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Abstract: High-dose chemotherapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with multiple myeloma. Outpatient ASCT can be an attractive option given wait times and costs associated with inpatient procedures. We initiated an outpatient transplantation protocol in 2006. Patients were treated at a university hospital outpatient clinic that was open 5 days a week. The present study investigated safety and cost-effectiveness of the outpatient program. Ninety-one patients underwent ASCT between 2006 and 2010. The majority of patients (77%) had Durie-Salmon stage III disease; 38% had 1 or more comorbidities. Seventy-six patients (84%) were hospitalized during the first 100 days, mainly for febrile neutropenia (n = 71). Overall survival at day 100 was 100%. No patient was admitted to an intensive care unit. Risk factors for prolonged hospitalization (longer than 7 days) were disease stage IIB or higher and age >60 years. The cost savings was $19,522 (Canadian dollars) per patient compared with inpatient ASCT, for an annual savings of approximately $740,000. In summary, outpatient ASCT performed in a weekday clinic for patients with multiple myeloma appears to be safe and cost-effective, but is associated with a relatively high hospitalization rate. [Copyright &y& Elsevier]

Benefits of cord blood (CB) transplantation include low rates of relapse and chronic graft-versus-host disease (GVHD). However, CB use has rapidly declined because of the high rates of infections, severe acute GVHD, and transplant-related mortality (TRM) as well as prolonged hospitalization. We therefore initiated a clinical trial with UM171, a potent agonist of hematopoietic stem cell (HSC) self-renewal, to attempt to solve these limitations and permit transplantation of smaller, better HLA-matched CBs. Expansion culture lasted 7 days and patients received a myeloablative conditioning regimen followed by a single CB transplant including both the expanded CD34+ cells and the lymphocyte-containing CD34- fraction. Between 9/16-11/18, 22 adults with mostly high- to very high-risk hematologic malignancies were transplanted. Median transplant co-morbidity index was 2 (0-5). Five patients had already failed an allogeneic transplant, 3 patients had acute leukemia not in remission, and 2 patients had relapsed/refractory aggressive lymphoma. UM171 treatment profoundly changed the cellular composition of the graft, including a 600 and 8000-fold increase in dendritic and mast cell progenitors, respectively. Neutrophil engraftment was prompt with median time to 100 and 500 neutrophils/μL of 9.5 and 18 days, respectively. Patients seemed to derive clinical benefit from achieving 100 neutrophils rapidly translating into early resolution of febrile neutropenia (median day 7) contributing to shorter hospitalization when compared to conventional CB transplants at same institution with larger cell doses and similar time to 500 neutrophil engraftment. Median CD4 counts at 3 and 12 months were 218 and 413/μL, respectively. Incidence of grade 3-4 acute GVHD was low (9%) and there was no steroid refractory GVHD or moderate-severe chronic GVHD. More than 90% of patients were off immunosuppressive therapy by 12 months. One patient died of TRM (<5%) because of alveolar hemorrhage and 5 patients had relapsed/progressive disease (24%). With a median follow-up of 24 months, 2 year overall, progression-free, and GVHD-and-relapse-free survival were excellent for such a high-risk group at 69%, 72% and 62%, respectively. A 7-day UM171 expansion CB protocol is feasible and provides clinical benefits beyond engraftment, such as very low TRM. If confirmed, UM171 expansion may overcome the shortcomings of CB transplants while maintaining its benefits of low risk of chronic GVHD and relapse. We have now embarked on a phase 2 trial to confirm if a UM171 modified graft, enriched in dendritic cells, will have a potent antileukemia effect in extremely high-risk patients such as refractory leukemias and high risk mutations (e.g.: p53, EVI-1). [ABSTRACT FROM AUTHOR]

We report a patient with PML/RARα-positive acute promyelocytic leukemia (APL) who developed PML/RARα-negative acute myeloid leukemia 37 months after allogeneic bone marrow (BMT) transplant for molecular relapse. Features of myelodysplasia were noted 11 months earlier, chimerism testing by analysis of short tandem repeats was consistent with development of myelodysplasia and acute leukemia within cells of donor origin. To our knowledge, this is the first report of donor cell leukemia following BMT for APL. We hypothesize that replicative stress may lead to the development of some cases of donor cell acute leukemia. [Copyright &y& Elsevier]

Transplantation-associated thrombotic microangiopathy (TA-TMA) has been associated with significantly reduced survival following allogeneic bone marrow transplantation. In this study we describe the course and response to plasma exchange therapy of TA-TMA as well as risk factors for its'' development. Twenty-five patients who underwent plasma exchange therapy were matched to fifty control patients selected for transplant indication and stage of disease at the time of transplant. Transplant indications were acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, aplastic anemia, myelodysplastic syndrome and multiple myeloma. Groups were well balanced with respect to disease status, age at time of transplant and use of radiation-based conditioning. TA-TMA was diagnosed a median of 27 days after transplantation and neurological abnormalities were present in ten cases. Patients received a median of 10 (range 2–43) plasma exchange treatments. Hematological responses were recorded in eight cases. Risk factors for the development of TA-TMA included transplantation from unrelated donors (p=0.002), hepatic venoocclusive disease (VOD) (p=0.034), grade 2-4 acute graft-versus-host disease (GVHD) (p=0.042) and bacteremia with diphtheroid organisms (p=0.009). Only hepatic VOD (p=0.0026) and grade 2-4 acute GVHD (p=0.0436) remained significant risk factors for later development of TA-TMA in a multivariate logistic regression model. The median survival of patients with TA-TMA was 66 (range 32–733) days while that of unaffected patients was 742 (range 15–2392) days after transplantation. Only one patient with TA-TMA remains alive 733 days after transplantation. [Copyright &y& Elsevier]