Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities

TL Gindina, NN Mamaev, SN Bondarenko, ES Nikolaeva, IA Petrova, OA Slesarchuk, AS Borovkova, SV Razumova, AL Alyanskii, LS Zubarovskaya, BV Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Gindina TL, Mamaev NN, Bondarenko SN, et al. Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities. Clinical oncohematology. 2016;9(3):271-78(In Russ).

DOI: 10.21320/2500-2139-2016-9-3-271-278


ABSTRACT

Aim. To evaluate the prognostic significance of the complex karyotype including del(5q), –7, del(7q) abnormalities in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. Forty-four AML patients with chromosome 5 and/or 7 abnormalities (22 women and 22 men, aged from 1.2 to 67 years, median 31.2 years) were examined. Analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed.

Results. Prior to allo-HSCT, the complex karyotype (with three or more chromosomal abnormalities) was observed in 19 (43 %) patients, the monosomal karyotype was in 8 (18 %) patients. Univariate analysis demonstrated that OS and EFS differed in patients from different age groups (³ 18 vs. < 18 years; = 0.01 and = 0.05, respectively), with different disease status at transplantation (1 remission vs. other clinical status; = 0.1 and = 0.008, respectively), with and without complex karyotype (СK– vs. CK+; = 0.05 and = 0.002, respectively), with and without monosomal karyotype (МK– vs. MK+; = 0.009, only for EFS), and with different stem cells source (bone marrow vs. other source; = 0.03 only for OS). Multivariate analysis confirmed that age of 18 years and more (= 0.02 and = 0.01, respectively), active disease at allo-HSCT (= 0.04 and = 0.005, respectively), complex karyotype (= 0.04 и = 0.0008, respectively) and stem cell source other than bone marrow (= 0.02 only for OS) were independent predictors of OS and EFS deterioration.

Conclusion. The study demonstrates that chromosome 5 and/or 7 abnormalities as a part of the complex karyotype is high-risk factor in AML patients undergoing allo-HSCT (unlike the monosomal karyotype), that requires the special therapeutic approach.


Keywords: acute myeloid leukemias, complex karyotype, chromosome 5 and 7 abnormalities, allogeneic hematopoietic stem cell transplantation, prognosis.

Received: March 5, 2016

Accepted: April 5, 2016

Read in PDF (RUS)pdficon


REFERENCES

  1. Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74. doi: 10.1182/blood-2009-07-
  2. Breems DA, Van Putten WL, De Greef GE, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26(29);4791–7. doi: 10.1200/jco.2008.16.0259.
  3. Medeiros BC, Othus M, Fang M, et al. Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience. Blood. 2012;116(13):2224–8. doi: 10.1182/blood-2010-02-
  4. Fang M, Storer B, Estey E, et al. Outcome of patients with acute myeloid leukemia with monosomal karyotype who undergo hematopoietic cell transplantation. Blood. 2011;118(6):1490–4. doi: 10.1182/blood-2011-02-
  5. Lazarus HM, Litzow MR. AML cytogenetics: the complex just got simpler. Blood. 2012;120(12):2357–8. doi: 10.1182/blood-2012-08-
  6. Kayzer S, Zucknick M, Dohner K, et al. Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood. 2011;119(2):551–8. doi: 10.1182/blood-2011-07-
  7. Voutiadou G, Papaioannou G, Gaitatzi M, et al. Monosomal karyotype in acute myeloid leukemia defines a distinct subgroup within the adverse cytogenetic risk category. Cancer Genet. 2013;206(1–2):32–6. doi: 10.1016/j.cancergen.2012.10.003.
  8. Guo RJ, Atenafu EG, Craddock K, et al. Allogeneic hematopoietic cell transplantation may alleviate the negative prognostic impact of monosomal and complex karyotypes on patients with acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20(5):690–5. doi: 10.1016/j.bbmt.2014.01.027.
  9. Cornelissen JJ, Breems D, Putten WLJ, et al. Comparative analysis of the value of allogeneic hematopoietic stem-cell transplantation in acute myeloid leukemia with monosomal karyotype versus other cytogenetic risk categories. J Clin Oncol. 2012;30(17):2140–6. doi: 10.1200/jco.2011.39.6499.
  10. Hemmati P, Schuzle-Luckow A, Terwey T, et al. Cytogenetic risk grouping by the monosomal karyotype classification is superior in predicting the outcome of acute myeloid leukemia undergoing allogeneic stem cell transplantation in complete remission. Eur J Haematol. 2013;92(2):102–10. doi: 10.1111/ejh.12216.
  11. Гиндина Т.Л., Мамаев Н.Н., Бархатов И.М. и др. Сложные повреждения хромосом у больных с рецидивами острых лейкозов после аллогенной трансплантации гемопоэтических стволовых клеток. Терапевтический архив. 2012;84(8):61–6. [Gindina TL, Mamaev NN, Barhatov IM, et al. Complex chromosome damages in patients with recurrent acute leukemias after allogeneic hematopoietic stem cell transplantations. Terapevticheskii arkhiv. 2012;84(8):61–6. (In Russ)]
  12. Schaffer L, McGovan-Jordan J, Schmid M. ISCN. An international System for Human Cytogenetic Nomenclature. Basel: S. Karger; 2013. pp. 140.
  13. Wawrzyniak E, Wierzbowska A, Kotkowska A, et al. Different prognosis of acute myeloid leukemia harboring monosomal karyotype with total or partial monosomies determined by FISH: Retrospective PALG study. Leuk Res. 2013;37(3):293–9. doi: 10.1016/j.leukres.2012.10.022.
  14. Yoon JH, Kim HJ, Shin SH, et al. Stratification of de novo adult acute myelogenous leukemia with adverse-risk karyotype: can we overcome the worse prognosis of adverse-risk group acute myelogenous leukemia with hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(1):80–8. doi: 10.1016/j.bbmt.2013.10.015.

Complex Karyotype in Pediatric Acute Myeloid Leukemia

EV Fleishman1, OI Sokova1, AV Popa1, II Kalinina2, LN Konstantinova1

1 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology under the Ministry of Health of the Russian Federation, 1 Samory Mashela str., Moscow, Russian Federation, 117997

For correspondence: Elena Vol’fovna Fleischman, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)323-57-22; e-mail: flesok@yandex.ru

For citation: Fleishman EV, Sokova OI, Popa AV, et al. Complex Karyotype in Pediatric Acute Myeloid Leukemia. Clinical oncohematology. 2015;8(2):151–60 (In Russ).


ABSTRACT

Objective. To evaluate the clinical relevance of the complex karyotype in pediatric practice.

Methods. In this study, we investigated the karyotype of 521 patients with de novo AML (299 children and 222 adults). Among them 34 pediatric patients and 25 adults had various complex karyotypes.

Results. Certain differences of complex karyotypes between pediatric and adult AML were revealed. Some peculiarities of marker sets were also found: in children, such high-risk markers as monosomy 5 and del(5q) as well as monosomy 7 and del(7q) were less frequent than in adults. Monosomal complex karyotypes were less common in children. Specific distribution of blast cell morphological types was observed in pediatric AML with complex karyotypes. Unlike AML with noncomplex karyotype, where the M2 type was found in almost a half (47.9 %) of patients, in patients with 3 and more chromosome aberrations its incidence was 11.8 % only (= 0,000). However, incidence of M5 and rare M0 and M7 types in patients with complex karyotype was higher than in the others. RFS in patients with a complex karyotype was similar to that of remaining patients in the high-risk group: 38.4 ± 9.9 % and 30.6 ± 8.8 %, respectively. The OS rate of patients with a complex karyotype was practically identical to that of intermediate-risk group patients: 48.0 ± 10.0 % and 48.0 ± 10.0 %, respectively. There was a comparatively high 10-year survival rate (RFS and OS were higher than 30 %) in the pediatric high-risk group. Ten of 25 (40 %) patients with complex karyotype survived five years and 7 of them persisted in complete remission for more than 10 years. Five-year survival in adults from high-risk group is up to 15 %.

Conclusion. Analysis of data on survival of pediatric AML does not answer a question in which prognostic group (high or intermediate-risk) cases of AML with complex karyotypes without high-risk chromosome markers must be included.

Keywords: pediatric acute myeloid leukemia, chromosome aberrations, complex karyotype.


Received: November 26, 2014

Accepted: February 2, 2015

Read in PDF (RUS)pdficon


REFERENCES

  1. Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML10 trial. Blood. 1998;92(7):2322–33.
  2. Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100(13):4325–36. doi: 10.1182/blood-2002-03-0772.
  3. Mitelman F. Catalog of chromosome aberrations in cancer. 5th edition. Willey-Liss; 1995.
  4. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  5. Grimwade D. The changing paradigm of prognostic factors in acute myeloid leukemia. Best Pract Res Clin Haematol. 2012;25(4):419–25. doi: 10.1016/j.beha.2012.10.004.
  6. Mrozek K. Acute myeloid leukemia with a complex karyotype. Semin Oncol. 2013;35(4):365–77. doi: 10.1053/j.seminoncol.2008.04.007.
  7. Creutzig U, van den Heuvel-Eibrink MM, Gibson B, et al. Diagnosis and management of acute myeloid leukemia in children and adolescents; recommendations from an international expert panel. Blood. 2012;120(16):3187–205. doi: 10.1182/blood-2012-03-362608.
  8. von Neuhoff C, Reinhardt D, Sander A, et al. Prognostic impact of specific chromosomal aberrations in large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol. 2010;28(16):2682–8. doi: 10.1200/jco.2009.25.6321.
  9. Harrison CJ, Hills RK, Moorman AV, et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML10 and 12. J Clin Oncol. 2010;28(16):2674–81. doi: 10.1200/jco.2009.24.8997.
  10. Флейшман Е.В., Сокова О.И., Кириченко О.П. и др. Сложные аномалии кариотипа при остром миелоидном лейкозе детей. Вестник РАМН. 2008;5:3–7. [Fleishman EV, Sokova OI, Kirichenko OP, et al. Complex karyotype abnormalities in pediatric acute myeloid leukemia. Vestnik RAMN. 2008;5:3–7. (In Russ)]
  11. Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United kingdom Medical Research Council trials. Blood. 2010;116(3):354–65. doi: 10.1182/blood-2009-11-254441.
  12. Баранова О.Ю., Волкова М.А., Френкель М.А. и др. Анализ результатов различных программ терапии острых нелимфобластных лейкозов с М0-М2, М4-М7 ФАБ-вариантами (по данным Российского онкологического научного центра им. Н.Н. Блохина, РАМН). Гематология и трансфузиология. 2003;48(2):3–10. [Baranova OYu, Volkova MA, Frenkel’ MA, et al. Analysis of outcomes of different treatment regimens for acute non-lymphoblastic leukaemia with M0-M2, M4-M7 FAB-variants (according to data of the N.N. Blokhin Russian Cancer Research Center). Gematologiya i transfuziologiya. 2003;48(2):3–10. (In Russ)]
  13. Shaffer LG, et al, eds. ISCN-2013: An International System for Human Cytogenetic Nomenclature. Basel: Karger; 2013.
  14. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457–81. doi: 10.2307/2281868.
  15. Stark B, Jeison M, Glazer G, et al. Classical and molecular cytogenetic abnormalities and outcome of childhood acute myeloid leukemia: a report from a referral center in Israel. Br J Haematol. 2004;126(3):320–37. doi: 10.1111/j.1365-2141.2004.05038.x.
  16. Gibson BES, Webb DKH, Howman AJ, et al. Results of randomized trial in children with acute myeloid leukemia: Medical research Council AML 12 trial. Br J Haematol. 2011;155(3):366–77. doi: 10.1111/j.1365-2141.2011.08851.x.
  17. Kelly MG, Horan JT, Alonzo TA, et al. Comparable survival for pediatric acute myeloid leukemia with poor-risk cytogenetics following chemotherapy, matched related donor, or unrelated donor transplantation. Pediatr Blood Cancer. 2014;61(2):269–375. doi: 10.1002/pbc.24739.
  18. Slovak ML, Kopecku KJ, Kassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology group study. Blood. 2000;96(13):4075–83.
  19. Schoch C, Haferlach T, Haase D, et al. Patients with de novo acute myeloid leukemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients. Br J Haematol. 2001;112(1):118–26. doi: 10.1046/j.1365-2141.2001.02511.x.
  20. Schoch C, Kern W, Schnittger S, et al. The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. Haematologica. 2004;89(9):1082–90.
  21. Breems DA, van Putten DL, de Greef GE, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26(29):4791–7. doi: 10.1200/jco.2008.16.0259.

