The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia.

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop a clinical practice guideline composed of consensus recommendations on immunotherapy for the treatment of acute lymphoblastic leukemia and acute myeloid leukemia.

Clinical outcome following autologous and allogeneic blood and marrow transplantation for relapsed diffuse large-cell non-Hodgkin's lymphoma.

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.

Chronic lymphocytic leukemia: advances in biology and therapeutics.

Recent advances in our understanding of the biology of chronic lymphocytic leukemia have made it possible to stratify patients according to risk. In addition, advances in the therapy of patients have improved responses and have for the first time allowed for a risk adapted approach to patients with chronic lymphocytic leukemia similar to that which has been used for acute leukemia for years. Tumor cell differentiation status and presence of specific somatic and immunoglobulin gene mutations have been shown to be reliable predictors of disease behaviors. This knowledge could provide clinicians with tools to better stratify patients and eventually affect their clinical outcomes. Furthermore, new therapeutic agents and treatment combinations that appear to have increased efficacy have been developed.

Chemotherapy and bone marrow reserve: lessons learned from autologous stem cell transplantation.

Cytotoxic chemotherapy is often complicated by hematopoietic toxicity. The degree of aplasia and the rapidity of count recovery following chemotherapy are indicative of bone marrow reserve. Patients who generally have a normal bone marrow function will recover from chemotherapy-induced cytopenia relatively rapidly. In contrast, patients that have poor bone marrow reserve will have significantly prolonged period of aplasia. Predicting the hematopoietic toxicity of radioimmunotherapy is an important dosimetry consideration. Unfortunately, there are no good models for predicting toxicity from chemotherapy that could be applied to radioimmunotherapy. However, models used to predict the ability to harvest autologous stem cells for use after high dose chemotherapy may be useful in predicting bone marrow reserve and potential toxicity from radioimmunotherapy. These models indicate that the successful mobilization of stem cells into the peripheral blood is inversely proportional to exposure to stem cell toxic drugs. Establishing criteria that will help predict the amount of myelotoxicity sustained from radioimmunotherapy could lead to improved dosimetry and ultimately to better therapy for patients.

Monoclonal antibody therapy with autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

BACKGROUND: With the introduction of novel monoclonal antibody products into the clinic, significant new strategies are being developed to improve upon existing treatment for non-Hodgkin's lymphoma. METHODS: Monoclonal antibodies are being used alone, in combination with chemotherapy, or as adjuncts to autologous bone marrow transplantation for the purpose of purging bone marrow of neoplastic cells. RESULTS: Monoclonal antibodies when used in vivo in conjunction with autologous bone marrow transplantation have been relatively well tolerated. Results from several trials seem to demonstrate a therapeutic benefit for the use of such combinations. CONCLUSIONS: Before these agents can be included in standard bone marrow transplantation regimen, long-term survival outcomes need to be obtained from randomized trials. We review the results from recent trials using monoclonal antibodies in conjunction with autologous stem cell transplantation for the treatment of non-Hodgkin's lymphoma.