Impact of Pretransplant Neutropenia on Post-Transplant Outcome in Patients with Myelodysplastic Syndrome (MDS).

MDS comprises a spectrum of clonal hematopoietic disorders with very heterogeneous clinical courses. Several classification and scoring systems have been developed in an attempt to define subgroups of patients with similar prognoses. The International Prognostic Scoring System (IPSS) incorporates marrow myeloblast count, karyotype, and peripheral blood cytopenias. The recent addition of transfusion requirements to the IPSS (WPSS) has sharpened this prognostic tool. Isolated neutropenia is not reflected in these classifications, but bacterial and fungal colonization and infection are problems in patients with MDS. Hematopoietic cell transplantation is the only treatment strategy that has been shown to have curative potential, and many patients come to transplantation with neutropenia, particularly when the disease progresses. We wanted to determine the impact of neutropenia before transplantation on transplant success. We reviewed results in 291 patients with MDS (including MDS that had transformed to AML [tAML]), 1 to 66 (median 50) years of age, who from 1994 through 2003 were transplanted from related or unrelated donors following conditioning with myeloablative regimens. There were 178 patients (61%) who had neutropenia, defined as <1,500/microliter; in 16 of these (9%) neutropenia was an isolated finding. Among the 178 patients, 137 (47%) had neutrophil counts below 1,000, and 86 (30%) below 500. Patients with neutropenia following recent chemotherapy were excluded. The risk of clinically relevant bacterial infections after transplantation was significantly increased in patients with neutropenia (p=0.001). Neutropenic patients had an increased risk for infections with gram-positive (relative risk [RR] 1.77, p=0.02), but not gram negative bacteria (RR 1.33, p=0.53). Specific organisms for which the RR was significantly increased included coagulase negative Staphylococcus, Bacillus species and Corynebacterium spp., suggesting that at least part of this risk was associated with intravascular catheters. The RR for invasive fungal infections (Candida and Aspergillus spp.) was 2.56 (p=0.03) for patients with <1,500 neutrophils. The hazard rate (HR) for non-relapse mortality by day 100 (21%) was 1.8 (p=0.03), and by 5 years (42%) was 1.62 (p=0.01). The most frequent causes of death were infections. The HR for 5-year mortality was 1.55 (p=0.007) for neutropenic patients. The pattern for the small group of patients with isolated neutropenia was identical to that for all patients with neutropenia. Pre-transplant neutropenia had no significant impact on engraftment or graft-versus-host disease. The probability of survival did not differ significantly between patients with IPSS scores of 0 and 0.5 with isolated or multiple cytopenias. In summary, only few patients with MDS who undergo transplantation have isolated neutropenia. However, pre-transplant neutropenia in patients with MDS is associated with a significantly increased risk of posttransplant bacterial infections, fungal infections, and non-relapse mortality, and a decreased probability of survival after myeloablative transplantation. A correlation with pre-transplantation colonization remains to be determined. Intensified and possibly extended antibiotic coverage should be considered.