A Comparison of Dexamethasone Plus Vincristine versus Standard Regimen in Induction Therapy of Adult Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplantation.

Background: Current treatment options of acute lymphoblastic leukemia(ALL) include chemotherapy alone or hematopoietic stem cell transplantation (HSCT) following induction chemotherapy both along with CNS prophylaxis. The usual and standard induction regimens currently administered could have severe complications and mortality. Materials and Methods: To lessen induction regimen complications in ALL patients who undergo HSCT, we used a cytoreduction induction regimen including dexamethasone (8 mg, IV, three times a day, for 28 days) and vincristine(1.4 mg/m2, IV, on days 1,8,15 and 22) for 49 newly diagnosed adult ALL patients followed by an early sibling donor HSCT within two months. The results were matched with outcomes of HSCT in 172 ALL patients inducted by standard induction regimen. Results: Median follow-up time was 5.41 years in the standard group and 5.27 years in the other. All patients of the case group (100%) achieved complete remission. Landmark analyses were performed to scrutinize the effect of treatments on different time intervals: first two years and 2nd to end years. Type of treatment had no significant effect on the hazard of death in the first landmark (HR=0.87, P=0.64). Cytoreduction regimen amplified the hazard of death 3.43 times more than the standard regimen in the second landmark (HR=3.43 P=0.035). Multivariate analysis showed that the cytoreduction regimen reduced the hazard of relapse about 22%, but not statistically significant (HR=0.78, P-value=0.24). Conclusion: Overall, it seems despite achieving complete remission in induction therapy, depth of response is a critical predictor for long-term outcomes of HSCT in ALL patients, and the use of multiple agents may be necessary to decrease tumor cell burden and minimal residual disease(MRD).

Gibbon ape leukemia virus transduction of peripheral blood CD34+-derived dendritic cells.

BACKGROUND: Dendritic cells (DCs) play a critical role in the immune response and are a candidate for immunotherapy in cancer. Since gibbon ape leukemia virus (GALV) transduction of CD34+ cells is reasonably efficacious, we assessed the efficacy of GALV transduction of CD34+ derived DCs as a possible approach to creating genetically modified DCs for immunotherapy. METHODS: Peripheral blood CD34+ cells were transduced with retroviruses obtained from the PG13/LN C8 cell line, with the neomycin gene as a marker gene. After prestimulation of hematopoietic cells for 24 hours with 10 ng/mL interleukin (IL)-3, 10 ng/mL IL-6, 100 ng/mL stem cell factor, 100 ng/mL granulocyte-macrophage colony stimulating factor and 8 Amicrog/mL protamine sulfate, the cells were cultured in a transforming media prior to differentiating into DCs by GM-CSF, TNF-a and IL-4. Immunophenotyping analyses for confirmation of the generated DCs, colony formation assay and PCR were done for the expression of neomycin gene in the transduced cells. RESULTS: Titration of viral vectors indicated a transduction efficiency of 1×10(5) CFU/mL. Transduction efficiency for the CD34+ cells transformed to DCs was 45% and 38% before and after DC differentiation, respectively. Additionally, a mean (SEM) of 26.9% (11.4%) and 41.4% (11.8%) of the genetically modified DCs were positive for CD86+ HLA-DR and CD1a+CD14, respectively CONCLUSION: This study showed that the majority of transduced CD34+ cells were successfully differentiated into cells identical to DCs according to morphology and immunophenotyping features, which could be a potential application in immunotherapy.

Effects of chimerism on graft-versus-host disease, disease recurrence, and survival after HLA-identical marrow transplantation in Iran.

BACKGROUND: The coexistence of recipient's and donor's hematopoietic systems after allogeneic marrow transplantation is called mixed chimerism. OBJECTIVE: The objective of this study was to evaluate the effects of MC on graft-versus-host disease (GVHD), disease recurrence, and survival after HLA identical marrow transplantation in a transplant center in Iran. METHODS: The association of MC with acute GVHD, disease recurrence, survival, and relapse-free survival was investigated in 91 patients who underwent either bone (n = 12) or peripheral blood (n = 79) HLA-identical marrow transplantation. Chimerism was assessed using multiplex amplification of short tandem repeats (STR). Patients had thalassemia (n = 19), acute myelogenous leukemia (AML) (n = 29), acute lymphocytic leukemia (ALL) (n = 20), chronic myelogenous leukemia (CML) (n = 18), and other diseases (n = 5). The median age was 21 (range: 3 - 50) years. There were 38 (42%) female and 53 (58%) male participants. Conditioning was made through busulfan plus cyclophosphamide in 34 patients; busulfan plus fludarabin in 51 patients; and busulfan plus fludarabin plus antithymocyte globulin in 6 patients. The median follow-up was 13 months. RESULTS: On day +30, complete chimerism (CC) was observed in 72 (79%) patients, MC in 15 (17%), and no chimerism in 4 patients. The incidence of acute GVHD was significantly (P = 0.01) lower in mixed chimeras than in complete chimeras. There was no significant difference in acute GVHD grade (I, II vs. III, IV) between the two groups. The incidence of relapse was 18%. There was no difference in relapse rate between MC and CC groups. Overall survival was 89%. There was no significant difference in the overall survival between MC and CC group (96% vs. 85%, respectively). Relapse-free survival was 80% that was not significantly different between the two groups. CONCLUSION: Despite some previous reports, we found no significant difference in the survival and relapse rates between MC and CC groups.