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Low-Dose Decitabine for Patients With Letters RESEARCH LETTER the decitabine group vs 27.3% in the control group (P = .001). In the treatment group, platelet counts increased signifi- Low-Dose Decitabine for Patients With cantly 4 weeks after decitabine injections (Figure), with a Thrombocytopenia Following Allogeneic median time of 22 days to achieve platelet transfusion- Hematopoietic Stem Cell Transplantation: independence, and maintained until the sixth month, except A Pilot Therapeutic Study for the patient with minor response. Isolated thrombocytopenia after hematopoietic stem cell trans- In bone marrow morphological analysis, patients in both plantation (HSCT) is defined as consistently low platelet counts groups revealed low levels of megakaryocytes at week 0. How- after transplantation, with recovery of all other peripheral blood ever, the significantly increasing megakaryocyte level, espe- cell lines.1 It represents a challenging clinical problem be- cially the “platelet shedding” megakaryocyte, was observed cause it often leads to an increased risk of life-threatening hem- only in decitabine group at week 4 (Figure). Transplantation- orrhage, frequent requirement of platelet transfusions, and ex- related complications (eg, chronic GVHD), antiplatelet anti- tended hospital stays.2 Previous studies have demonstrated bodies, and T-cell subsets did not noticeably change after that decitabine, a hypomethylating agent, can increase plate- decitabine treatment. No clinically significant myelosuppres- let counts by enhancing platelet release and megakaryocyte sion, febrile neutropenia, or nonhematologic toxic effects were maturation in mice.3 Herein, we report a pilot study showing observed during the study period. efficacy of decitabine in patients with isolated thrombocyto- penia post-HSCT. Discussion | Our study shows a very encouraging result of decitabine in increasing peripheral platelets in HSCT recipi- Methods | An open-label study was designed to evaluate ents, with remarkably increased megakaryocyte counts. There decitabine treatment for isolated thrombocytopenia in allo- was no evident change in antiplatelet antibodies and T-cell sub- geneic HSCT patients with hematological malignant neo- types after decitabine administration, implying that decitabine plasms. The inclusion criteria were (1) primary or secondary functions independent of immune regulation. In mice, platelet count of 30 × 103/μL or less persistently at day 60 decitabine was found to induce megakaryocyte differentia- post-HSCT or later; (2) recovered neutrophil and hemoglo- tion and promote platelets release.3 This mechanism may have bin; (3) full donor chimerism; and (4) no response to conven- contributed to our results. tional therapies (eg, thrombopoietin, immunoglobulin, Myelosuppression is the main concern of decitabine. rituximab, plasma exchange alone or in combination) for a Low-dose decitabine could optimize clinical responses duration of at least 4 weeks. Patients with relapse of their with less toxic effects.5 Based on previous studies, we malignant disease, active infections, uncontrolled graft-vs- used 15 mg/m2 for 3 days, which was well tolerated by the host disease (GVHD), severe organ damage, or transplant- participants. related thrombosis were excluded. Enrolled patients were Although the sample size of this study is small, with a distributed into either the control group to receive the con- relatively short follow-up, the clinically significant platelet ventional therapies or the treatment group to receive addi- recovery following decitabine treatment suggest potentially tional decitabine (15 mg/m2 daily intravenously for 3 con- important clinical benefits and warrant the necessity for a secutive days) in random. All participants provided written large-scale clinical trial of this promising therapy. informed consent in accordance with the Declaration of Hel- sinki, and the study protocol was approved by the ethics Yue Han, MD, PhD committee of The First Affiliated Hospital of Soochow Uni- Yaqiong Tang, MD versity, Suzhou, China. Jia Chen, MD Peripheral blood cell counts, virology, antiplatelet anti- Jianying Liang, MD bodies, and T-cell subsets were analyzed routinely. Bone mar- Chunmei Ye, MD row puncture was performed before treatment (week 0) and Changgeng Ruan, MD, PhD then repeated at week 4. Platelet responses were evaluated