Phase I trial of parathyroid hormone to facilitate stem cell mobilization.

Autologous stem cell transplantation is a curative procedure for many patients with lymphomas, and has been shown to improve survival in patients with multiple myeloma. Approximately 20% of patients are unable to mobilize sufficient hematopoietic stem cells to proceed safely to autologous stem cell transplantation. Parathyroid hormone (PTH) affects osteoblasts and the stem cell niche, and has been shown to improve survival when given posttransplant in a mouse competitive transplant model. In this Phase I study, 20 subjects who had 1 or 2 unsuccessful stem cell mobilization attempts, received PTH in escalating doses of 40 microg, 60 microg, 80 microg, and 100 microg for 14 days. On days 10-14 of treatment, subjects received filgrastim 10 microg/kg. The PTH was tolerated well and there was no dose-limiting toxicity. Forty-seven percent of subjects who had failed 1 prior mobilization attempt met the mobilization criteria of >5 CD 34(+) cells/microL in the peripheral blood. Forty percent of subjects who failed to reach adequate CD34(+) cell counts in 2 prior mobilization attempts met the mobilization criteria. PTH was well tolerated at doses up to 100 microg in human cancer patients. The efficacy of PTH for mobilization of hematopoietic stem cells will need to be tested in a larger Phase II study.