Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation

Abstract

ABSTRACTnetic risk classification entered the revised IPSS (IPSS-R) scoring system for patients with MDS, which was renewed in 2012 accordingly. 18 The impact of the revised IPSS-R for MDS patients undergoing SCT was analyzed in one single center study, 13 and more recently in a national multicenter study.14 These studies have shown that the novel classification has greater discriminating power for OS and relapse after SCT than the old IPSS classification. In contrast to the latter studies, we focused only on cytogenetic information of the novel 5-group IPSS-R classification to evaluate the outcome of MDS and sAML patients after SCT in an analysis based on a large cohort from the European Society for Blood and Marrow Transplantation (EBMT) database. The analysis was performed using the latest available karyotype before transplantation, restricted to measurements within one year before SCT.In addition to previous findings 13,14 which also focus on IPSS-R cytogenetics and SCT, we show that poor and very poor risk cytogenetics, within the IPSS-R-cytogenetic risk categories, are strong predictors of poor outcome after transplantation, also when other risk factors are considered simultaneously. Furthermore, the presence of a monosomal karyotype (MK) has an additional impact on RFS and OS, but only in the poor risk group and not in the very poor risk cytogenetics group of patients. MethodsPatients with MDS or sAML with available cytogenetic information within 12 months before transplantation and an HLAmatched donor were identified from the EBMT-database. Cytogenetic information, as reported to the database, was reviewed and classified according to MK, IPSS 16 and IPSS-R. 18Patients who received more than one allograft were kept in the analysis and the outcome of the first SCT was used. Base-line information, transplant-characteristics and follow-up information of patients were down-loaded from the database. Definition of disease status at SCTDisease status at SCT was defined according to the FAB 19 or WHO classification, 20 to remission status and to prior chemotherapy. These definitions led to 4 patient groups: 1) patients with refractory anemia (RA), RA with ringsideroblasts (RARS) or refractory cytopenias with multilineage dysplasia (RCMD) who had never had higher MDS-stages (RA with excess of blasts, RAEB; chronic myelomonocytic leukemia, CMML, sAML) and who did not receive chemotherapy before SCT; 2) RAEB or RAEB in transformation (RAEB(t))/sAML/CMML without induction chemotherapy and, therefore, not in remission; 3) RAEB or RAEB(t)/sAML/CMML with induction chemotherapy leading to complete remission (CR); 4) RAEB or RAEB(t)/sAML/CMML with refractory disease or relapse after induction chemotherapy.We did not include percentage of bone marrow blasts in our analysis since our definition of patient groups contains this information. Patients who received hypomethylating agents were considered as patients without chemotherapy, since statistical comparison showed that there was no difference between outcomes of RAEB(t)/...

CD34-Selected Hematopoietic Stem Cell Transplants Conditioned with Myeloablative Regimens and Antithymocyte Globulin for Advanced Myelodysplastic Syndrome: Limited Graft-versus-Host Disease without Increased Relapse

“…Similarly, a CIBMTR study showed relapse rates in the order of 25-28% and higher in patients with poor risk cytogenetic abnormalities or patient who underwent NMA conditioning regimen 43 . Relapse strongly correlated in our series with cytogenetic risk at diagnosis, similarly to what has been published for patients undergoing unmodified transplant in a large retrospective study reported by EBMT 44 . Patients with poor risk cytogenetic abnormalities had a relapse rate of 31% at 1 year compared to only 17% in patients with intermediate risk and 8% in patients with low risk.…”

Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies

“…The revised IPSS confirmed poor prognosis for the very poor cytogenetics category (40). MK+MDS after allogeneic HCT has been described with similar poor outcomes (41–44). The current analysis also demonstrated that MK+MDS were associated with higher TRM, in contrast to the models in AML in which the cytogenetic group had no impact on TRM.…”

Impact of primary disease on outcome after allogeneic stem cell transplantation for transformed secondary acute leukaemia

“…Smaller single centre studies described dismal outcome of transformed MPN and CMML (Mesa et al , ). Reports about allo‐HSCT in transformed leukaemia are mainly published regarding the preceding haematological disease such as MDS (Koenecke et al , ), MPN (Lussana et al , ), CMML (Symeonidis et al , ) or aplastic anaemia (Hussein et al , ). Larger systematic reports are lacking.…”