Allogeneic bone marrow transplantation for refractory mantle cell lymphoma

Hoffknecht, M.; Krüger, William; Zeller, W.; Renges, Helmut; Zschaber, R.; Zander, Axel R.

doi:10.1007/s002770000196

Cited by 25 publications

(11 citation statements)

References 6 publications

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“…All three elderly patients who had relapsed after autologous transplant remain disease free after a second, reducedconditioning allogeneic transplant. Although apparent cures of MCL with allogeneic transplant after autologous transplant failure have been described in case reports, [22][23][24] these patients were conditioned with high-dose therapy regimens. Khouri et al 25 have also described a potent GVL effect in MCL.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin's lymphoma

Seropian

Bahceci

Cooper

2003

Bone Marrow Transplant

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Summary:A high incidence of nonrelapse mortality (NRM) has limited the use of allogeneic transplantation for poor prognosis non-Hodgkin's lymphoma (NHL). We sought to improve the outcome of allografting by utilizing Filgrastim-mobilized peripheral blood stem cells (PBSC) in combination with either standard ablative or reducedintensity conditioning. A total of 21 patients with intermediate/high-grade lymphoma and seven patients with low-grade histology were enrolled on protocols using PBSC. All patients were considered high risk for recurrence and/or NRM because of age 450 (n ¼ 16), refractory disease (n ¼ 17), failed autologous transplant (n ¼ 11) and abnormal organ function (n ¼ 2). In all, 17 patients received ablative regimens and 11 received modified conditioning including fludarabine, intravenous busulfan and ATG. Tacrolimus and mini-dose methotrexate were used for graft-versus-host-disease (GVHD) prophylaxis. Median follow-up was 38 months. Diseasefree and overall survival were 57 and 58%. Seven of the 11 patients who relapsed after a previous transplant remain disease free. Four of the 10 patients with recurrent/ persistent disease post transplant responded to additional therapy including withdrawal of immunosuppression7 DLI. These results support a potent graft-versus-lymphoma effect and suggest that patients who relapse after an autologous transplant can be salvaged with an allogeneic transplant.

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Section: Discussionmentioning

confidence: 99%

Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin's lymphoma

Seropian

Bahceci

Cooper

2003

Bone Marrow Transplant

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“…9,17,18 However, highdose allogeneic HCT was associated with a 30% to 40% risk of early nonrelapse mortality, which has tempered enthusiasm for exploring this approach in patients with mantle cell lymphoma, especially in those who previously failed autologous HCT. [19][20][21][22] More recently, promising results have been seen with reducedintensity conditioning and allogeneic HCT in chemotherapy responsive patients 23 compared with more advanced-stage patients.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma

Maris

Sandmaier

Storer

et al. 2004

Blood

245

134

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We carried out HLA-matched related (n ‫؍‬ 16) and unrelated (n ‫؍‬ 17) hematopoietic cell transplantation (HCT) in 33 patients with relapsed and refractory mantle cell lymphoma after nonmyeloablative conditioning with fludarabine and 2 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Fourteen patients had failed high-dose autologous HCT. Of the 33 patients studied, 31 had stable engraftment, whereas 2 patients experienced nonfatal graft rejections. The incidences of acute grades II, III, and IV, and chronic graft-versus-host disease (GVHD) were 27%, 17%, 13%, and 64%, respectively. The overall response rate in the 20 patients with measurable disease at the time of HCT was 85% (n ‫؍‬ 17; 75% complete remissions [CR] and 10% partial remissions [PR]), whereas 3 patients had progressive disease. Only one of the 17 patients who responded and none of the 13 who received transplants in CR had disease relapse with a median follow-up of 24.6 months. Relapse and nonrelapse mortalities were 9% and 24%, respectively, at 2 years. The Kaplan-Meier probabilities of overall and disease-free survivals at 2 years were 65% and 60%, respectively. Allogeneic HCT after nonmyeloablative conditioning is a promising salvage strategy for patients with relapsed and refractory mantle cell lymphoma. The high response and low relapse rates with this approach suggest that mantle cell lymphoma is susceptible to graft-versus-tumor responses. (Blood.

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“…Different small series suggested that the induced graft-versus-lymphoma effect is able to achieve long-lasting complete remissions, even in patients with relapsed MCL [41][42][43]. Because transplant-related toxicity is high, a dose-reduced regimen adapted to the elderly patient with MCL cohort may be applied.…”

Section: Lymphocyte-specific Antibodiesmentioning

confidence: 98%

Mantle cell lymphoma: Therapeutic strategies are different from CLL

Hiddemann

Dreyling

2003

Curr. Treat. Options in Oncol.

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In contrast to the typical course of chronic lymphocytic lymphoma and despite an indolent lymphoma-like presentation, the clinical outcome of mantle cell lymphoma (MCL) is dismal, with a median survival time of 3 years and virtually no long-term survivors. Most patients are diagnosed with advanced stage III/IV disease. Although clinical studies did not prove a clear superiority of anthracyclin-containing combinations, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimens represent the standard therapeutic approach in MCL. Recent randomized studies have shown a benefit of a combined immunochemotherapy strategy (chemotherapy plus rituximab) increasing the complete and overall response rates, whereas further follow-up is pending for evaluation of the progression-free and overall survival. In patients younger than 65 years, a dose-intensive consolidation comprising high-dose radiochemotherapy and subsequent autologous stem cell transplantation after a CHOP-like induction results in an improved progression-free survival. However, despite the benefits of this multimodal approach, most patients relapse even after high-dose therapy. The only curative approach is allogeneic stem cell transplantation, which may be adapted to the elderly MCL patient cohort by modified dose-reduced conditioning regimens. Prospective randomized trials remain critical to further improve the clinical course of MCL with the addition of newer treatment modalities, such as radioactively labeled antibodies and targeted therapies (eg, flavopiridol and PS-341).

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Allogeneic bone marrow transplantation for refractory mantle cell lymphoma

Cited by 25 publications

References 6 publications

Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin's lymphoma

Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin's lymphoma

Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma

Mantle cell lymphoma: Therapeutic strategies are different from CLL

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