Rituximab in vivo purging is safe and effective in combination with CD34-positive selected autologous stem cell transplantation for salvage therapy in B-NHL

High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard approach for chemosensitive, relapsed aggressive non-Hodgkin's lymphoma (NHL). Various conditioning regimens have been used as treatment before ASCT and disease-free (DFS) and overall survival (OS) rates range from 34 to 60% and 26 to 46%, respectively. To date, few comparative randomized trials have been performed and no regimen has demonstrated superiority to another. Reduction of disease relapse remains the major hurdle for improving patient outcome and in vitro and in vivo purging of lymphoma cells has not necessarily enhanced results. Rituximab pre-mobilization and post-transplant appear to provide better response rates with OS approaching 87-91% at 2-3 years. Newer approaches with radioimmunotherapy may raise DFS to 78% and OS to 93%, albeit with short follow-up. Advances in the conditioning regimens and supportive care have reduced transplant-related mortality to less than 10%. In this review we discuss commonly utilized conditioning regimens, describe their pros and cons and address purging and present conditioning strategies. Owing to the poor outcome with conventional chemotherapy in mantle cell, Burkitt's and T-cell lymphoma, we propose the standard approach of frontline ASCT for these high-risk lymphoma patients. Finally, we will present novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity, to improve the outcome of ASCT in NHL patients.

Section: Original Approachmentioning

confidence: 97%

“…Studies using rituximab in the peri-transplant period are summarized in Table 4. Flohr et al 33 conducted a study to evaluate the safety and effectiveness of rituximab in combination with DexaBEAM as mobilization therapy in 27 B-cell lymphoma patients. They showed significant depletion of peripheral B cells without engraftment delays.…”

Section: Original Approachmentioning

confidence: 99%

Autotransplant conditioning regimens for aggressive lymphoma: are we on the right road?

Fernandez

Escalón

Pereira

et al. 2007

“…7 Regimens, such as high-dose cytosine arabinoside, 8,9 HAM (high-dose cytosine arabinoside/ mitoxantrone), 10 and DexaBEAM (dexamethasone/ BCNU/etoposide/cytosine arabinoside/melphalan), 11 have been used in conjunction with rituximab during mobilization procedures, to obtain tumor-free progenitor cells. Although sufficient numbers of PBSC could be obtained using these regimens, the timing of leukapheresis differed with each case, because decisions were based on measurement of CD34 þ cells or platelet recovery in the PB.…”

Section: Discussionmentioning

confidence: 99%

Peripheral blood stem cell mobilization following CHOP plus rituximab therapy combined with G-CSF in patients with B-cell non-Hodgkin's lymphoma

Endo

Sato

Mogi³

et al. 2004

Summary:We mobilized peripheral blood stem cells (PBSC) following CHOP plus rituximab (CHOP-R) therapy, and compared with the findings following CHOP therapy without rituximab. All patients were given G-CSF starting from day 11 after CHOP therapy. Patients in the CHOP-R group (n ¼ 8) were given rituximab on day 12. Target CD34 þ cells number was collected in a single leukapheresis on day 14, from all the eight patients in the CHOP-R group. PBSC mobilization kinetics, CD34þ cells yield and colony-forming ability in the graft collection, toxicity during mobilization, and engraftment after transplantation of CHOP-R group were not significantly different from those in the CHOP group (n ¼ 8). In all patients given CHOP-R therapy, CD20 þ cells and immunoglobulin heavy chain (IgH) rearrangement in the graft collection were undetectable by flow-cytometric analysis and Southern blot analysis, respectively, but with PCR analysis two of eight grafts were positive for IgH rearrangement. While further studies are needed to evaluate the efficacy of purging and the outcome of patients undergoing autologous transplantation, CHOP-R therapy can be safely and effectively used in the mobilization phase of PBSC collection, without excess clinical toxicity or deleterious effect on PBSC mobilization kinetics or engraftment time.

“…Preliminary results of trials utilizing rituximab as in vivo purging prior to ASCT have suggested high molecular response rates. [34][35][36][37] Long-term follow-up of these studies is required to establish PCR as a reliable surrogate marker of clinical response in this situation.…”

Section: Discussionmentioning

confidence: 99%

Ex vivo B cell depletion using the Eligix B Cell SC system and autologous peripheral blood stem cell transplantation in patients with follicular non-Hodgkin's lymphoma

Friedberg

Kim

et al. 2003

Summary:One limitation of ASCT is the potential reinfusion of tumor cells contaminating PBSC. The Eligix B cell SC system consists of high-density microparticles coated with anti-B cell antibodies. To determine if this system eliminates B cells and lymphoma cells from PBSC, immunocytochemistry and PCR of the bcl-2/IgH rearrangement were performed, and correlated with patient outcome after ASCT. Eligible patients (n ¼ 29) had relapsed or transformed follicular NHL with bone marrow involvement o20%, and all lymph nodes o5 cm. PBSCs were mobilized with cyclophosphamide/G-CSF (n ¼ 21), and patients were conditioned with cyclophosphamide, carmustine and etoposide.Using immunocytochemistry on PBSC, the median number of CD20+ cells pre-purge was 310/10 6 (range 0-16692) and post-purge was 0.75/10 6 ; the median log B cell depletion was 2.7 (range 1.4-3.9). B cell depletion correlated with PFS after ASCT (P ¼ 0.06). Of 17 available samples for PCR, only four had a detectable t(14;18) breakpoint. After purging, all four remained PCR+; two had a 1-3 log depletion of lymphoma cells. At median follow-up of 18 months, 10 patients, including five infused with PCR-negative PBSC, have had disease progression. The paucity of PCR-informative patients, possibly related to in vivo rituximab therapy, limited the utility of minimal residual disease as a surrogate marker of clinical outcome.