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Control study of melphalan instead of cyclophosphamide as a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation for treatment of myeloid malignancies

目的 评价以马法兰(Mel)替代改良白消安(Bu)＋环磷酰胺(Cy)(Bu/Cy)方案中Cy的预处理方案在异基因造血干细胞移植(allo-HSCT)治疗恶性髓系血液病中的有效性及安全性。 方法 分析94例进行allo-HSCT的恶性髓系血液病患者临床资料，其中48例采用Bu+Cy＋氟达拉滨(Flu)＋阿糖胞苷(Ara-C)(BCFA)方案预处理，46例采用Bu+Mel+Flu+ Ara-C (BMFA)方案预处理。移植后观察比较两组预处理方案相关不良反应、植入率、移植物抗宿主病(GVHD)、感染发生、非复发死亡(NRM)率以及总生存(OS)率。 结果 两组患者均获得中性粒细胞成功植入。BMFA组Ⅲ~Ⅳ度口腔溃疡以及腹泻发生率均高于BCFA组(P<0.05)，BMFA组急性GVHD(aGVHD)发生率较高，但差异无统计学意义(36.5％对56.5%，P=0.100)。中位随访42个月，BCFA组和BMFA组NRM率分别为12.5％和19.6% (P=0.400)。BMFA组复发率显著低于BCFA组，分别为4.3％和25.0%(P=0.009)。两组OS率分别为(71.8±6.7)％和(76.1±6.3)%(P=0.852)，无病生存(DFS)率分别为(67.8±8.9)％和(76.1±6.3)%(P=0.567)，BCFA组均略低于BMFA组，但差异均无统计学意义。 结论 应用Mel替代Cy的预处理方案治疗恶性髓系血液病复发率较低，并获得较满意的DFS率，但应注意预处理相关毒性的预防及aGVHD的治疗和干预。OBJECTIVE To evaluate melphalan instead of cyclophosphamide in modified busulfancyclophosphamide regimen as a new myeloablative conditioning regimen for the treatment of myeloid malignancies patients receiving allogeneic hematopoietic stem cell transplantation （HSCT）. METHODS The clinic data of 94 myeloid malignancies patients undergoing allogeneic HSCT were analyzed, of which 48 patients received Bu+Cy+Flu+Ara-C, 46 cases Bu+Mel+Flu+Ara-C regimens. Rregimen-related toxicity, engraftment, graft- versus-host disease（GVHD）, infection condition, non- relapse mortality, and overall survival were compared between the two groups. RESULTS All patients achieved neutrophil engraftment. The incidence of grade Ⅲ-Ⅳ oral mucositis and diarrhea in BMFA group was higher than in BCFA group（P<0.05）. The incidence of acute GVHD in BMFA group was also higher than in BCFA group but without statistically significant difference（36.5% over 56.5%, P=0.100）. With a median follow up of 42 months, the incidence of no relapse mortality in BCFA group was 12.5% and 19.6% in BMFA group（P=0.400）. The relapse rate in BMFA group（4.3%）was significantly lower than in BCFA group （25.0%, P=0.009）. The overall survival rates were（71.8±6.7）% and（76.1±6.3）%（P=0.852）, and diseasefree survival rates were（67.8±8.9）% and（76.1±6.3）%（P=0.567）were comparable between BCFA group and BMFA group. CONCLUSION Melphalan instead of cyclophosphamide as a new myeloablative conditioning regimen had lower relapse and satisfied disease-free survival rates, but the risk of regimenrelated toxicity and GVHD should be taken into consideration.

