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Donor Leukocyte Infusions Are Effective in Relapsed Multiple Myeloma After Allogeneic Bone Marrow Transplantation
H.M. Lokhorst,
A. Schattenberg,
J.J. Cornelissen,
L.L.M. Thomas, and
L.F. Verdonck
From the Department of Haematology, University Hospital Utrecht, Utrecht, The Netherlands; the Department of Haematology, University Hospital, Nijmegen, The Netherlands; the Department of Haematology, Dr. Daniel den Hoed Clinic, Rotterdam, The Netherlands; and the Department of Haematology, Academic Medical Center, Amsterdam, The Netherlands.
Donor leukocyte infusions (DLI) can induce sustained remissions in patients with acute and chronic myeloid leukemia who relapse after allogeneic bone marrow transplantation (allo-BMT). Also, in multiple myeloma (MM), incidental reports have indicated the existence of a graft-versus-myeloma effect (GVM) induced by allo-reactive T cells. We performed a retrospective study in a larger group of MM patients to characterize better the effect, prognostic factors, and toxicity of this new treatment modality. Thirteen patients with relapsed MM after allo-BMT were studied. Patients received a total of 29 DLI with T-cell doses ranging from 1 × 106/kg to 33 × 107/kg. Repetitive courses, sometimes with escalated cell doses, were undertaken in case of no response to or relapse after DLI. Eight of 13 patients responded: 4 patients achieved a partial remission and 4 patients achieved a complete remission. Dose escalation was effective in 3 patients. The time to response was median 6 weeks (range, 4 to 10 weeks). Major toxicities were secondary to acute and chronic graft-versus-host disease (GVHD), which occurred in 66% and 56% of all patients and in 87% and 85% of the responders, respectively. Two responding patients developed fatal BM aplasia. The only prognostic factors for response were a T-cell dose greater than 1 × 108/kg and the occurrence of GVHD. Seven of nine patients developing acute GVHD responded, as compared with only 1 response in the 4 patients without GVHD and 6 of 7 patients with chronic GVHD responded, whereas no response was observed in the 5 patients without chronic GVHD. DLI are effective in a high percentage of patients with relapsed MM after allo-BMT, although it is associated with a high treatment-related toxicity. The dose of T cells used may be important in determining the GVM effect, with the highest probability of response after infusion of more than 1 × 108 T cells. Because the optimal individual dose may vary, patient-adapted therapy consisting of repeated infusions with escalating dose of donor leukocytes until maximum response is achieved may therefore be preferable.
Blood, Vol. 90 No. 10 (November 15), 1997:
pp. 4206-4211
© 1997 by The American Society of Hematology.

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|

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|
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|

|
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|
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|

|
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J. Clin. Oncol.,
January 1, 1999;
17(1):
208 - 208.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
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E. P. Alyea, R. J. Soiffer, C. Canning, D. Neuberg, R. Schlossman, C. Pickett, H. Collins, Y. Wang, K. C. Anderson, and J. Ritz
Toxicity and Efficacy of Defined Doses of CD4+ Donor Lymphocytes for Treatment of Relapse After Allogeneic Bone Marrow Transplant
Blood,
May 15, 1998;
91(10):
3671 - 3680.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|