ABSTRACT
Myelodysplastic syndrome (MDS) is a heterogeneous group of hematological malignancies with considerably variable prognoses and curable only with hematopoietic cell transplantation (HCT). Few studies comparing MDS HCT outcomes between sibling and umbilical cord blood (UCB) donors exist. Using the University of Minnesota Blood and Marrow Transplant (BMT) database, we retrospectively analyzed HCT outcomes among 89 MDS patients undergoing either sibling or double UCB HCT in 2000-2013. We observed similar survival, relapse and non-relapse mortality between sibling and UCB donor sources. Relapse was increased in those with monosomal karyotype (P=0.04) and with reduced intensity conditioning (P<0.01). In summary, our data highlight similar MDS HCT outcomes regardless of donor source and support the use of UCB as an alternative donor when a sibling is unavailable.
Subject(s)
Cord Blood Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/methods , Myelodysplastic Syndromes/pathology , Myelodysplastic Syndromes/therapy , Tissue Donors , Adult , Aged , Cord Blood Stem Cell Transplantation/standards , Databases, Factual , Hematopoietic Stem Cell Transplantation/standards , Humans , Karyotype , Middle Aged , Myelodysplastic Syndromes/diagnosis , Prognosis , Recurrence , Retrospective Studies , Siblings , Transplantation Conditioning/methods , Treatment Outcome , Young AdultABSTRACT
Among patients with myelodysplastic syndrome (MDS) undergoing hematopoietic cell transplantation (HCT), the impact of residual pretransplant cytogenetically abnormal cells on outcomes remains uncertain. We analyzed HCT outcomes by time of transplant disease variables, including (1) blast percentage, (2) percentage of cytogenetically abnormal cells and (3) Revised International Prognostic Scoring System (R-IPSS) cytogenetic classification. We included 82 MDS patients (median age 51 years (range 18-71)) transplanted between 1995 and 2013 with abnormal diagnostic cytogenetics. Patients with higher percentages of cytogenetically abnormal cells experienced inferior 5-year survival (37-76% abnormal cells: relative risk (RR) 2.9; 95% confidence interval (CI) 1.2-7.2; P=0.02; and 77-100% abnormal cells: RR 5.6; 95% CI 1.9-19.6; P<0.01). Patients with >10% blasts also had inferior 5-year survival (RR 2.9; 95% CI 1.1-7.2; P=0.02) versus patients with ⩽2% blasts. Even among patients with ⩽2% blasts, patients with 77-100% cytogenetically abnormal cells had poor survival (RR 4.4; 95% CI 1.1-18.3; P=0.04). Increased non-relapse mortality (NRM) was observed with both increasing blast percentages (P<0.01) and cytogenetically abnormal cells at transplant (P=0.01) in multivariate analysis. We observed no impact of disease burden characteristics on relapse outcomes due to high 1-year NRM. In conclusion, both blast percentage and percentage of cytogenetically abnormal cells reflect MDS disease burden and predict post-HCT outcomes.
Subject(s)
Cost of Illness , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Adolescent , Adult , Aged , Allografts , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/pathology , Myelodysplastic Syndromes/therapy , Survival RateSubject(s)
Boronic Acids/therapeutic use , Hydroxamic Acids/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Pyrazines/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Boronic Acids/administration & dosage , Boronic Acids/adverse effects , Bortezomib , Histone Deacetylase Inhibitors/administration & dosage , Histone Deacetylase Inhibitors/adverse effects , Histone Deacetylase Inhibitors/therapeutic use , Humans , Hydroxamic Acids/administration & dosage , Hydroxamic Acids/adverse effects , Leukemia, Myeloid, Acute/mortality , Myelodysplastic Syndromes/mortality , Pyrazines/administration & dosage , Pyrazines/adverse effects , Treatment Outcome , VorinostatABSTRACT
Umbilical cord blood (UCB) has increased access to hematopoietic cell transplantation (HCT) for patients without HLA-matched sibling donors (MSD). We compared outcomes of HCT using MSD (N=38) or UCB (N=60) among older patients (age ≥ 55 years) with AML or myelodysplastic syndromes (MDS). All patients received a reduced intensity regimen consisting of CY, fludarabine and 200 cGy TBI. Median age at HCT was 63 years for MSD and 61 years for UCB recipients. Among UCB recipients, 95% received two UCB units and 88% received 1-2 locus HLA-mismatched units to optimize cell dose. OS at 3-years was 37% for MSD and 31% for UCB recipients (P=0.21). On multivariate analysis, donor source (MSD vs UCB) did not impact risks of OS, leukemia-free survival and relapse or treatment-related mortality. UCB is feasible as an alternative donor source for reduced-intensity conditioning HCT among older patients with AML and MDS who do not have a suitable MSD.
Subject(s)
Cord Blood Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Transplantation Conditioning/methods , Aged , Female , Histocompatibility Testing , Humans , Male , Middle Aged , Retrospective Studies , Siblings , Tissue Donors , Transplantation, HomologousABSTRACT
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for progression, suggest that myelodysplastic syndromes encompass a multitude of disorders, likely involving numerous pathologic pathways. In fact, it is the effort to understand the underlying biology of these syndromes that has led to recent advances in treatment approaches, including the FDA approval of three new agents (5-azacitidine, decitabine, and lenalidomide) for the treatment of MDS. This review will present data supporting each of the current pathophysiologic pathways implicated in the development and progression of MDS; summarize the emerging clinical paradigms for treating patients with MDS; and offer insights into several novel approaches attempting to improve treatment options for future MDS patients.