Immunomodulatory nonablative conditioning regimen for B-cell lymphoid malignancies

Abstract

Twenty-six patients with recurrent CD20+ B-cell lymphoid malignancies received fludarabine, cyclophosphamide, and rituximab–based nonablative conditioning followed by either matched related (n = 18) or unrelated (n = 8) donor allogeneic stem cell transplantation (allo-SCT) between March 2008 and May 2011. Median age of patients at transplantation was 59 years (range, 41–64 years). At diagnosis, 20 (77%) had stage IV disease; 23 (88%) received ≥3 regimens, 14 (54%) received ≥4 regimens, and 4 (15%) had earlier autologous-SCT. All patients had either chemosensitive or stable disease and nine (35%) were in complete remission before transplantation. At the time of analysis, 17 patients were alive with an estimated 2-year overall survival and progression-free survival rate of 63% and nonrelapse mortality of 25%. Grade II to IV acute graft-vs-host-disease occurred in 8 (31%) and chronic graft-vs-host-disease in 6 (23%) patients (extensive, n = 3). Causes of death include progressive disease in four, acute graft-vs-host-disease in two (both after receiving donor lymphocyte infusion for mixed chimerism with residual disease), infection in one, and other (e.g., substance abuse, leukoencephalopathy) in two. Six patients required rehospitalization within 100 days of SCT (mean = 10 days; range, 3–18 days). Our data support fludarabine, cyclophosphamide, and rituximab–based nonablative conditioning allo-SCT in CD20+ B-cell lymphoid malignancies and it is time to compare this regimen with an alternative reduced-intensity conditioning regimen in B-cell malignancies.

Outcomes of autologous or allogeneic stem cell transplantation for non-Hodgkin lymphoma

“…Among several RIC regimens, FCR regimen followed by either related or unrelated donor allo-SCT is safe and effective in B cell lymphoid malignancy. 5;21;22 A recently published MDACC study showed excellent PS and OS (85% and 83%, respectively, after a median follow-up of 60 months) for relapsed FL after FCR RIC allo-SCT. 22 The incidence of grade II-IV acute GVHD (aGVHD) was only 11%.…”

“…We have also recently reported our results using FCR RIC allo-SCT in patients with CD20+ B-cell lymphoid malignancies with improved outcome and low GVHD and NRM. 5 Lower intensity conditioning regimens have therefore been extended to older patients. As expected, subjects with more advanced disease and more aggressive histologies had greater risk of relapse.…”

“…12;14;18;19 Reduced-intensity conditioning (RIC) and non-myeloablative conditioning (NST) regimens are increasingly used in patients with NHL. 5;6;20 These lower-intensity conditioning regimens (RIC or NST) reportedly have lower non-relapse mortality (NRM) and can be used in older patients with comorbidities. Lower-intensity regimens for allo-SCT use lower doses of conditioning chemotherapy and radiation and rely on an immune-mediated GVL effect for disease control.…”

Allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders

“…Hematopoietic Stem cell transplantation (HSCT) is frequently considered for eligible patients with non-Hodgkin lymphoma (NHL). 1 , 2 , 3 , 4 , 5 , 6 Autologous HSCT (auto HSCT) is recommended for patients with either relapsed NHL or those in first remission as consolidative therapy. NHL patients are usually considered for allogeneic HSCT (allo HSCT) because of the high rate of relapse seen even after chemotherapy and auto HSCT, and the potential benefit of a graft-versus-lymphoma (GvL) effect after allo HSCT.…”

“…Reduced-intensity conditioning (RIC) regimens are being increasingly used in patients with NHL. 5 , 6 , 16 These lower-intensity conditioning regimens reportedly have lower NRM, and can be used in older patients with comorbidities. Lower-intensity regimens for allo HSCT use lower doses of conditioning chemotherapy and radiation and rely on an immune-mediated GvL effect for disease control.…”