Cytogenetic Abnormalities in Primary Myelodysplastic Syndrome Are Highly Predictive of Outcome After Allogeneic Bone Marrow Transplantation

Abstract

Allogeneic bone marrow transplantation (BMT) is the only curative therapy available for patients with myelodysplastic syndrome (MDS). In an attempt to identify prognostic factors influencing outcome, we collected data retrospectively on 60 consecutive adult patients who had undergone BMT at our center for primary MDS or acute myelogenous leukemia evolving from preexisting primary MDS (sAML). Patients were divided into subgroups according to cytogenetic abnormalities based on a recently described International MDS Workshop categorization system. The 7-year actuarial event-free survival (EFS), relapse rate, and nonrelapse mortality (NRM) for all patients were 29% (95% confidence interval [CI], 16% to 43%), 42% (CI, 24% to 67%), and 50% (CI, 37% to 64%), respectively. The EFS for the good-, intermediate-, and poor-risk cytogenetic subgroups were 51% (CI, 30% to 69%), 40% (CI, 16% to 63%), and 6% (CI, 0% to 24%), respectively (P= .003). The corresponding actuarial relapse rates were 19% (CI, 6% to 49%), 12% (CI, 2% to 61%), and 82% (CI, 48% to 99%), respectively (P = .002) with no difference in NRM between the subgroups. Univariate analysis showed cytogenetic category, French-American-British (FAB) subtype, and graft-versus-host disease (GVHD) prophylaxis used to be predictive of relapse and EFS. In multivariate analysis, only the cytogenetic category was predictive of EFS, with the relative risk of treatment failure for the good-, intermediate-, and poor-risk cytogenetic subgroups being 1.0, 1.5, and 3.5, respectively (P = .004). For adults with primary MDS and sAML, even after BMT, poor-risk cytogenetics are predictive of an unfavorable outcome; novel treatment strategies will be required to improve results with allogeneic BMT in this patient population. © 1998 by The American Society of Hematology.

Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia

“…Unfortunately, many studies show that the presence of poor-risk karyotypes adversely affects outcome after alloSCT. 6,[12][13][14][15][16][17][18][19][20][21][22] However, the number of patients with poor karyotypic risk in these studies is very low, which prevents to draw firm conclusions. Only one prospective trial addressed the question whether outcome of poor-risk MDS patients treated with intensive chemotherapy followed by alloSCT was superior to consolidation with autologous SCT in a donor versus no donor comparison.…”

Hematopoietic Cell Transplantation for Adult Patients With Myelodysplastic Syndromes and Myeloproliferative Disorders

“…6,7, These studies had between 12 and 1378 patients with median ages ranging from 19.0 to 58.8 years. The conditioning regimens differed widely depending on the active protocols at the time of transplantation at the respective centers (the regimen used for most patients at the respective centers is listed): cyclophosphamide-total body irradiation (TBI), 6,9,22 busulfan-TBI, 44 cyclophosphamide-TBI with liver and lung shielding, 38 busulfan-cyclophosphamide, 20,23,25,30,35,36,42 busulfan-cyclophosphamide-cytosine arabinoside, 21 cyclophosphamide-TBI-busulfan, 24 cyclophosphamide-TBIcytosine arabinoside, 18 cyclophosphamide-TBI-cytosine arabinoside or etoposide, 27 busulfan-cyclophosphamidethiotepa, 39 TBI-cytosine arabinoside, 33 cyclophosphamide-TBI-idarubicin, 29 TBI-based regimens, 7,17,31,32 or various regimens. 26,28,34,41,43 In these studies, depending on the individual risk profile, relapse-free survival at 2 to 7 years ranged from 8% to 74%.…”

“…Various prognostic parameters to predict relapse, survival, and nonrelapse mortality were analyzed by different statistical models; percentage of marrow blasts (disease stage/FAB subgroup) at the time of transplantation was consistently shown to be predictive of relapse. 7,17,19,22,24,[26][27][28][30][31][32]35,37,[40][41][42]44 Cytogenetic IPSS category 6,30,35,42,44 and the total IPSS score 6,7,35,42 were also strong predictors of relapse ( Figure 1). Younger age 19,20,22,25,28,31,32,36,37 and shorter disease duration 22,25,31,32,41,44 correlated with improved overall survival and relapse-free survival primarily because of a lower nonrelapse mortality.…”

“…6,7, Advanced MDS.-The risk of posttransplantation relapse increases with the proportion of marrow blasts present at the time of transplantation (advanced MDS [RAEB/RAEB-T]). 17,19,22,26,28,[30][31][32]42 Relapse rates in the range of 14% to 71% have been reported in patients with RAEB, RAEB-T, or secondary AML. 19,22,24,26,[30][31][32]35,42 More intensive conditioning regimens including busulfan-cyclophosphamide-TBI, 24 cyclophosphamide-TBI-cytosine arabinoside or etoposide, 27 cyclophosphamide-TBI-idarubicin, 29 or busulfan-cyclophosphamide-thiotepa 39 showed high nonrelapse mortality (68%, 24 50%, 27 42% 39 ) with similar relapse-free survival and relapse rates compared with busulfan-cyclophosphamide or cyclophosphamide-TBI regimens.…”

Myelodysplastic Syndromes Clinical Practice Guidelines in Oncology

“…Allogeneic HSCT from an HLA-matched sibling donor is a preferred approach for treating a portion of patients with MDS, particularly those with high-risk disease. [88][89][90][91][92][93][94][95][96] Matched nonmyeloablative transplant regimens 97,98 and matched unrelated donor stem cell transplants [99][100][101] are becoming options at some centers to treat these patients. In certain investigative settings, autologous bone marrow or peripheral blood stem cell transplantation is being considered.…”