Transplantation of ex vivo expanded cord blood.

Umbilical cord blood (CB) from unrelated donors is increasingly used to restore hematopoiesis after myeloablative therapy. CB transplants are associated with higher rates of delayed and failed engraftment than are bone marrow transplants, particularly for adult patients. We studied the ex vivo expansion of CB in an attempt to improve time to engraftment and reduce the graft failure rate in the recipients. In this feasibility study, 37 patients (25 adults, 12 children) with hematologic malignancies (n = 34) or breast cancer (n = 3) received high-dose therapy followed by unrelated allogeneic CB transplantation. A fraction of each patient's CB allograft was CD34-selected and cultured ex vivo for 10 days prior to transplantation in defined media with stem cell factor, granulocyte colony-stimulating factor, and megakaryocyte growth and differentiation factor. The remainder of the CB graft was infused without further manipulation. Two sequential cohorts of patients were accrued to the study. The first cohort had 40% and the second cohort had 60% of their CB graft expanded. Patients received a median of 0.99 x 10(7) total nucleated cells (expanded plus unexpanded) per kilogram. The median time to engraftment of neutrophils was 28 days (range, 15-49 days) and of platelets was 106 days (range, 38-345 days). All evaluable patients who were followed for 28 days or longer achieved engraftment of neutrophils. Grade III/IV acute GVHD was documented in 40% and extensive chronic GVHD in 63% of patients. At a median follow-up of 30 months, 13 (35%) of 37 of patients survived. This study demonstrates that the CD34 selection and ex vivo expansion of CB prior to transplantation of CB is feasible. Additional accrual will be required to assess the clinical efficacy of expanded CB progenitors.

Renal dysfunction in allogeneic hematopoietic cell transplantation.

BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT), formerly called bone marrow transplantation, can potentially cure various malignant and non-malignant diseases, but it is associated with a high risk of toxicity. We have previously shown an overall 21% incidence of severe acute renal failure in patients undergoing autologous HCT. The present study evaluated renal dysfunction in patients undergoing allogeneic HCT. METHODS: The clinical course of 88 adult patients who received allogeneic HCT at the University of Colorado Health Science Center was analyzed. Renal dysfunction was classified as follows: Grade 0 = normal renal function; Grade 1 =>25% decrement in GFR but twofold increase in serum creatinine; Grade 3 =>twofold increase in serum creatinine and need for dialysis. RESULTS: Of the 88 patients, 81 (92%) patients had some degree of renal dysfunction (Grade 1, 20 patients; Grade 2, 32 patients; Grade 3, 29 patients). Severe nephrotoxicity (Grade 2 and Grade 3 renal dysfunction) was associated with significantly higher frequencies of sepsis, hepatic toxicity and hepatic veno-occlusive disease (VOD), and lung toxicity. The overall mortality rate at the end of 6 months was 58%. Grade 3 renal dysfunction was associated with a significantly increased risk of mortality (82.6%). CONCLUSION: A 92% incidence of renal dysfunction in allogeneic HCT patients was found. Lung and liver toxicities were significantly correlated with developing renal dysfunction, and the mortality rates for patients with Grade 3 renal failure exceeded 80%.