic bone marrow trans- tidine after allogeneic stem cell transplantation for acute plantation: a retrospective European multicenter survey. leukemia,” Cancer, vol. 115, no. 9, pp. 1899–1905, 2009. Acute and Chronic Leukemia Working Parties of the European MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

Journal

Case Reports in Oncological Medicine – Hindawi Publishing Corporation

Published: Feb 28, 2018

There are no references for this article.