High-dose therapy with autologous or allogeneic transplantation as salvage therapy for small cleaved cell lymphoma of follicular center cell origin

Summary:Although follicular lymphoma (FL) is generally responsive to conventional-dose chemotherapy, improved survival in patients with this disease has been difficult to demonstrate. High-dose chemo/radiotherapy followed by autologous stem-cell transplantation (ASCT) can improve response rates, although its effects on survival remain controversial. Between 1990 and 2003, we transplanted 49 patients with low-grade FL at our institution. Twenty-two patients (45%) had undergone histologic transformation at the time of ASCT. In all, 44 patients (90%) had relapsed disease and five patients (10%) were resistant to chemotherapy at the time of transplantation. After ASCT, 30 patients (61%) were in complete remission (CR). The median overall survival (OS) has not been reached, while the median event-free survival (EFS) is 2.4 years. At a median follow-up of 5.5 years (longest 12.4 years), a plateau has been reached with 56% of patients remaining alive, and 35% event-free. ASCT was well tolerated except for two (4%) treatment-related deaths. In multivariable analysis, CR after ASCT and age less than 60 years are the best predictors of EFS and OS. ASCT is thus a safe therapeutic approach in FL, resulting in long-term EFS and OS for some patients, even with transformed disease. Bone Marrow Transplantation (2005) 36, 955-961.

Section: Discussionmentioning

confidence: 99%

Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma

Andreadis

Schuster

Chong

et al. 2005

“…Details of the transplantation protocols and supportive care are reported elsewhere. 15,16 Evaluation and definitions…”

Section: Transplantation Protocolmentioning

confidence: 99%

“…Allogeneic blood stem cells were mobilized from healthy donors with recombinant granulocyte colony-stimulating factor (G-CSF; Amgen, Thousand Oaks, CA, USA), collected by apheresis and cryopreserved (one patient received non-cryopreserved blood alloSCT). 15,16 Day 0 for the recipient was the day of stem cell infusion. Eighteen recipients of related donor grafts received G-CSF post SCT until neutrophil recovery.…”

Section: Transplantation Protocolmentioning

confidence: 99%

Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia

Pavletić

Arrowsmith

Bierman

et al. 2000

Self Cite

112

Summary:The objective of this study was to describe the outcome of allogeneic stem cell transplantation (alloSCT) in a series of patients with B cell chronic lymphocytic leukemia (B-CLL). Twenty-three B-CLL patients were transplanted between 1988 and 1997 using stem cells from a related (n = 20) or an unrelated donor (n = 3). The median age of the patients was 46 years, and the median number of prior chemotherapy regimens received was two. At transplantation, 14 patients had chemorefractory disease and 12 of these were refractory to fludarabine. The preparative regimens included total body irradiation (TBI) in 22 of the 23 cases. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporine and methotrexate. Twenty patients (87%) achieved a complete remission (CR). The incidence of grade II-IV acute GVHD was 54%. Fourteen (61%) patients are alive and disease-free, including two with unrelated donors, at a median of 26 months (range, 9-115 months). Nine patients (39%) have died, one of whom had progressive B-CLL. The only favorable prognostic factor for failure-free survival (FFS) and overall survival (OS) after alloSCT was the use of a cyclophosphamide/TBI rather than an etoposide/ cyclophosphamide/TBI regimen (P = 0.03). The projected 5-year FFS, OS, and relapse rates after alloSCT were 65% (95% CI, 48-88%), 62% (95% CI, 43-88%), and 5% (95%, CI 0-13%), respectively. These findings demonstrate the potential of high-dose therapy and alloSCT for inducing and maintaining a remission in patients with advanced or chemorefractory B-CLL. The low relapse rate may be due to an allogeneic graft-versus-leukemia effect. Bone Marrow Transplantation (2000) 25, 717-722.

“…It may be necessary to screen for the donor's t(14;18) status before using t(14;18) for monitoring minimal residual disease by RQ-PCR to exclude the possibility of confounding donor's t (14;18) [4][5][6][7][8][9][10][11] Allogeneic stem cell transplantation (allo-SCT) is of increasing interest as a therapeutic option for patients due to the potential of a graft-versus-lymphoma effect to provide long-term disease control. [12][13][14][15] We have recently reported that monitoring the tumor load of t(14;18) cells by real-time quantitative PCR (RQ-PCR) may predict the outcome of FL patients after allo-SCT. 16 Patients with tumor loads of greater than one t(14;18) cell per 10K total cells post transplantation have a higher risk of clinical relapse than those without.…”

Section: Discussionmentioning

confidence: 99%

The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells

Keever-Taylor

Bredeson

et al. 2005

Summary:We performed real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood (PB) and/or bone marrow (BM) samples collected pre-and post transplant from 23 recipient-donor pairs receiving allogeneic stem cell transplantation (allo-SCT) for follicular lymphoma (FL). Of 23 donors, 11 had a PB and/or BM sample positive for t(14;18) (BCL2/IGH fusion) at low levels (oone t(14;18) cell in 10K total cells). Recipients from donors with (n ¼ 11) and those without (n ¼ 12) detectable t(14:18) cells were similar in age, sex, and disease status pretransplant. No differences in the incidence of graft-versus-host-disease (GVHD), delayed engraftment, relapse rate, disease-free survival and overall survival were identified between the groups. Two recipients without detectable t(14;18) cells pretransplant showed detectable t(14;18) cells at 2 and 11 years after receiving grafts from donors with t(14:18) cells. Neither patient developed FL 1.5 and 2 years after the emergence of t(14;18) cells. Although the sample size is relatively small, our findings suggest that individuals carrying t(14;18) cells may not be excluded as donors given the lack of an association of t(14;18) detected in donors with adverse clinical outcome. It may be necessary to screen for the donor's t(14;18) status before using t(14;18) for monitoring minimal residual disease by RQ-PCR to exclude the possibility of confounding donor's t (14;18) [4][5][6][7][8][9][10][11] Allogeneic stem cell transplantation (allo-SCT) is of increasing interest as a therapeutic option for patients due to the potential of a graft-versus-lymphoma effect to provide long-term disease control. [12][13][14][15] We have recently reported that monitoring the tumor load of t(14;18) cells by real-time quantitative PCR (RQ-PCR) may predict the outcome of FL patients after allo-SCT. 16 Patients with tumor loads of greater than one t(14;18) cell per 10K total cells post transplantation have a higher risk of clinical relapse than those without. The monitoring of minimal residual disease (MRD) by RQ-PCR allows for the development of strategies, such as donor lymphocyte infusions to be employed at a stage of molecular relapse in patients whose RQ-PCR results suggest a high likelihood of subsequent clinical relapse.The utility of using RQ-PCR to monitor tumor load or MRD after allo-SCT, however, can be confounded by the presence of t(14;18) cells of donor origin. We recently described the disappearance of a patient's t(14;18) clone early post transplant with the concomitant emergence and long-term persistence of the donor's t(14;18) clone without development of FL. 17 Although it has not been well studied, donor carrying t(14;18) clones detectable by RQ-PCR could theoretically develop into FL in an immunosuppressed recipient who may have a genetic susceptibility to develop FL. In addition, the presence of t(14;18) clones in the donor could serve as a surrogate marker of a stem cell defect and thus affect transplant outcome in some other manner. Thus, the aims of the current ...