We explored for graft-vs-tumor (GVT) effects following nonmyeloablative allogeneic blood stem cell transplantation in metastatic melanoma, a tumor susceptible to immunebased therapy. Eligible patients (pts) were less than 60 yrs of age, had progressive metastatic disease despite prior therapy, and had a HLA identical family donor. Nonmyeloabiative conditioning consisted of fludarabine 25 mg/m2 for 5 days and cyclophosphamide 60 mg/ kg x×2 days. A G-CSF mobilized PBSC transplant was infused on day 0. Cyclosporine (CSA) was given as GVHD prophylaxis and was withdrawn early in pts with mixed T-cell chimerism or disease progression, to promote a GVT effect. Pts with persistent mixed Tcell chimerism or disease progression following CSA withdrawal were eligible for donorlymphoctye infusions (DLI). A total of 15 pts were transplanted at our 2 institutions from 11/97 to 6/00. Donor engraftment was confirmed in 13/13 évaluable pts by PCR of minisatellite regions, although 2 subsequently had graft rejection with autologous hematopoietic recovery. One of 15 pts survives; 2 (13%) died of transplant-related complications (GVHD and idiopathic encephalitis) and 12 (80%) from disease progression. Median survival was 86 days (range 7-287). In 3, rapid melanoma progression resulted in death within one month of transplantation. Six of 11 évaluable pts developed grade II-IV acute-GVHD; 5 responded to treatment while one died from liver GVHD. Limited chronic GVHD occurred in 3. Three pts received 1 to 3 DLI following CSA withdrawal without evidence for a GVT effect. Four pts (27%) had a partial tumor response. Regression of metastatic disease occurred in proximity to transplant conditioning and was not associated with CSA withdrawal, DLI or acute or chronic-GVHD. Furthermore, disease regression was not durable, with tumor progression and death occurring in all responders within 1 to 7 months. We conclude that transient regression of metastatic melanoma may occur following NST. The proximity of tumor regression to transplant conditioning and the short-lived nature of these responses suggest they occurred as a result of cytotoxic chemotherapy rather than from a GVT effect. The high-risk of early death from rapid tumor progression limits future investigation for GVT effects in metastatic melanoma to those with less advanced or slowly progressive disease.
|Number of pages||1|
|Issue number||11 PART II|
|Publication status||Published - 2000|