Complex Chromosomal Aberrations in Patients with Post-Transplantation Relapses of Acute Leukemias: Clinical and Theoretical Aspects

TL Gindina, NN Mamaev, SN Bondarenko, NV Semenova, EN Nikolaeva, ME Vlasova, NV Stancheva, OA Slesarchuk, VN Vavilov, EV Morozova, AL Alyanskii, BV Afanasev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: tatgindina@gmail.com

For citation: Gindina TL, Mamaev NN, Bondarenko SN, et al. Complex Chromosomal Aberrations in Patients with Post-Transplantation Relapses of Acute Leukemias: Clinical and Theoretical Aspects. Clinical oncohematology. 2015;8(1):69–77 (In Russ).


ABSTRACT

Objective. To analyze the incidence of a complex karyotype in patients with post-transplantation relapses of acute myeloid leukemias and to evaluate preliminary treatment results before and after bone marrow transplantation in order to elaborate optimal approaches to the treatment of this disease.

Methods. Cytogenetic investigations (including fluorescent in situ hybridization [FISH]) were performed in 100 patients (53 males, 47 females aged from 1 to 60; median — 23 years) with post-transplantation relapses of acute myeloid leukemias (AML) (n = 61) and acute lymphoblastic leukemia (ALL) (n = 39).

Results. Aberrant karyotypes were found in 90 % of AML and 97 % of ALL patients. The incidence of acute leukemias (AL) with complex karyotypes (CK) was significantly higher in ALL patients than that in the AML group (67 % vs 36 %; = 0.002). At that, the percentage of CK with 4 and more chromosome abnormalities per cell in ALL patients aged 1–18 years was also significantly higher than that in AML patients (60 % vs 30 %; = 0.03). Besides, this difference was observed in the CK+ proportion between ALL and AML groups. Transplantation was performed during the active phase of the disease (i.e. after remission) in 75 % vs 55 %, respectively (= 0.003).

Conclusions. Serial cytogenetic investigations showed that CKs before transplantation and in PTR are closely related, thus confirming their clonal nature. Therefore, it may be assumed that karyotype complication achieved by the PTR can be caused by both chemotherapy performed at early stages of acute leukemia and pre-transplant conditioning regimes. In this case, further increase of the chemotherapeutic intensity in order to prevent and treat expected PTRs in patients with CK+ acute leukemias seems to be unreasonable. In this connection, infusion of donor lymphocytes, administration of hypomethylating agents or medicines with target mechanism of action should be used for management of AML patients during the post-transplant period.


Keywords: acute leukemias, post-transplantation relapses, complex karyotype.

