Ex Vivo Umbilical Cord Blood Expansion Hastens Stem Cell Engraftment in Transplant Recipients
Engraftment of stem cells from umbilical cord blood can be hastened with pretransplantation expansion of the stem cells on a bed of mesenchymal precursor cells, according to a recent study.
The phase I/II trial analyzed engraftment results for 31 patients with hematologic cancers who had each received one expanded cord blood unit and one unmanipulated cord blood unit. These patients’ results were compared with the records of 80 patients who had received only the standard two units of unmanipulated cord blood.
In the units of expanded cord blood, the total number of nucleated cells increased by a median factor of 12, and CD34-positive cells, which are crucial for engraftment, increased by a median factor of 30. Among patients who received expanded cord blood, the cumulative incidence of neutrophil engraftment was 88% at 26 days and the cumulative incidence of platelet engraftment was 71% at 60 days; for the historical controls, those incidences were 53% and 31%, respectively.
Until now, the benefits of cord blood cell transplants have been counterbalanced by slow engraftment, which increases the risk of transplant-related complications. This slowness is attributable to the low number of hematopoietic stem cells per unit of umbilical cord blood. With ex vivo expansion, researchers were able to greatly increase the number of cord blood cells transplanted, reduce neutrophil and platelet recovery times, and increase the percentage of patients for whom successful engraftment took place.
The study’s report was published in the December 13 edition of the New England Journal of Medicine. Senior author Elizabeth Shpall, M.D., a professor in the Department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center, said, “Pretransplant cord blood expansion on mesenchymal stromal cells could become the new standard of care if our findings are confirmed in a randomized clinical trial.”
Ibrutinib Shows Promise for Mantle Cell Lymphoma Treatment
An international phase II study of the experimental drug ibrutinib for the treatment of relapsed or refractory mantle cell lymphoma is showing durable responses with few side effects.
Mantle cell lymphoma is a rare subtype of B-cell lymphoma. Ibrutinib inhibits Bruton tyrosine kinase, which transduces signals from the B-cell receptor, a protein on the cell surface that enables B cells to bind to antigens. B-cell receptor signaling also plays an important role in the normal development of B cells. By inhibiting Bruton tyrosine kinase, ibrutinib causes cell death and decreases migration and adhesion of malignant B cells.
Rates of serious adverse events were low among the 111 patients in the interim safety analysis. Grade 3 or higher adverse events consisted of neutropenia in 11% of patients and anemia, diarrhea, dyspnea, pneumonia, and thrombocytopenia each in 5% of patients. These were similar to the safety data from earlier studies.
Of the 109 patients evaluable for efficacy, 47% had a partial response and 19% had a complete response. The median time this group of patients had been receiving ibrutinib was 6 months. Among the patients who had been receiving ibrutinib longest (median, 11 months), the complete response rate was 35%.
“What impressed me the most is the high complete response rate, which continues to improve with time,” said Michael Wang, M.D., an associate professor in the Department of Lymphoma and Myeloma and the director of the Mantle Cell Lymphoma Program at The University of Texas MD Anderson Cancer Center. “Ibrutinib is the safest drug we have for mantle cell lymphoma. Previously, such a rate could be achieved only with combination cytoreductive chemotherapy, which suppresses bone marrow and is toxic.”
Dr. Wang and his colleagues presented their interim results at the 54th American Society of Hematology Annual Meeting and Exposition in December. “I believe we are witnessing a breakthrough in mantle cell lymphoma,” Dr. Wang said. “This is great news for patients.”
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Other articles in OncoLog, February 2013 issue: