Efficacy of nivolumab as checkpoint inhibitor drug on survival rate of patients with relapsed/refractory classical Hodgkin lymphoma: a meta-analysis of prospective clinical study.

AIMS: The primary standard treatment for classic Hodgkin's lymphoma (cHL) is chemotherapy and radiation therapy. However, some patients get relapsed, or their diseases become resistant. PD1 blocking antibodies have been used to increase the response of treatment in solid tumors, and led to potentially stable responses that are acceptable. Our purpose in this study is to investigate the effect of nivolumab as a PD1 blocking antibody on the survival rate of patients with Hodgkin's cancer. METHODS: Databases were found in International Medical Sciences, Web of Science, Medline, Scopus, Index Copernicus, PubMed, DOAJ, Google Scholar, EBSCO-CINAHL, and Persian databases containing SID and Magiran using keywords such as: "checkpoint inhibitor", "nivolumab", "Hodgkin lymphoma", and "PD1 Blockade". The risk of bias was determined by two external observers using the Cochrane checklists. After the search, the data provided in 51 documents was independently evaluated. Duplicate papers were excluded. Assessing the full texts of the remaining papers, 7 papers were approved. RESULTS: Pooled data of these seven studies revealed that the overall objective response rate was 68% (CI 64.1% to 72.1%; heterogeneity; I2 = 40.19%; p = 0.123) with partial remission (52%; CI 46.5% to 57.6%; heterogeneity; I2 = 28.36%; p = 0.212). In the pooled analysis, complete remission was 16.8 (CI 11.1% to 26.4%). Pooled data of six studies showed that stable disease was averaged to 19% (CI 16% to 23%; heterogeneity; I2 = 30%; p = 0.209; fixed-effect model). CONCLUSIONS: The results of the study indicate that nivolumab as a PD1 pathway inhibitor can be effective in treating relapsed and refractory cHL patients compared to other therapies, and lead to more effective treatment over the long term. Furthermore, the adverse effects of nivolumab are controllable and have a good safety profile.

Fludarabine and busulfan as a myeloablative conditioning regimen for allogeneic stem cell transplantation in high- and standard-risk leukemic patients.

Busulfan and cyclophosphamide (BuCy) are currently the most widely used myeloablative regimen to treat malignancies with allogeneic stem cell transplantation. Fludarabine has considerable efficacy in both immunosuppression and tumor cells killing with a minimal extramedullary toxicity. We evaluated the efficacy of 40 mg/m(2) fludarabine i.v. for 5 days and busulfan 4 mg/kg/day p.o. for 4 days as myeloablative conditioning regimen in 70 patients (median age 24 years) with acute leukemia or chronic phase of myelogenous leukemia. They all had human leukocyte antigen-matched sibling donors. The patients received 10 mug/kg granulocyte colony stimulating factor (GCSF), 24 h after stem cell infusion until engraftment occurred. Graft-versus-host disease (GVHD) prophylaxis included 3 mg/kg cyclosporine-A i.v. from day -2 to +6 followed by 12 mg/kg p.o. until day +60. The median time of neutrophil recovery (>0.5 x 109/l) and platelet recovery (>20 x 109/l) were 10 and 12 days, respectively. Mucositis (93%) and hepatic toxicity (16%) resolved with conservative therapy. The incidence of acute GVHD grade I-II and III-IV were 38.6 and 15.7% respectively. Overall survival and disease-free survival were 71 and 64% respectively with 17 months median follow-up for surviving patients. We conclude that FluBu may be used as a substitute for BuCy with almost the same efficacy and with a lower transplant adverse effect but to increase anti-leukemic effects, especially in acute lymphoblastic leukemia patients, it needs some modifications.