Key Points• A salvage therapy for adults with refractory hemophagocytic lymphohistiocytosis.• Liposomal doxorubicin treatment combined with etoposide and methylprednisolone showed an encouraging overall response and was welltolerated.Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death. Although standard therapy has dramatically improved survival in HLH patients, approximately 30%, especially adults, show no response to current treatment strategies. This prospective study aimed to investigate the efficacy of liposomal doxorubicin treatment combined with etoposide and methylprednisolone (doxorubicin-etoposidemethylprednisolone; DEP) as a salvage therapy for adult refractory HLH. Adult patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy were enrolled in this study between June 2013 and June 2014. Response to salvage therapy was assessed at 2 and 4 weeks after initiation of DEP therapy and patients were followed until death or until November 2014. Sixty-three refractory HLH patients were enrolled, including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus-associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown underlying diseases. Seventeen cases (27.0%) achieved complete response and 31 cases (49.2%) achieved partial response. The overall response was 76.2% (48/63). Patients who showed no response to DEP died within 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved partial or complete response survived to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or splenectomy. Our study suggests that DEP regimen is an effective salvage regimen for adult refractory HLH, which can prolong patient survival as we continue to understand the responsible mechanisms and bridge the gap between HLH and its underlying diseases. This study was registered in the Chinese Clinical Trials Registry Platform
A convenient method for the synthesis of polyamides containing N-methylpyrrole (Py) and N-methylimidazole (Im) in solution has been developed. Most of the building blocks have been prepared by a haloform reaction in a simple way that column chromatography can be avoided. By use of the DCC/HOBT coupling reaction, the building blocks prepared have been effectively connected to construct a variety of subchains and polyamides without employing amino protection and deprotection. By use of the present method, an eight-ring polyamide, PyPyPyPygammaPyImImPybetaDp (gamma is gamma-aminobutyric acid, beta is beta-alanine, Dp is N, N-dimethylpropyldiamine), has been synthesized by the coupling of two four-ring subchains in one step.
Myeloablative conditioning-based allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the treatment of adult and adolescent hemophagocytic lymphohistiocytosis (HLH) is rarely reported. We conducted a retrospective study of 30 adult and adolescent HLH transplanted for primary HLH (n = 4), tumor-HLH (n = 8), EBV-HLH (n = 14), and underlying disease-unknown (UDU)-HLH (n = 4). Peripheral blood stem cells (PBSCs) were the stem-cell source in all patients. Twenty-three patients were transplanted from HLA-haploidentical family donors, six from HLA-identical sibling donors, and one from a matched unrelated donor. Four patients appeared with mixed chimerism (MC), and no patient presented with graft failure. There was a high risk for EBV reactivation with an incidence of 47 %. Two patients developed post-transplant lymphoproliferative disorder (PTLD) and three were considered primary disease recurrent. With a median follow-up of 26 months, 19 patients survived and 11 patients died. The estimated 2-year overall survival (OS) was 63.3 ± 8.8 % in all patients, 100 % in primary HLH, 64.3 ± 12.8 % in EBV-HLH, 50.0 ± 17.7 % in tumor-HLH, and 50.0 ± 25.0 % in UDU-HLH. Myeloablative conditioning-based allo-HSCT is an effective treatment for adult and adolescent HLH to achieve complete remission and long-term survival.
Our findings expanded the understanding of the role of BATF2 in tumors, and also suggested a potential of using BATF2 as a therapeutic target to hinder bevacizumab induced EMT in glioblastoma.
Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. Current standard therapy increased the complete remission (CR) rate to more than 50%. Even so, about 30% patients fail the standard treatment. This study aimed to investigate the efficacy of liposomal doxorubicin together with etoposide, and high dose methylprednisolone (DEP) as a salvage therapy for adult refractory HLH.
Methods: Refractory HLH was defined as patient who did not achieve at least partial remission (PR) 2 weeks after initial standard HLH therapy. The DEP regimen included liposomal doxorubicin 25mg/m2 d1, etoposide 100mg/m2 Qw and methylprednisolone 15mg/kg d1-3, 2mg/kg d4-6, 1mg/kg d7-10,0.75mg/kg d11-14. We estimated the curative effect after 2 weeks therapy and 4 weeks therapy.
Results: We observed 63 refractory HLH patients from Jun 2013 to Jun 2014, including 42 males and 21 females. All the data were gathered from Beijing Friendship Hospital, 307 Hospital of PLA, Peking University People’s Hospital, Peking University Third Hospital, Beijing Chao-Yang Hospital, and Navy General Hospital. The median age was 34 years old (Range 18-78). Seventeen patients (27.0%) achieved CR and 31 patients (49.2%) achieved PR. The overall response reached 76.2% (48/63). The underlying disease of HLH were diagnosed within 2 to 8 weeks after HLH diagnosis, including 29 cases of lymphoma associated HLH, 22 cases of EBV associated HLH and 4 cases of familial HLH. There were still 8 cases had unknown underlying disease. The patients who had no response to DEP were died within 2 to 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved PR or CR survived to undergo subsequent chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HCT) or splenectomy. There were significant improvements on leukocytes, ferritin and soluble CD25 (sCD25) after 2 weeks therapy. Thrombocytes and glutamic-pyruvic transaminase (GPT) had improvements after 4 weeks therapy.
Conclusion: DEP regimen appears to be an effective salvage protocol for refractory HLH. Prospective randomized controlled trials of DEP regimen will further estimated the curative effect and define optimal dosing levels and schedules.
Disclosures
No relevant conflicts of interest to declare.
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