Treatmentrelated Toxicity And GvHd Following Myeloablative Allogeneic Transplantation

While allogeneic transplantation following myeloabla-tive therapy is associated with potent antitumor activity in patients with myeloma, most clinical trials have reported significant TRM, limiting the effectiveness of this approach. Acute and chronic GvHD contribute to the high TRM. The incidence of grade II-IV acute GvHD in patients receiving cyclosporine and methotrexate ranges as high as 78% in some studies, with an incidence of grade III-IV GvHD of 14-19%. In the EBMTR registry, patients with grades III and IV GvHD had an extremely poor survival.14'23

Using selective T-cell depletion with anti-CD6 monoclonal antibody and complement lysis, investigators at DFCI have reduced the incidence of significant GvHD after transplant in patients with multiple myeloma. When T-cell depletion is used as the only means of GvHD prophylaxis, the incidence of severe grade III or IV acute GvHD is less than 7%, with no deaths attributable to GvHD.21 No evidence of GvHD was identified in 47% of patients, while 36% and 12% patients had grades I and II GvHD, respectively. Chronic GvHD was noted in only 20% of patients. Using an in vivo T-cell depletion approach, Kroger et al. reported a similar low incidence of severe GvHD and an overall 6-year progression-free survival of 31%.27 Unfortunately, this reduction in toxicity related to GvHD has not been associated with an increased overall survival rate. As an example, a recent study using a partial T-cell depletion approach after myeloablative transplantation was associated with a low complete response rate (6%) after trans-planation.28 The EBMTR has reported that patients receiving T-cell depletion had a similar survival in comparison to patients receiving other methods of GvHD prophylaxis.14,23

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