Non-myeloablative conditioning and allogeneic transplantation for multiple myeloma.
In multiple myeloma (MM), allogeneic stem cell transplantation (alloHCT) carries a lower relapse risk than autologous transplantation but a greater transplant-related mortality. Nonmyeloablative conditioning for allogeneic transplantation (NST) reduces transplant-related toxicity. Results are encouraging when used during first remission in low-risk patients, but less-so in relapsed or refractory disease. This is a single-center retrospective analysis of 20 previously treated MM patients who underwent NST from matched-related or matched-unrelated donors from 2000-2006. Median age was 52.7 years (37.2-68.0). Twenty-five percent had advanced or high-risk disease. Eleven still had active disease prior to NST. Conditioning was total body irradiation 200 cGy on a single fraction on day -5, followed by antithymocyte globulin (ATG) 1.5 mg/kg/day and fludarabine 30 mg/m(2)/day on days -4 to -2. All received immunosuppression, most commonly with oral mycofenylate mofetil and cyclosporine beginning on day -5. At day 100, 50% had achieved complete remission. Transplant-related mortality was 25%. Median overall survival (OS) was 21.2 months (0.6-90+) and progression-free survival (PFS) 6.6 months (0.6-90+). Both OS and PFS were 24% at 3 years. OS was significantly greater for patients with age <52 years (median 27 months vs. 7.9 months, P = 0.031), and there was a trend toward greater OS for those with beta2 microglobulin <2.5 mg/l (median 27 months vs. 7.7 months, P = 0.08). Donor characteristics and Ig type had no significant effect on survival. These data suggest a benefit of NST in relapsed/refractory MM. Randomized trials must be performed to confirm and further qualify this benefit.
Osman
Keren
K
The Bone Marrow Transplant Program, The Mount Sinai Medical Center, New York, NY, USA. keren.osman@mountsinai.org
Elliott
Brian
B
Mandeli
John
J
Scigliano
Eileen
E
Malone
Adriana
A
Isola
Luis
L
Grosskreutz
Celia
C
D000328:Adult; D000368:Aged; D000375:Aging; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation; D001613:beta 2-Microglobulin / Q000097:blood
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D001613:beta 2-Microglobulin; D014740:Vidarabine; C024352:fludarabine