High-dose therapy and autologous stem cell transplant for transformed non-Hodgkin lymphoma in the rituximab era

James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY , USA.
Leukemia & lymphoma (Impact Factor: 2.61). 12/2011; 53(5):830-5. DOI: 10.3109/10428194.2011.631637
Source: PubMed

ABSTRACT The impact of rituximab on the outcome of high-dose therapy and autologous stem cell transplant (HD-ASCT) for transformed non-Hodgkin lymphoma (NHL) has not been previously described. We analyzed 18 consecutive patients with indolent NHL who transformed to diffuse large B-cell lymphoma (DLBCL), received rituximab-containing therapy either before or after transformation and underwent subsequent HD-ASCT. With a median follow-up of 40 months, the 2-year progression-free survival (PFS) was 59% and the 2-year overall survival (OS) was 82%. Six patients did not receive rituximab pre-transformation. This group had a significantly better PFS at 2 years post-HD-ASCT compared to 12 patients who were exposed to rituximab pre-transformation (p = 0.03). HD-ASCT remains an effective therapeutic option for transformed NHL in the rituximab era. However, patients exposed to rituximab pre-transformation appear to have inferior HD-ASCT outcomes, and thus may benefit from novel conditioning and maintenance regimens in the setting of HD-ASCT.

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    ABSTRACT: Transformation from indolent non-Hodgkin lymphoma (NHL) to diffuse large B cell lymphoma (DLBCL) has historically been associated with a poor prognosis. A small series of autologous stem cell transplantation (ASCT) studies using conventional conditioning regimens has demonstrated durable PFS rates ranging from 25-47%, but data in the rituximab era are lacking. Here we report the results of a multicenter retrospective trial evaluating ASCT in patients with transformed lymphoma using the Z-BEAM conditioning regimen, which combines yttrium-90-labeled ibritumomab tiuxetan (Zevalin) with high dose BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy. A total of 63 patients were treated from four institutions between 2003 and 2011. Histological confirmation of transformation was required and defined as a diagnosis of DLBCL in patients with either a prior history or concomitant diagnosis of low-grade B-cell NHL. Median patient age at ASCT was 59.5 years, median number of prior regimens was 2, and all patients wereexposed to rituximab. Disease status at ASCT was: 1st complete remission (CR) (n=30), 1st partial remission (PR) (n=11), 1st relapse (n=14), and > 2nd CR (n=8). The median time from diagnosis of histological transformation to ASCT was 7.5 months (range 2.8-116 months). Two-year non-relapse mortality was 0 %. Median follow-up for living patients was 28 months (range 5-103). Two-year PFS was 68% (95% CI 58-75) and OS was 90% (95% CI: 80-95). In conclusion, the Z-BEAM conditioning regimen for ASCT is well-tolerated by patients with transformed lymphoma and demonstrates encouraging clinical outcomes.
    Biology of Blood and Marrow Transplantation 12/2014; DOI:10.1016/j.bbmt.2014.07.028 · 3.35 Impact Factor
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    ABSTRACT: Background The role of allogeneic (ALLO) and autologous (AUTO) stem cell transplantation in the management of patients with transformed indolent non-follicular non-Hodgkin lymphoma is unknown. Methods This is a multicenter, retrospective cohort study of patients with biopsy-proven indolent B-cell non-follicular non-Hodgkin lymphoma, and simultaneous or subsequent biopsy-proven aggressive histology transformation who were treated with ALLO or AUTO between 1996-2013. All patients received myeloablative conditioning regimens. Outcomes were compared to a cohort of 246 patients with transformed follicular lymphoma who also underwent ALLO (n=47) or AUTO (n=199) across the same institutions and timeframe. Results Thirty-four patients were identified with the following underlying indolent histologies: 15 (44%) marginal zone lymphoma, 11 (32%) chronic lymphocytic leukemia, 6 (18%) small lymphocytic lymphoma, and 2 (6%) lymphoplasmacytic lymphoma. Patients received various anthracycline or platinum-containing chemotherapy regimens for transformation, incorporating rituximab in 25 (74%). Twelve (35%) subsequently underwent ALLO, while 33 (65%) underwent AUTO. The 3-year OS after transplantation was 67% (ALLO 54%, AUTO 74%), and 3-year PFS was 49% (ALLO 40%, AUTO 54%). The 3-year non-relapse mortality was 14% (ALLO 15%, AUTO 7%). Transplant-related mortality at 100 days was ALLO 17% and AUTO 0%. Adjusted for type of stem cell transplantation, 3-year OS, PFS, and NRM were similar to those of patients with transformed follicular lymphoma receiving ALLO and AUTO (p=0.38, p=0.69, p=0.54 respectively). Conclusions ALLO and AUTO may be reasonable treatments for selected patients with transformed non-follicular indolent lymphoma, although medium-term outcomes and toxicity appear to be more favorable with AUTO.
    Biology of Blood and Marrow Transplantation 11/2014; 20(11). DOI:10.1016/j.bbmt.2014.07.015 · 3.35 Impact Factor
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    ABSTRACT: The optimum follow-up of patients with transformed indolent lymphoma (TrIL) is not well defined. We sought to determine the utility of surveillance positron emission tomography-computed tomography (PET-CT) in patients with TrIL achieving complete metabolic remission (CMR) after primary therapy. We performed a retrospective analysis of patients with TrIL treated at Peter MacCallum Cancer Centre between 2002 and 2012 who achieved CMR after primary therapy who had ≥1 subsequent surveillance PET-CT. Of 55 patients with TrIL, 37 (67 %) received autologous stem cell transplantation as consolidation following chemoimmunotherapy. After a median follow-up of 34 (range 3-101) months, the actuarial 3-year progression-free (PFS) and overall survival (OS) were 77 % (95 %CI 62-86 %) and 88 % (75-94 %), respectively. Of 180 surveillance PET-CT scans, there were 153 true negatives, 4 false positives, 1 false negative, 7 indeterminate and 15 true positives. Considering indeterminate scans as false positives, the specificity of PET-CT for detecting relapse was 94 %, sensitivity was 83 %, positive predictive value was 63 % and negative predictive value was 98 %. All seven subclinical (PET detected) relapses were of low-grade histology; in contrast, all nine relapses with diffuse large B cell lymphoma (DLBCL) were symptomatic. In our cohort of patients with TrIL achieving CMR, PET-CT detected subclinical low-grade relapses but all DLBCL relapses were accompanied by clinical symptoms. Thus, surveillance imaging of patients with TrIL achieving CMR is of limited clinical benefit. PET-CT should be reserved for evaluation of clinically suspected relapse.
    Annals of Hematology 03/2014; 93(7). DOI:10.1007/s00277-014-2040-1 · 2.40 Impact Factor


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