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Reduced-intensity conditioning allogeneic transplantation is associated with a high incidence of extramedullary relapses in multiple myeloma patients

Leukemia volume 20, pages 542–545 (2006)Cite this article

Autologous stem cell transplantation (ASCT) has become the standard of care for young patients diagnosed with multiple myeloma (MM). Nevertheless, the median duration of response after ASCT does not exceed 3 years, and almost all patients ultimately relapse. By contrast, allogeneic transplantation has led to a long-term disease-free survival in a fraction of MM patients.1 Unfortunately, allogeneic transplantation has been associated with a high transplant-related mortality (TRM), ranging from 30 to 50% in the first 180 days.2 In order to overcome this high mortality, new approaches using nonmyeloablative or reduced-intensity conditioning (RIC) regimens have been designed, in an effort to reduce the toxicity associated with the high doses of chemotherapy, but maintaining the graft-versus-myeloma (GVM) effect.3 Nevertheless, the low TRM observed using this approach is partially overwhelmed by the high relapse rate reported among high-risk patients, such as those carrying chromosome abnormalities (del 13) or those relapsing after a previous ASCT.4, 5 On the other hand, the European Blood and Marrow Transplantation (EBMT) study group has reported a decrease in TRM from 46 to 33% in MM patients undergoing myeloablative allogeneic transplantation prior to or after 1993.6 In addition, new treatment strategies based on thalidomide/IMIDs and proteasome inhibitors are demonstrating a high efficacy in terms of disease control in refractory MM patients. Thus, with the new therapeutic armamentarium available for MM patients, results on the long-term outcome are required in order to better define the role of allo-RIC in the management of MM.

In the current study, we analyzed the efficacy of allo-RIC in a series of 70 MM patients enrolled in the Spanish allo-RIC program between May 1999 and August 2004. Median age was 54 years (30–66 years). All patients received peripheral blood progenitor cells (PBPC) from an MRD, and all but six had received a previous autologous transplant (ASCT). In total, 15 patients were included in a sequential ASCT-allo-RIC approach. Overall, 33 patients had either relapsed (n=29) or did not respond (n=4) to prior ASCT. Disease status at transplant was complete remission (CR) in 5 (7.1%) patients, partial response (PR) in 37 (52.9%) patients, stable disease (SD) in 7 (10%) patients and progressive disease (PD) in 21 (30%) patients. All but three patients were conditioned with fludarabine 30 mg/m2 intravenously (i.v.) on days −8 to −4 followed by melphalan 70 mg/m2 i.v. on days −3 and −2 (n=39) or on day −2 (n=28). Two patients received busulphan 10 mg/m2 instead of melphalan and one patient received 200 cGy TBI. Standard graft-versus-host disease (GVHD) prophylaxis consisted of conventional doses of cyclosporine A (CsA) plus three (n=18) or four doses of MTX (n=50). Two patients received CsA plus ATG.

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Authors and Affiliations

  1. Hospital Clínico Universitario, Salamanca, Spain

    J A Pérez-Simón, D Caballero, C Cañizo, L Vazquez & J F San Miguel

  2. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    A Sureda, R Martino, S Brunet, A García & J Sierra

  3. Hospital Clinic i Provincial, Barcelona, Spain

    F Fernández-Aviles & L Rosiñol

  4. Hospital Son Dureta, Barcelona, Spain

    A Sampol

  5. Hospital Puerta de Hierro, Madrid, Spain

    J R Cabrera

  6. Instituto Catalán de Oncología, Barcelona, Spain

    J Petit

  7. Fundacion Jimenez Diaz, Madrid, Spain

    J F Tomás

  8. Hospital Morales Meseguer, Murcia, Spain

    J M Moraleda

  9. Hospital de la Princesa, Madrid, Spain

    A Alegre

  10. Hospital 12 de Octubre, Madrid, Spain

    J Lahuerta

  11. Hospital Gregorio Marañón, Madrid, Spain

    J L Díez-Martín

  12. Hospital de Jerez, Jeréz, Spain

    A León

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  1. J A Pérez-Simón
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  21. J F San Miguel
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on behalf of the GEM (Grupo Español de Mieloma)

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Correspondence to J A Pérez-Simón.

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Pérez-Simón, J., Sureda, A., Fernández-Aviles, F. et al. Reduced-intensity conditioning allogeneic transplantation is associated with a high incidence of extramedullary relapses in multiple myeloma patients. Leukemia 20, 542–545 (2006). https://doi.org/10.1038/sj.leu.2404085

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