Amin Alousi

Nonmyeloablative stem cell transplantation in patients with follicular lymphoma has been designed to exploit the graft-versus-lymphoma immunity. The long-term effectiveness and toxicity of this strategy, however, is unknown. In this prospective study, we analyzed our 8-year experience. Patients received a conditioning regimen of fludarabine (30 mg/m(2) daily for 3 days), cyclophosphamide (750 mg/m(2) daily for 3 days), and rituximab (375 mg/m(2) for 1 day plus 1000 mg/m(2) for 3 days). They were then given an infusion of human leukocyte antigen-matched hematopoietic cells from related (n = 45) or unrelated donors (n = 2). Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Forty-seven patients were included. All patients experienced complete remission, with only 2 relapses. With a median follow-up time of 60 months (range, 19-94), the estimated survival and progression-free survival rates were 85% and 83%, respectively. All 18 patients who were tested and had evidence of JH/bcl-2 fusion transcripts in the bone marrow at study entry experienced continuous molecular remission. The incidence of grade 2-IV acute GVHD was 11%. Only 5 patients were still undergoing immunosuppressive therapy at the time of last follow-up. We believe that the described results are a step forward toward developing a curative strategy for recurrent follicular lymphoma.

To develop a novel acute graft-versus-host disease (GVHD) risk score, we examined the GVHD clinical stage and grade of 1723 patients at the onset of treatment with systemic steroids. Using clinical grouping, descriptive statistics and recursive partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the number of involved organs and severity of GVHD at onset. The overall response (complete response/partial response) rate 28 days after initiation of steroid therapy for acute GVHD was lower in the 269 patients with HR-GVHD than in the 1454 patients with standard risk (SR)-GVHD (44% [95% confidence interval (CI) 38% to 50%] versus 68% [95% CI, 66% to 70%], P < .001). Patients with HR-GVHD were less likely to respond at day 28 (odds ratio [OR], .3; 95% CI, .2 to .4; P < .001) and had higher risks of mortality (relative risk, 2.1; 95% CI, 1.7 to 2.6; P < .001) and transplant-related mortality (relative risk, 2.5; 95% CI, 2.0% to 3.2%, P < .001) than patients with SR-GVHD. This refined definition of acute GVHD risk is a better predictor of response, survival, and transplant-related mortality than other published acute GVHD risk scores. Patients with HR-GVHD are candidates for studies investigating new treatment approaches. Likewise, patients with SR-GVHD are candidates for studies investigating less toxic therapy.

Patients with steroid-resistant acute graft versus host disease (aGVHD) have a dismal prognosis, with mortality rates in excess of 90%. We sought to identify a subgroup of patients less likely to benefit from initial therapy with corticosteroids as well as the impact of response on day 14 on outcome. Retrospective evaluation was performed of patients with biopsy-proven aGVHD treated with corticosteroids after allogeneic HSCT at M.D. Anderson Cancer Center from 1998 through 2002 (N = 287). Overall response to first-line therapy on day 14 was 56%. Grade III-IV aGVHD and hyperacute GVHD were the most significant factors predicting failure. Patients who fail to respond to steroids by day 14 should be considered for clinical trials. Severity of aGVHD, hyperacute GVHD, and sex mismatch could be integrated into prognostic scoring systems which may allow for pretreatment identification of patients unlikely to benefit from standard therapy with corticosteroids.

In this study, we analyzed the long-term outcome of a risk-adapted transplantation strategy for mantle cell lymphoma in 121 patients enrolled in sequential transplantation protocols. Notable developments over the 17-year study period were the addition of rituximab to chemotherapy and preparative regimens and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In the autologous transplantation group (n = 86), rituximab resulted in a marked improvement in progression-free survival for patients who received a transplant in their first remission (where a plateau emerged at 3-8 years) but did not change the outcomes for patients who received a transplant beyond their first remission. In the NST group, composed entirely of patients who received a transplant beyond their first remission, durable remissions also emerged in progression-free survival at 5 to 9 years. The major determinants of disease control after NST were the use of a peripheral blood stem cell graft and donor chimerism of at least 95%, whereas the major determinant of death was immunosuppression for chronic graft-versus-host disease. Our results show that long-term disease-free survival in mantle cell lymphoma is possible after rituximab-containing autologous transplantation for patients in first remission and after NST for patients with relapsed or refractory disease.