Comparison of outcomes of adult acute lymphoblastic leukemia patients underwent autologous and allogeneic hematopoietic stem cell transplantation

目的 对比分析成人急性淋巴细胞白血病(ALL)自体造血干细胞移植(auto-HSCT)和异基因造血干细胞移植(allo-HSCT)疗效差异。 方法 研究纳入2007年1月至2010年12月进行造血干细胞移植(HSCT)的106例成人ALL患者，其中auto-HSCT 50例，首次完全缓解(CR1)46例，第2次CR(CR2)4例，高危组21例，移植前检测微小残留病(MRD)均阴性；allo-HSCT患者56例，CR151例，CR25例，高危组44例，移植前14例MRD阳性。 结果 106例患者移植后中位随访22.9(0.8~63.3)个月，29例血液学复发。其中auto-HSCT、allo-HSCT患者3年累积复发率(RR)分别为(29.9±8.0)%和（32.7±6.8）%（P=0.402）。标危组患者auto-HSCT和allo-HSCT后RR差异无统计学意义（P=0.554），高危组患者auto-HSCT和allo-HSCT后RR差异亦无统计学意义（P=0.967）。allo-HSCT患者2年累积非复发死亡率(NRM)[(22.3±6.0)%]显著高于auto-HSCT患者(0)(P=0.001)。标危组患者auto-HSCT和allo-HSCT后3年总生存(OS)率分别为（77.1±13.2）%和(90.9±8.7)%（P=0.739）。高危组患者auto-HSCT和allo-HSCT后3年OS率分别为（68.7±10.8）%和(45.2±8.5)%(P=0.094)。 结论 成人ALL患者auto-HSCT和allo-HSCT同样有效，如果患者MRD持续阴性，auto-HSCT可成为allo-HSCT的有效替代治疗手段。OBJECTIVE To compare the outcomes of adult patients with acute lymphoblastic leukemia (ALL) who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS From Jan 2007 to Dec 2010, 106 adult ALL patients were retrospectively divided into two groups, 50 in auto-HSCT group and 56 in allo-HSCT group. Auto-HSCT group included 21 patients with high-risk, 46 patients in CR1 and 4 cases in CR2. All the 50 patients had negative minimal residual disease (MRD) prior to HSCT. Allo-HSCT group included 44 patients with high risk, 51 patients in CR1 and 5 cases in CR2, 15 patients with positive MRD before allo-HSCT. response, regulatory T cells (Treg), cytokines levels and treatment-related adverse effects were observed. RESULTS Of the total 106 patients, 29 patients relapsed at a medium follow-up of 22.9(0.8-63.3) months. The 3-year cumulative relapse rate (RR) was (29.9±8.0) % in auto-HSCT group and (32.7±6.8) % in allo-HSCT group. There were no significant differences in RR and overall survival (OS) between auto-HSCT and allo-HSCT groups, even of stratified risk groups. In standard risk group, 3-year OS was (77.1±13.2) % in auto-HSCT group and (90.9±8.7) % in allo-HSCT group (P=0.739). In high-risk group, 3-year OS was (68.7±10.8) % after auto-HSCT and (45.2±8.5) % after allo-HSCT (P=0.094). CONCLUSION Due to acceptable RR and OS, adult ALL patients with no MRD before HSCT showed favorable survival. Auto-HSCT may be a considerable choice for adult ALL patients with negative MRD when lacking of donors for allo-HSCT.

[Treatment of adult acute lymphoblastie leukemia with eosinophilia and abnormality of PDGFRA by autologous hematopoietic stem cell transplantation and imatinib: one case report and literatures review].

DOI:10.3760/cma.j.issn.0253-2727.2015.10.013 基金项目:天津市应用基础与前沿技术研究计划(14JCZDJC33000);国家科技支撑项目(2013BAIO1BO9) 作者单位:300020 天津,中国医学科学院、北京协和医学院血 液学研究所、血液病医院 通信作者:冯四洲,Email:sizhoufeng@medmail.com.cn Treatment of adult acute lymphoblastie leukemia with eosinophilia and abnormality of PDGFRA by autologous hematopoietic stem cell transplantation and imatinib: one case report and literatures review Shi Yuanyuan, Yang Donglin, Liu Qingzhen, He Yi, Zhang Rongli, Han Mingzhe, Feng Sizhou Corresponding author: Feng Sizhou, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. Email: sizhoufeng@medmail.com.cn

[IL-18 single nucleotide polymorphisms in hematologic malignancies with HLA matched sibling donor allogeneic hematopoietic stem cell transplantation].

