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Blood and marrow transplantation (BMT) is rarely available in many low- to middle-income countries (LMICs). In 2012, Civil Service Hospital, a government hospital in Kathmandu, partnered with the University of Illinois at Chicago to consult on the establishment of BMT in their hospital, train staff, and promote educational activities. The implementation of BMT occurred in 3 phases over 4 years and included regular onsite visits, training of personnel in Chicago, continuous remote communication, and co-organization of educational events in Kathmandu. The Nepalese government funded the construction of a state-of-the art BMT unit and stem cell laboratory inside Civil Hospital. Autologous (auto) hematopoietic stem cell transplantation (HSCT) was started in 2016, and allogeneic (allo) HSCT from matched related donors (MRDs) or haploidentical (haplo) donors was initiated in 2017. The cost of transplantation was $5200 for auto-HSCT, $10,000 for MRD HSCT, and $13,300 for haplo HSCT. The major socioeconomic determinants reported by Nepalese BMT providers were the cost of transplantation, loss of revenue of the patient and/or caregiver, and cost of transportation. All patients (n = 66) received peripheral blood stem cell grafts, and all allo-HSCT recipients were given post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis. Among recipients of auto-HSCT (n = 30), with a median follow-up of 1029 days (range, 130 to 1653 days), 87% were alive, and transplantation-related mortality (TRM) was 10%. Among allo-HSCT recipients (n = 36), all patients engrafted, and at a median follow-up of 204 days (range, 12 to 1131 days), 75% of them were alive (MRD, 71%; haplo, 83%), with a TRM of 19%. Only 3 of 36 patients developed acute GVHD grade II-IV. The median overall survival in auto-HSCT recipients was 1610 days and was not reached in allo-HSCT recipients. The long-lasting partnership with University of Illinois at Chicago helped build capacity and allowed the Civil Service Hospital team to establish a BMT program in Nepal that has high quality standards at an affordable cost for the majority of patients.

Purpose Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare form of extranodal DLBCL. In this study, we aimed to determine the patterns of relapse and the optimal treatment strategy for PB-DLBCL in the rituximab era. Methods We retrospectively collected data from Chinese Southwest Oncology Group-affiliated institutes. Patients diagnosed with PB-DLBCL from 2008 to 2019 and treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or R-CHOP-like regimens were included. Results A total of 135 PB-DLBCL patients treated with R-CHOP or R-CHOP-like regimens were eligible for this study. With a median follow-up of 43 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 84.7% and 69.6%, respectively. Continuous treatment failure was observed, especially affecting the breast and central nervous system (CNS). Consolidative RT significantly reduced the risk of breast relapse (p = 0.013). Relapse in CNS were detected in 13 (9.6%) patients, of whom 4 had received intrathecal prophylaxis and 9 had not received CNS prophylaxis. None of the patients who received high-dose methotrexate (HD-MTX) had CNS relapse. CNS relapse risk was reduced by HD-MTX (p = 0.036). Furthermore, we screened the genetic mutation profile of PB-DLBCL and found that MYD88 and/or CD79B mutations were present in all patients with CNS relapse, whereas patients with MYD88 and/or CD79B mutations who received HD-MTX did not experience CNS relapse. Conclusions Our results indicate that consolidative RT decreased the risk of breast relapse. Prophylactic HD-MTX reduced the risk of CNS relapse, especially in patients with MYD88/CD79B mutations.

To investigate the apoptosis-inducing effect of peroxisome proliferator-activated receptor γ (PPARγ) agonist ciglitazone (CGZ) on leukemic HL-60 cells and its mechanisms of action.HL-60 cells in vitro culture medium were subject to different concentrations of CGZ (10-50 µmol/L) for 24, 48 and 72 h. MTT assay was used to detect the cell inhibitory rate and agarose gel electrophoresis to observe DNA fragmentation. Flow cytometry (FCM) and Annexin V/PI staining were used to detect CGZ and/or GW9662 (PPARγ antagonist)-induced cell apoptosis. The expression of PPARγ was examined by RT-PCR and Western blotting. The caspase-3 and protein levels in mitogen-activated protein kinase signaling pathways (MAPKs, p-P38, p-ERK and p-JNK) were also detected.CGZ (over 30 µmol/L) could inhibit the growth of HL-60 cells in both time- and dose-dependent manner. After treatment for 72 h, the cell growth inhibitory rate in 50 µmol/L CGZ (84% ± 11%) treated cells was found more higher than that in both 40 µmol/L and 30 µmol/L CGZ treated cells (72% ± 13%, 59% ± 13%, P0.01) and a typical DNA ladder was also observed by agarose gel electrophoresis. The expression of PPARγ was gradually up-regulated by CGZ treatment and could be down-regulated partially by PPARγ antagonist GW9662. The results also revealed that CGZ-induced cell apoptosis (49.7%, 72 h) could not be inhibited thoroughly by GW9662 (36.2%, control:3.2%). It indicated that the CGZ-induced cell apoptosis was partially PPARγ-independent. Western blotting showed a cleavage of caspase-3 zymogen protein and up-regulation of p-P38 protein. Thus it indicated that the activations of caspase-3 and P38 MAPK were involved in CGZ-induced cell apoptosis.CGZ inhibits cell growth by induction of cell apoptosis in HL-60 cells via PPARγ dependent and independent signaling pathways. The activations of caspase-3 and P38 MAPK may be one of the important mechanisms in CGZ in treated HL-60 cells.

e19508 Background: Ritubximab (RTX) with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) regimen is a gold standard therapy in treatment of diffuse large B-cell lymphoma (DLBCL)...