Low Dose Thalidomide and Donor Lymphocyte Infusion as Adoptive Immunotherapy after Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1646-1646
Author(s):  
Nicolaus Kroeger ◽  
Avichai Shimoni ◽  
Maria Zagrivnaja ◽  
Francis Ayuk ◽  
Michael Lioznov ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Adoptive Immunotherapy ◽  
Low Dose ◽  
Progressive Disease ◽  
Donor Lymphocyte Infusion ◽  
Graft Versus Host

Abstract To improve anti-myeloma effect of donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation in multiple myeloma, we investigated in a phase I/II study the effect of low dose thalidomide (100 mg) followed by DLI in 18 patients with progressive disease or residual disease and prior ineffective DLI after allografting. The median age was 53 years (range 31–64). Twelve patients received prior DLI and either relapsed again (n=1), or showed no response (PD: n=3; SD: n=8). The overall response rate was 67% including 22% complete remission. Major toxicity of thalidomide was weakness grade I/II (68%) and peripheral neuropathy grade I/II (28%). Only 2 patients experienced mild grade I acute graft versus host disease (aGvHD) of the skin, while no grade II-IV aGvHD was seen. De novo limited chronic GvHD (cGvHD) was seen in two patients (11%). The median time to response was 108 days (range, 36–266 days). In 5 patients not responding to 100 mg, the dose of thalidomide was increased (200 mg n=4; 300 mg n=1) and subsequently two of them responded with partial remission. In three patients dose escalation of DLI was performed, resulting in one minor and one partial remission. No difference regarding response was observed between unrelated and related donors (66% each). Five out of 6 patients with deletion 13 responded, while 5 out of 9 patients without deletion 13 responded to thalidomide plus DLI. In patients who failed to respond to prior DLI, the disease status could be converted in 6 patients with SD after first DLI into CR (n=2), PR (n=3), MR (n=1) while two with SD remainded SD after thalidomide plus DLI. In three patients with progressive disease after DLI the combination of thalidomide and DLI resulted in one CR, one PR and one minor remission. The two-years estimated overall and progression-free survival was 100 % and 84%, respectively. Adoptive immunotherapy with low dose Thalidomide and DLI induces strong anti-myeloma effect with low incidence of graft versus host disease.

Low-dose thalidomide and donor lymphocyte infusion as adoptive immunotherapy after allogeneic stem cell transplantation in patients with multiple myeloma

Blood ◽  
2004 ◽  
Vol 104 (10) ◽  
pp. 3361-3363 ◽  
Author(s):  
Nicolaus Kröger ◽  
Avichai Shimoni ◽  
Maria Zagrivnaja ◽  
Francis Ayuk ◽  
Michael Lioznov ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Adoptive Immunotherapy ◽  
Low Dose ◽  
Donor Lymphocyte Infusion ◽  
Graft Versus Host

Abstract To improve the antimyeloma effect of donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation in multiple myeloma, we investigated in a phase 1/2 study the effect of low-dose thalidomide (100 mg) followed by DLI in 18 patients with progressive disease or residual disease and prior ineffective DLI after allografting. The overall response rate was 67%, including 22% complete remission. Major toxicity of thalidomide was weakness grade I/II (68%) and peripheral neuropathy grade I/II (28%). Only 2 patients experienced mild grade I acute graft versus host disease (aGvHD) of the skin, while no grades II to IV aGvHD was seen. De novo limited chronic GvHD (cGvHD) was seen in 2 patients (11%). The 2-year estimated overall and progression-free survival were 100% and 84%, respectively. Adoptive immunotherapy with low-dose thalidomide and DLI induces a strong antimyeloma effect with low incidence of graft versus host disease. (Blood. 2004;104:3361-3363)

5-Azacitidine in Combination with Donor Lymphocyte Infusions for the Treatment of Patients with MDS or AML Relapsing after Allogeneic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5341-5341 ◽  
Author(s):  
Akos Czibere ◽  
Thorsten Graef ◽  
Jens Lind ◽  
Norbert Gattermann ◽  
Fabian Zohren ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Progressive Disease ◽  
Myelogenous Leukemia ◽  
Graft Versus Host

Abstract Purpose: Therapeutic options for patients with high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) who relapse after allogeneic stem cell transplantation (SCT) are limited and prognosis is dismal. If applicable, transfusion of donor lymphocytes (DLI) with or without chemotherapy is the current standard therapy. But, in contrast to chronic myelogenous leukemia (CML), response rates after sole DLI in patients with relapsing MDS or AML after allogeneic SCT are poor. Addition of chemotherapy, usually low-dose cytarabine 100mg/m2 as continuous infusion for 7 days, can increase response rates only marginally. Also important, duration of response is short and long term survival even rare. The demethylating agent 5-aza-2′-deoxycytidine (5-Aza) has been shown to be effective in the treatment of MDS and AML. In addition to a direct cytotoxic effect, treatment with this demethylating drug also results in a rapid and stable transcription and cell surface expression of formerly unexpressed killer Ig-like receptors (KIRs) in natural killer cells (NK cells), thereby possibly enhancing the GvL effect of DLI. Patients & treatment: In an intent-to-treat approach we treated 6 patients with high risk MDS or AML who relapsed after allogeneic SCT with 5-Aza plus DLI. Patients’ median age was 47.5 years (range 32–71 years). Before allogeneic SCT 4 patients had active disease, and 2 were in complete remission (CR). Two had family donors, 4 had unrelated donors. Median time for relapse after SCT was day +99 (range day +84 to day +300). Once relapse was diagnosed patients received 100mg/m2 5-Aza for five days via subcutaneous injection in two to four weeks intervals. If practical, patients received 1×106 CD3+ cells/kg bodyweight following the first course of 5-Aza, and in the absence of graft-versus host disease, this was followed by additional 5×106 CD3+ cells/kg bodyweight after 3 months. Results: Five out of 6 patients responded to treatment with 5-Aza and DLI. Three patients achieved a complete remission (CR), two a partial remission (PR) and one patient died early due to progressive disease. Two patients developed extensive graft-versus host disease (GvHD), while, so far, four patients did not show any signs of GvHD. Side effects were manageable and limited to the hematopoietic system. Of the three patients achieving CR, two patients relapsed again at extramedullary sites (heart and CNS). Two of these three patients achieving initial CR are alive, one in CR, one in PR, while one patient died due to CNS disease. One of the patients achieving a PR died due to progressive disease, and the other died after a second allogeneic SCT with progressive disease. Median survival of all patients was 125 days (range 39–397 days). Conclusion: Overall, induction of CR after treatment with 5-Aza, and consolidation of CR via DLI followed the 5-Aza treatment is promising.

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