Received: September 2, 2014

Accepted: November 13, 2014

Read in PDF (RUS)pdficon


REFERENCES

  1. Dobbelstein C, Dammann E, Weissinger E, et al. Prognostic impact of a newly defined structurally complex karyotype in patients with AML and MDS after allogeneic stem cell transplantation. Blood (ASH Annual Meeting Abstracts). 2013;122(21):3362–3.
  2. Mohr B, Stolzel F, Kramer M, et al. Karyotypic complexity in acute myeloid leukemia in the context of adverse prognosis. Blood (ASH Annual Meeting Abstracts). 2013;122(21):489.
  3. Rogers HJ, Vardiman JW, Anastasi J, et al. Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study. Haematologica. 2014;99(5):821–9. doi: 10.3324/haematol.2013.096420.
  4. Mrozek K. Cytogenetic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex karyotype. Semin Oncol. 2008;358(4):365–77. doi: 10.1053/j.seminoncol.2008.04.007.
  5. Gohring G, Michalova K, Beverloo HB, et al. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood. 2010;116(19):3766–9. doi: 10.1182/blood-2010-04-280313.
  6. Schoch C, Haferlach T, Haase D, et al. Patients with de novo acute myeloid leukemia and complex karyotype aberrations show a pore prognosis despite intensive treatment: a study of 90 patients. Br J Haematol. 2001;112(1):118–26. doi: 10.1046/j.1365-2141.2001.02511.x.
  7. Гиндина Т.Л., Мамаев Н.Н., Бархатов И.М. и др. Сложные повреждения хромосом у больных с рецидивами острых лейкозов после аллогенной трансплантации гемопоэтических стволовых клеток. Терапевтический архив. 2012;8:61–6. [Gindina TL, Mamaev NN, Barkhatov IM, et al. Complex chromosome damages in patients with recurrent acute leukemias after allogeneic hematopoietic stem cell transplantations. Terapevticheskii arkhiv. 2012;8:61–6. (In Russ)]
  8. Schmid C, Schleuning M, Tischer J, et al. Early allo-SCT for AML with a complex aberrant karyotype – results from a prospective pilot study. Bone Marrow Transplant. 2012;47(1):46–53. doi: 10.1038/bmt.2011.15.
  9. Zaccaria A, Rosti G, Testoni N, et al. Chromosome studies in patients with nonlymphoсytic or acute lymphocytic leukemia submitted to bone marrow transplantation – results of European cooperative study. Cancer Genet Cytogenet. 1987;26(1):51–8.
  10. Schmidt-Hieber M, Blau IW, Richter G, et al. Cytogenetic studies in acute leukemia patients relapsing after allogeneic stem cell transplantation. Cancer Genet Cytogenet. 2010;198(2):135–43. doi: 10.1016/j.cancergencyto.2010.01.005.
  11. Chi HS, Cho YU, Park SH, et al. Comparative analysis of cytogenetic evolution patterns during relapse in the hematopoietic stem cell transplantation and chemotherapy settings of patients with acute leukemia. Blood (ASH Annual Meeting Abstracts). 2013;122(21):1320.
  12. Yuasa M, Uchida M, Kaji D, et al. Prognostic significance of the cytogenetic evolution after the hematopoietic stem cell transplantation in adult acute myeloid leukemia. Blood (ASH Annual Meeting Abstracts). 2013;122(21):1391–2.
  13. Гиндина Т.Л., Мамаев Н.Н., Кондакова Е.В. и др. Острые лимфобластные лейкозы с высокогиперплоидными кариотипами. Вестник гематологии. 2007;4:18–23. [Gindina TL, Mamaev NN, Kondakova EV, et al. Acute lymphoblastic leukemias with highly hyperploid karyotypes. Vestnik gematologii. 2007;4:18–23. (In Russ)]
  14. Schaffer LG, McGowan-Jordan J, Schmid M. ISCN. An International System for Human Cytogenetic Nomenclature. Basel: Karger; 2013.
  15. Schmid C, Labopin M, Nagler A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT acute leukemia working party. J Clin Oncol. 2007;25(31):4938–45. doi: 10.1200/jco.2007.11.6053.
  16. Schroeder T, Czibere A, Platzbecker U, et al. Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia. 2013;27(6):1229–35. doi: 10.1038/leu.2013.7.
  17. Porter DL, Alyea EP, Antin JH, et al. NCI First International Workshop on the biology, prevention and treatment of relapse after allogeneic hematopoietic stem cell transplantation: Report from the Committee on treatment of relapse after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2010;16(11):1467–503. doi: 10.1016/j.bbmt.2010.08.001.
  18. Alyea EP, DeAngelo DJ, Moldrem J, et al. NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies. Biol Blood Marrow Transplant. 2010;16(8):1037–69. doi: 10.1016/j.bbmt.2010.05.005.
  19. de Lima M, Giralt S, Thall PF. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome. Cancer. 2010;116(23):5420–31. doi: 10.1002/cncr.25500.
  20. de Lima M, Porter DL, Battiwalla M, et al. Proceedings from the National Cancer Institute’s Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part III. Prevention and treatment of relapse after allogeneic transplantation. Biol Blood Marrow Transplant. 2014;20(1):4–13. doi: 10.1016/j.bbmt.2013.08.012.
  21. Duque-Afonso J, Lubbert M, Cleary ML. Epigenetic modifications mediated by the AML1/ETO and MLL leukemia fusion proteins. In: Lubbert M, Jones PA, eds. Epigenetic Therapy of Cancer. Berlin Heidelberg: Springer-Verlag; 2014. pp. 121–44. doi: 10.1007/978-3-642-38404-2_6.
  22. Buron F, Malvezzi P, Villar E. Profiling sirolimus-induced inflammatory syndrome a prospective tricentric observational study. PloS One. 2013;8(1):e53078. doi: 10.1371/journal.pone.0053078.
  23. Kondo T, Tasaka T, Matsumoto K, et al. Philadelphia chromosome-positive acute lymphoblastic leukemia with extramedullary and meningeal relapse after allogeneic hematopoietic stem cell transplantation that was successfully treated with dasatinib. Springerplus. 2014;3:177. doi: 10.1186/2193-1801-3-177.
  24. Maziarz RT, Slater S. Post-transplant relapse. In: Maziarz RT, Slater S, eds. Blood and Marrow Transplant Handbook. Springer Science+Business Media, LLC; 2011. pp. 271–6. doi: 10.1007/978-1-4419-7506-5_24.