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Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

《医学前沿（英文）》 2021年第15卷第1期页码 108-115 doi: 10.1007/s11684-019-0730-8

摘要： Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group ( =0.03 and =0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

关键词： post-transplantation cyclophosphamide allogeneic hematopoietic stem cell transplantation lymphoid malignancies

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Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

SUN Ledong, SUN Jing, ZENG Kang, MENG Fanyi, DIAO Youtao, XU Dan, HUANG Liang, ZHAO Jie, Liu Qifa

《医学前沿（英文）》 2008年第2卷第2期页码 191-194 doi: 10.1007/s11684-008-0036-8

摘要： The aim of this study is to explore the effectiveness of autologous peripheral hematopoietic stem-cell transplantation in the treatment of refractory pemphigus. A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities. The diagnosis of pemphigus was made on the basis of the clinical, histologic and immunofluorescence findings. The patient had shown resistance to conventional therapy with glucocorticoid and immunosuppressive agents. Two months before admission, he complained of hip joint pain. X-ray and CT scan revealed aseptic necrosis of the femoral head. Stem-cell mobilization was achieved by treatment with cyclophosphamide, granulocyte colony-stimulating factor (G-CSF) and rituximab. Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use. Immunoablation was accomplished by using cyclophosphamide (200 mg/kg; divided into 50 mg/kg on days -5, -4, -3, and -2), antithymocyte globulin (ATG; 10 mg/kg; divided into 2.5 mg/kg on days -6, -5, -4, and -3), and rituximab (1200 mg/d; divided into 600 mg/d on days 0 and 7). Autologous peripheral hematopoietic stem cell transplantation was followed by reconstitution of the immune system which was monitored by flow cytometry. The glucocorticoid was withdrawn immediately after transplantation. The pemphigus titer turned negative 6 weeks after transplantation and remained negative. The patient was in complete drug-free remission with no evidence of residual clinical or serological activity of pemphigus during 1 year of follow-up. The patient’s response suggests that autologous peripheral hematopoietic stem cell transplantation may be a potential “cure” for refractory pemphigus. However, further studies are needed to evaluate the risk-benefit ratio of this approach in patients with pemphigus showing resistance to conventional therapy.

关键词： serological activity leukapheresis peripheral hematopoietic cyclophosphamide resistance