Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte antigen mismatch.

Although reduced-intensity conditioning has become standard of care for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT), the optimum regimen has yet to be defined, and may depend on pretransplantation patient- and/or disease-specific risk factors. We report here results in 100 adults, ages 18 to 69, with high-risk hematologic malignancy who received conditioning with fludarabine, carmustine, melphalan, and rabbit antithymocyte globulin (FBM-A). Outcomes were stratified using the disease risk index (DRI) as published by Armand et al. (Blood 2012;120:905-913). Median age was 56, and patients were ineligible for standard myeloablative conditioning because of age, organ dysfunction, or prior autologous HCT. Patients underwent transplantation for myeloid (acute myelogenous leukemia, n = 40; myelodysplastic syndrome, n = 24; myelofibrosis, n = 13; other myeloid, n = 2) or lymphoid (acute lymphoblastic leukemia, n = 8; non-Hodgkin lymphoma, n = 8; Hodgkin lymphoma, n = 4, chronic lymphocytic leukemia, n = 1) malignancy. Donors were related in 26 patients (22 matched, 4 mismatched at 1 antigen) and unrelated in 74 (mismatched at 1 or 2 HLA loci in 33); grafts were peripheral blood stem cells in 97 patients, bone marrow in 2, and double cord in 1. According to the DRI, 68 patients were classified as low (n = 1) or intermediate risk (n = 67), and 32 were classified as high (n = 28) or very high risk (n = 4). With a median follow-up of surviving patients of 18 months, the Kaplan-Meier estimate of overall survival at 2 years for patients in the low/intermediate risk group is 80%, compared with 66% in the high/very high group (P = .11). Two-year cumulative incidence of relapse and nonrelapse mortality in the low/intermediate group are 9.9% and 15%, versus 25% and 19% in the high/very high group (respective P values .07 and .81). The cumulative incidence of acute graft-versus-host (GVHD) grades III to IV at 100 days was 8.1%, and the incidence of National Institutes of Health-defined moderate to severe chronic GVHD was 22% at 2 years. No deaths were attributable to chronic GVHD. Survival was not influenced by age, hematopoietic comorbidity index score, donor type, donor gender, or presence of mismatch. We conclude that FBM-A is an effective and safe conditioning regimen for adults up to age 69 with hematologic malignancies who have low-, intermediate-, or high-risk scores according to the DRI.

Alefacept in corticosteroid refractory graft versus host disease: early results indicate promising activity.

Steroid refractory graft versus host disease (GVHD) presents a significant therapeutic challenge due to the limited efficacy and safety of second-line treatments. Three patients with extensively pretreated, refractory GVHD were treated with a targeted anti-T-cell agent, alefacept, and demonstrated rapid and clinically significant improvement in their GVHD, facilitating tapering of corticosteroids. The pathological and immunohistochemical findings of GVHD also improved, validating our clinical impression. These preliminary findings indicate that alefacept may have beneficial activity in GVHD warranting further study.

Outcome and prognostic factors of hematopoietic stem cell transplantation recipients admitted to a medical ICU.

OBJECTIVE: To assess the outcome of adult hematopoietic stem cell transplantation (HSCT) recipients who were admitted to a medical ICU (MICU), and to identify the measurable predictors of their MICU outcome. DESIGN: Retrospective chart review study. SETTING: MICU in a tertiary care, university-affiliated medical center with a comprehensive cancer program. PATIENTS: Consecutive adult HSCT recipients admitted to the MICU between January 1998 and June 2001. MEASUREMENTS AND MAIN RESULTS: Eighty-five patients were admitted to the MICU, representing 11.4% of patients who had undergone HSCT during the study period. The mean (+/- SD) age at MICU admission was 46.6 +/- 11.4 years (women, 67%; men, 33%). Forty-five patients (53%) underwent allogeneic HSCT, and 40 patients (47%) underwent autologous HSCT. Fifty-one patients (60%) required mechanical ventilation (MV). Fifty-two patients (61%) survived their MICU stay, and 35 patients (41%) were discharged alive from the hospital. The long-term survival rate (ie, > 6 months) in this cohort was 28%. Nineteen mechanically ventilated patients (37%) survived their MICU stay, and 33 patients (97%) survived who did not require MV (p < 0.01). The independent predictors of poor outcome during the MICU stay were elevated serum lactate level on admission to the MICU, the need for MV, and the presence of more than two organ systems that failed. CONCLUSIONS: The study showed short-term and long-term survival rates among adult HSCT recipients who had been admitted to MICU that were higher than those previously reported. While there were no absolute predictors of mortality, patients with higher MICU admission serum lactate levels, those requiring MV, or those developing more than two organ system failures had poor MICU outcomes.

Pulmonary complications following hematopoietic stem cell transplantation: diagnostic approaches.

Pulmonary complications are a significant cause of morbidity and mortality in hematopoietic stem cell transplant recipients. Pulmonary infiltrates in such patients pose a major challenge for clinicians because of the wide differential diagnosis of infectious and noninfectious conditions. It is rare for the diagnosis to be made by chest radiograph, and commonly these patients will need further invasive and noninvasive studies to confirm the etiology of the pulmonary infiltrates. This review describes the role of the different diagnostic tools available to reach a diagnosis in a timely manner in this patient population.