ac- Depei Wu, MD, PhD cording to an international working group guideline within a 4 8-week study period. Author Affiliations: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital Results | From July 2013 through February 2014 at our hospi- of Soochow University, Suzhou, China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. tal, 251 patients received allogeneic HSCT, and 72 of them de- veloped isolated thrombocytopenia afterward. During this pe- Corresponding Author: Depei Wu, MD, PhD, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First riod, 22 patients (Table) were enrolled in this study based on Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu the criteria described herein. The response rate was 100% in Province, China 215006 ([email protected]). jamaoncology.com (Reprinted) JAMA Oncology May 2015 Volume 1, Number 2 249 Copyright 2015 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Letters Table. Clinical and Laboratory Characteristics of Patients in 2 Groups Platelet Count, MK Count, MK Morphology Patient No./ ×103/μL per Smear (GMK/PMK/NMK) Sex/ Transplant Age, y Disease Typea Post-HSCT, d Previous Therapy Wk 0 Wk 4 Wk 8 Wk 0 Wk 4 Wk 0 Wk 4 Response Control Group 1/F/34 NHL MMRD 97 Thrombopoietin, 300 U/kg/d; 13 18 7 1 0 1/0/0 0/0/0 No prednisone, 1 mg/kg/d 2/M/28 AML MRD 63 Thrombopoietin, 300 U/kg/d; 13 7 9 6 7 3/1/2 3/1/2 No prednisone, 1 mg/kg/d 3/F/36 ALL MMRD 95 Thrombopoietin, 300 U/kg/d; 5 21 28 4 19 2/0/1 9/2/5 Minor prednisone, 1 mg/kg/d 4/F/16 ALL MMRD 160 Thrombopoietin, 300 U/kg/d; 12 8 Death 8 5 4/1/2 2/0/2 No prednisone, 1 mg/kg/d; immunoglobulin, 400 mg/kg/d ×5 d 5/M/31 ALL MMRD 62 Thrombopoietin, 300 U/kg/d; 10 19 55 6 22 3/0/1 12/1/9 Major prednisone, 1 mg/kg/d 6/M/18 ALL MUD 186 Thrombopoietin, 300 U/kg/d; P 13 10 7 0 1 0/0/0 1/0/0 No 7/M/23 CMML MMRD 112 Thrombopoietin, 300 U/kg/d; 15 43 22 2 54 2/0/0 30/13/10 Major prednisone, 1 mg/kg/d 8/M/28 AML MMRD 120 Thrombopoietin, 300 U/kg/d; 22 10 18 16 17 8/1/4 10/0/5 No prednisone, 1 mg/kg/d; immunoglobulin, 400 mg/kg/d ×5 d 9/F/51 AML MRD 131 Thrombopoietin, 300 U/kg/d; P; 4 11 14 33 7 27/1/4 4/0/1 No prednisone, 1 mg/kg/d 10/M/25 ALL MMRD 129 Thrombopoietin, 300 U/kg/d; 13 8 21 29 13 15/2/10 8/0/4 No prednisone, 1 mg/kg/d 11/F/51 NHL MRD 65 Thrombopoietin, 300 U/kg/d; 14 9 17 18 4 10/2/4 2/0/0 No prednisone, 1 mg/kg/d Decitabine Group 1/F/36 AML MRD 76 Thrombopoietin, 300 U/kg/d; 12 60 72 20 52 9/1/10 34/3/15 Major immunoglobulin, 400 mg/kg/d ×5 d; prednisone, 1 mg/kg/d 2/F/46 ALL MMRD 65 Thrombopoietin, 300 U/kg/d ; 16 35 55 15 51 11/1/1 44/1/6 Major prednisone, 1 mg/kg/d 3/F/22 MDS MMRD 62 Thrombopoietin, 300 U/kg/d; 17 70 78 8 133 6/0/1 92/28/13 Major prednisone, 1 mg/kg/d 4/F/37 AML MRD 211 Thrombopoietin, 300 U/kg/d; 13 65 72 10 127 7/0/2 88/23/14 Major prednisone, 1 mg/kg/d 5/M/8 ALL MMRD 97 Thrombopoietin, 300 U/kg/d; 18 37 35 5 30 4/0/1 22/3/4 Major prednisone, 1 mg/kg/d 6/F/57 AML MUD 138 Thrombopoietin, 300 U/kg/d; 30 90 82 15 24 12/1/2 18/1/5 Major prednisone, 1 mg/kg/d 7/M/32 MDS MMRD 84 Thrombopoietin, 300 U/kg/d; 18 45 67 12 129 7/0/4 106/5/5 Major prednisone, 1 mg/kg/d 8/M/43 MDS MMRD 99 Thrombopoietin, 300 U/kg/d; 12 97 140 17 105 10/0/7 80/10/8 Major rituximab, 375 mg/m2;P; immunoglobulin, 400 mg/kg/d ×5 d 9/M/34 AML MMRD 63 Thrombopoietin, 300 U/kg/d; 10 124 163 0 128 0/0/0 105/5/10 Major prednisone, 1 mg/kg/d 10/F/52 NHL MRD 196 Thrombopoietin, 300 U/kg/d; 8 28 26 2 0 1/0/0 0/0/0 Minor prednisone, 1 mg/kg/d 11/M/37 AML MRD 472 Thrombopoietin, 300 U/kg/d; P; 11 115 203 5 17 3/0/1 9/1/5 Major prednisone, 1 mg/kg/d Abbreviations: ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; a Transplant type of MMRD and MUD, conditioning regimen (with T-cell CMML, chronic myelomonocytic leukemia; ); GMK, granular megakaryocyte; depletion): antithymocyte globulin (ATG) + busulfan-cyclophosphamide GVHD, graft-vs-host disease; HSCT, hematopoietic stem cell transplantation; (BUCY); GVHD prophylaxis: cyclosporinA, methotrexate, and mycophenolate MDS, myelodyplastic syndrome; MK, megakaryocyte; MMRD, mismatched mofetil. Transplant type of MRD, conditioning regimen (without T-cell related donor; MRD, matched related donor; MUD, matched unrelated donor; depletion): BUCY. GVHD prophylaxis: cyclosporinA and methotrexate. NHL, non-Hodgkin lymphoma; NMK, naked nuclear megakaryocyte; P, plasma exchange; PMK, platelet-shedding megakaryocyte.
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