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Abstract: The results of blood or marrow transplantation in patients with chemorefractory aggressive lymphoma, that is, those not responding to conventional-dose chemotherapy at the time of transplant, have been poor. The relapse rate has been high after autologous bone marrow transplant, whereas allogeneic transplantation has been associated with excessive transplant-related toxicity. Administration of cyclosporine after autologous transplantation can induce an autoreactive syndrome that resembles graft-versus-host disease (GVHD). This syndrome, named autologous graft-versus-host disease, has clear antitumor activity in animal models that can be enhanced by the addition of cytokines such as γ-interferon and interleukin-2. A randomized, prospective study was conducted to evaluate the antitumor effect of autologous graft-versus-host disease induced with cyclosporine, and augmented by the administration of γ-interferon and interleukin-2 in patients with chemorefractory Hodgkin and aggressive non-Hodgkin lymphomas. Fifty-one patients were randomized, 24 to the autologous GVHD induction arm, and 27 to the noninduction arm after autologous transplant using mobilized peripheral blood stem cell (PBSC) grafts. There were no differences in treatment-related mortality, overall and event-free survival (OS, EFS) between both groups; however, in the induction arm, GVHD developed only in 4 patients. The administration of oral cyclosporine followed by interleukin-2 and γ-interferon is generally not well tolerated, and does not appear to be an effective method to induce autologous GVHD in patients receiving autologous PBSC grafts. [Copyright &y& Elsevier]

Abstract: High-dose chemotherapy followed by blood or marrow transplantation (BMT) is generally considered the best salvage option for patients with relapsed diffuse large–B-cell non-Hodgkin’s lymphoma (DLCL). The relative roles for allogeneic and autologous BMT remain controversial. We reviewed the clinical outcome of 183 patients with relapsed DLCL who underwent BMT at Johns Hopkins University in 1985-2001. A total of 45 patients received T-cell–depleted HLA-matched allogeneic bone marrow (allo-BMT), and 138 patients received autologous marrow or peripheral blood stem cells (auto-BMT). The allo-BMT recipients had a higher proportion of patients with chemoresistant disease (P = .004) and had received more chemotherapy before BMT (P = .02). The auto-BMT recipients were older (P < .001) and were of more advanced-stage disease (P = .01). The 3-year overall survival (OS) was 23.7% (median survival, 129 days) after allo-BMT and 33.1% (median survival, 263 days), after auto-BMT (log-rank, P = .17). The 3-year OS for patients with sensitive disease was 51.9% after allo-BMT and 46.2% after auto-BMT (log-rank, P = .38). For patients with resistant disease, the 3-year OS was 12.1% after allo-BMT and 19.1% after auto-BMT (log rank, P = .08). In multivariate analysis, significant predictors of death were disease sensitivity (hazard rate [HR], 0.3; 95% confidence interval [CI] 0.2-04; P < .001), age >40 years (HR, 2.42; 95% CI, 1.7-3.4; P < .001), and stage at diagnosis (HR, 1.2; 95% CI, 1.0-1.4; P = .04). The 3-year event-free survival (EFS) for patients with sensitive disease was 52.7% after allo-BMT and 42.0% after auto-BMT (log-rank, P = .29). For patients with resistant disease, the 3-year EFS was 6.2% after allo-BMT and 19.4% after auto-BMT (log-rank, P = .1). The 3-year probability of relapse for chemosensitive patients was 30% after allo-BMT and 46.1% after auto-BMT (log-rank, P = .25). The 3-year relapse rate in patients with resistant disease was 75.0% after allo-BMT and 69.9% after auto-BMT (log-rank, P = .58). In multivariate analysis, only disease sensitivity status (HR, 0.4; 95% CI, 0.2-2.1; P < .001) and age >40 years (HR, 1.7; 95% CI, 1.1-2.9; P = .03) appear to have a significant impact on relapse. Transplant-related mortality (TRM) was the cause of death for 51.1% of allo-BMT recipients and 23.9% of auto-BMT recipients (P < .001). Mortality from lymphoma was 26.6% in allo-BMT recipients and 43.5% in auto-BMT recipients (P = .02). Auto-BMT and allo-BMT produced similar survival for patients with relapsed DLCL. For patients with sensitive disease, allo-BMT seemed to provide longer survival with less relapse; however, this was achieved at the cost of greater TRM. [Copyright &y& Elsevier]

Abstract: We retrospectively analyzed 83 consecutive recipients of donor lymphocyte infusions (DLI) after allogeneic transplantation for factors associated with disease response and graft-versus-host disease (GVHD). DLI was highly effective in relapsed chronic phase chronic myeloid leukemia (CML), with 71% of patients achieving durable complete remissions (CR). In relapsed acute myeloid leukemia, DLI led to durable CRs in 31% of patients; the rate was <20% in all other diseases. Achieving full donor chimerism and GVHD were predictive of CR. Grade II or higher acute or chronic GVHD occurred in 36 (43%) patients and contributed to death in 13 (16%). Even more patients, 33 (40%), died of their underlying malignancy, including 10 who developed active GVHD. In relapsed CML, most durable CRs occurred without clinically apparent GVHD, yet all responders achieved full donor chimerism, including 6 with coincident normal host hematopoiesis at the time of DLI. Thus, in CML, potent lymphohematopoietic graft-versus-host reactions occurred even in the absence of clinically apparent GVHD; this confirms the ability to dissociate these processes and argues against a leukemia-specific immunologic effect. DLI clearly has efficacy in the treatment of relapsed disease after allogeneic transplantation. However, with the exception of CML, most patients die of their underlying disease because of insufficient antitumor activity even with active GVHD. [Copyright &y& Elsevier]

Abstract: To evaluate high-dose therapy and autologous or allogeneic blood or marrow transplantation (BMT) for mantle cell lymphoma, patients receiving BMT for newly diagnosed or relapsed mantle cell lymphoma were identified through the registry at Johns Hopkins. The pathologic diagnostic criteria were reviewed, and details of the presentation, transplant procedure, and survival outcomes were determined. Fifty-eight patients were identified, of whom 64% underwent transplantation in first remission and 12% had primary induction failure. Nineteen patients (one third) received an allograft. Preparative regimens consisted of cyclophosphamide in combination with either busulfan or total body irradiation. On multiple regression analysis, transplantation after 1 or more relapses (hazard ratio, 2.98; P = .02), primary induction failure (hazard ratio, 5.39; P = .002), and allogeneic transplantation (hazard ratio, 3.03; P = .007) were associated with an inferior event-free survival (EFS). However, EFS curves were not statistically different for autologous and allogeneic BMT performed in first remission, with an estimated 3-year EFS approaching or equaling 70%. Primary induction failure and residual bone marrow involvement were the only statistically significant predictors of relapse on multiple regression analysis. At 3 years, the estimated EFS for the entire cohort after BMT was 51%, the probability of relapse was 31%, and the overall survival was 59%. The benefit of autologous or allogeneic BMT for mantle cell lymphoma is thus most apparent when transplantation is performed in first remission. Whether allogeneic BMT ultimately confers an advantage because of a graft-versus-lymphoma effect remains to be determined. [Copyright &y& Elsevier]