Low incidence of secondary neoplasia after autotransplantation for lymphoproliferative disease: the role of pre‐transplant therapy

Abstract

To asses the real contribution of pre-transplantation treatment in the incidence of secondary neoplasia after autologous transplant for lymphoproliferative disorders, we used stringent inclusion/exclusion criteria. One hundred and forty-two patients out of 323 that underwent autologous transplantation for lymphoproliferative disorders were studied. The risk factors that were evaluated with univariate and multivariate analysis included: gender, sex, age, diagnosis, radiotherapy, and chemotherapy prior to conditioning regimen, disease status at peripheral blood stem-cell transplantation (PBSCT) and type of harvest. Three patients developed secondary myelodysplastic syndrome/acute myeloid leukemia (sMDS/AML) and three patients developed solid neoplasia. By univariate analysis diagnosis chronic lymphocytic leukemia and use of fludarabine and monoclonal antibodies were the only variables significantly associated with the development of sMDS/AML. By multivariate analysis, the variables associated with sMDS/AML were the use of fludarabine and disease status at PBSCT. By univariate analysis, we found that radiotherapy and the use of monoclonal antibodies were significantly associated with the development of secondary solid neoplasia. Multivariate analysis confirmed that the only two variables significantly associated with new cancers were radiotherapy and prior treatment with monoclonal antibodies. We report the lowest incidence of sMDS/AML after autologous stem-cell transplantation for lymphoproliferative malignancies. Major reasons could be ascribed to the stringent inclusion/exclusion criteria used to establish the real incidence of sMDS/AML because of chemo-radiotherapy used before transplant procedure. The low incidence of secondary solid tumors could be caused by the absence of total body irradiation as part of the conditioning regimen or the short follow-up.

Fludarabine as a risk factor for poor stem cell harvest, treatment-related MDS and AML in follicular lymphoma patients after autologous hematopoietic cell transplantation

“…Laurenti et al 21 evaluated the role of pre-transplant chemotherapy in the incidence of secondary malignancies after auto-HCT for indolent lymphoma. Out of 142 patients, 3 patients developed t-MDS/AML and use of fludarabine was found to be an independent risk factor for development of t-MDS/AML in both univariable and multivariable analyses.…”

Up-front fludarabine impairs stem cell harvest in multiple myeloma: report from an interim analysis of the NMSG 13/03 randomized placebo controlled phase II trial

“…All other variables registered showed no difference including performance score. Many clinical trials in CLL have shown the combination of fludarabine and cyclophosphamide to have tolerable toxicity, 13–15 however, the observed significant reduction in renal function may be due to latent myeloma specific kidney impairment. All serious adverse events were reported to The Trial Secretariat within one working day of discovery or notification of the event.…”

“…Recently, the stem cell toxicity has been supported by the observation that the risk for sMDS/AML was correlated to the use of fludarabine based on an unknown mechanism. 15 …”