OBJECTIVE To explore the impact of interleukin-18 (IL-18) single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation (allo-HSCT). METHODS Single- nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis (PCR-SSP) in 93 recipients and their HLA matched sibling donors. Hematopoietic reconstitution, incidences of graft versus host disease (GVHD) and infections, transplant related mortality (TRM), and disease free survival (DFS) were analyzed. RESULTS In comparison with -137 G/C+C/C donor genotype, patients with -137 G/G donor genotype had shorter duration of neutrophil recovery [15(11-23) days vs 17(11-24) days, P=0.01], higher incidence of extensive chronic GVHD (20.6% vs 3.3%, P=0.029), but no difference in the interval of platelet recovery [20(11-46) days vs 20(7-38) days, P=0.844]. The incidence of extensive chronic GVHD in -607 C/C donor genotype (31.6%) was significantly higher than that (10.8%) in C/A + A/A donor genotype (P=0.024). Recipients with -607 C/C genotype also had higher incidence (33.3%) of extensive chronic GVHD than those with C/A+A/A genotype (10.7%, P=0.016). There were no differences in acute GVHD, TRM, and DFS between different genotypes. CONCLUSION IL-18 -137 G homozygous genotype in donor facilitated neutrophil reconstitution, but increased the risk of extensive chronic GVHD in patients with allo-HSCT.

Outcome analysis of alternative donor allogeneic hematopoietic cell transplantation in the treatment of 19 severe aplastic anemia patients

OBJECTIVE To evaluate the efficacy of alternative donor allogeneic hematopoietic stem cell transplantation (AD allo-HSCT) in the treatment of severe aplastic anemia (SAA). METHODS Retrospective analysis of the clinical data of 19 SAA patients received AD allo-HSCT from May 2003 to December 2012. Of them, 12 received haploidentical HSCT (haplo-HSCT), 7 received unrelated donor transplantation. The conditioning regimen was CY+ATG+Flu±Ara-C±Bu/Mel, the GVHD preventing regimen was MMF+MTX+CSA/FK506; the median reinfusion quantity of CD34+ was 3.10(2.11-4.38)×10⁶/kg in allo-BMT and 4.90(2.08-6.88)×10⁶/kg in allo-PBSCT. RESULTS Hematopoiesis reconstitution was achieved in all 19 patients. Twelve patients developed acute graft-versus-host disease (aGVHD), and 7 developed chronic GVHD (cGVHD). Graft rejection (GR) was occurred in one patient. The median follow-up time was 13(3-115) months. Thirteen patients survived, and the prospective 5-year overall survival rate is (67.5±11.0)%. CONCLUSION AD allo-HSCT can be used as an alternative therapy for SAA patients without HLA matched sibling donor.

[Prophylaxis of invasive fungal infection with different administration regimens of itraconazole in patients with acute myeloid leukemia: a report from a randomized, controlled trial].

OBJECTIVE To evaluate the efficacy and safety of antifungal prophylaxis of itraconazole in patients with acute myeloid leukemia (AML) to probe the relationship of the antifungal effect and the adverse events with serum concentration. METHODS From April 2009 to May 2011, a total of 310 courses from 112 patients referred to our institute were enrolled in this study; of them, 297 courses were eligible for analysis. Eligible cases were randomized into oral group and injection/oral group according to different chemotherapy of induction and consolidation. Blood samples were collected at different time points for measurements of serum itraconazole levels. The morbidity of IFI and the adverse events were analyzed. RESULTS The morbidities of IFI in injection/oral and oral groups were 10.1% and 20.9%, respectively (P=0.010). 7 and 9 cases in injection/oral and oral groups, respectively were withdrawn from the study because of adverse events, and the difference between these two groups was of no significance. Serum itraconazole levels of injection/oral and oral groups were 672(299-1097) μg/L and 534(210-936) μg/L, respectively (P<0.01). CONCLUSION Antifungal prophylaxis with itraconazole in AML patients was effective and safe. Prophylactic effect with injection/oral itraconazole was superior to oral itraconazole solution; moreover, prophylactic effect of itraconazole was highly correlated with its serum level.