Autologous and allogeneic stem cell transplantation for diffuse large cell lymphoma (NHL) – pro

Summary: NHL is currently the second most frequent indication for autologous hematopoietic stem cell transplantation. It is not a useful treatment option for all patients with NHL, but in certain circumstances, autologous stem cell transplantation does provide patients the best opportunity for cure.

Diffuse large-cell lymphoma is the most common form of NHL, and autologous stem cell transplantation has been shown to be beneficial in some subsets with this illness. For patients with diffuse large-cell lymphoma who relapse from a CR but remain chemotherapy-responsive, autologous transplantation is the treatment of choice. The most significant study supporting transplantation is the PARMA study by Philip et al. Patients were randomized to autologous stem cell transplantation versus conventional-dose chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP) if the patient responded to two initial cycles of DHAP. The event-free survival at 5 years was 46% for the transplant arm and 12% for the conventional therapy arm (p = 0.001). Overall survival was 53% for transplant and 32% for the conventional therapy group (p = 0.038). In addition to transplant being shown to be beneficial in this group of patients, additional analysis has demonstrated that an initial remission of fewer than 12 months is an adverse prognostic indicator.

There are also trials that have found contradictory results. Reyes et al. in the LNH93-3 trial randomized 370 patients to standard chemotherapy or autologous transplantation after an abbreviated standard-dose induction regimen. They found the 3-year event-free survival for the hematopoietic stem cell transplant group was 41% versus 54% for the standard therapy arm (p = 0.01). Overall survival was also in favor of standard therapy with 63% disease-free survival versus 47% in the transplanted group (p = 0.003) [62]. A trial by Verdonck et al. randomized 69 patients who had achieved a partial response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to additional CHOP or autologous bone marrow transplantation. The 4-year event-free survival was 53% for the CHOP arm and 41% for the transplantation arm. Disease-free survival at 4 years was 72% for the CHOP group and 60% for transplantation. The reason for the disrepancy is not well understood but these were smaller studies than the PARMA study.

At the present time, high-risk patients who achieve a CR after a full course of standard-dose chemotherapy and have a high risk for relapse may derive the most benefit from stem cell transplantation. The second accepted group is those who evidence chemoresponsiveness after relapse and this is stated in the NCCN guidelines. No additional trials are planned and the Parma results have been accepted as standard therapy.

2011 NCCN on p. BCEL-6 recommends an autologous transplant.

As far as allogeneic, a recent guideline says: “Allogeneic stem cell transplantation is an option for eligible chemosensitive patients with refractory or relapsed AH-NHL who are not candidates for autologous stem cell transplantation or who have a syngeneic (identical twin) donor.” NCCN BCEL-6(2011) says tha llogeneic transplantation is in selected cases and a note explains that such cases include mobilization faiure and persiistent bone marrow invovlement”.  All in all, I consider guidelines to mildy support allogeneic transpalntation for relapsed DLCL.

For patients who failed an autologous transplant, 2012 ESMO guideline says: “Allogeneic stem cell transplantation (allo-SCT) should be considered in selected patients failing autologous stem cell transplantation or with very poor risk factors at relapse”.

H. Bertz, R. Zeiser, W. Lange, S. Fetscher, C. F. Waller, and J. Finke
Long-term follow-up after high-dose chemotherapy and autologous stem-cell transplantation for high-grade B-cell lymphoma suggests an improved outcome for high-risk patients with respect to the age-adjusted International Prognostic Index
Ann. Onc., September 1, 2004; 15(9): 1419 – 1424.

M. D. Caballero, J. A. Perez-Simon, A. Iriondo, J. J. Lahuerta, J. Sierra, J. Marin, M. Gandarillas, R. Arranz, J. Zuazu, V. Rubio, A. Fernandez de Sevilla, E. Carreras, J. Garcia-Conde, J. Garcia-Larana, C. Grande, A. Sureda, M. J. Vidal, J. Rifon, C. Perez-Equiza, R. Varela, J. M. Moraleda, J. C. Garcia Ruiz, C. Albo, R. Cabrera, J. F. San Miguel, and E. Conde
High-dose therapy in diffuse large cell lymphoma: results and prognostic factors in 452 patients from the GEL-TAMO Spanish Cooperative Group
Ann. Onc., January 1, 2003; 14(1): 140 – 151.

S. A. Mink and J. O. Armitage
High-Dose Therapy in Lymphomas: A Review of the Current Status of Allogeneic and Autologous Stem Cell Transplantation in Hodgkin’s Disease and Non-Hodgkin’s Lymphoma
Oncologist, June 1, 2001; 6(3): 247 – 256.

nccn.org, 2011.

Imrie K, Rumble RB, Crump M, Advisory Panel on Bone Marrow and Stem Cell Transplantation, Hematology Disease Site Group. Stem cell transplantation in adults: recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; 2009 Jan 30. 78 p. (Recommendation report; no. 1). [66 references]

Vikas Gupta et al, Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns Blood February 24, 2011 vol. 117 no. 8 2307-2318

van Kampen RJW, Canals C, Schouten HC, et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-hodgkin’s lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European group for blood and marrow transplantation registry. J Clin Oncol 2011;29:1342-1348.

Thomson KJ, Morris EC, Bloor A, et al. Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-hodgkin’s lymphoma. J Clin Oncol 2009;27:426-

 

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