High incidence of Pneumocystis jirovecii pneumonia in allogeneic hematopoietic cell transplant recipients in the modern era.


  • 影响因子:3.53
  • DOI:10.1016/j.jcyt.2019.11.002
  • 作者列表:"Evernden C","Dowhan M","Dabas R","Chaudhry A","Kalra A","Dharmani-Khan P","Gregson D","Johnson A","Jupp J","Jimenez-Zepeda V","Jamani K","Duggan P","Tay J","Khan F","Daly A","Storek J
  • 发表时间:2020-01-01

BACKGROUND:International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic hematopoietic cell transplantation, and longer in patients with graft-versus-host disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG) for GVHD prophylaxis. METHODS:We performed a retrospective chart review of 649 patients, all of whom received ATG as part of GVHD prophylaxis. RESULTS:The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207 and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with inhaled pentamidine. DISCUSSION:In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL or if there is a high incidence of PJP in the community. For patients with GVHD receiving ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled pentamidine.


背景: 国际肺孢子菌肺炎 (PJP) 预防指南建议异基因造血细胞移植后预防时间 ≥ 6个月,移植物抗宿主病 (GVHD) 或免疫抑制治疗 (IST) 患者预防时间更长。这些建议基于未常规接受抗胸腺细胞球蛋白 (ATG) 预防GVHD的患者队列。 方法: 我们对649例患者进行了回顾性图表回顾,所有患者都接受了ATG作为GVHD预防的一部分。 结果: 3年和5年时,明确PJP的累积发生率均为3.52% (中位随访时间,存活者为1648天)。在207至508天之间,13例非GVHD患者发生了PJP,部分原因是低CD4 T细胞计数 (<200 CD4 T细胞/μ l)。在389至792天之间,8名GVHD患者发生了PJP,部分原因是不遵守PJP预防指南 (在停止IST后 <3个月停止PJP预防)。在接受复方新诺明、氨苯砜或阿托伐奎酮预防治疗的患者中,未观察到突破性PJP感染,而吸入五脒组中观察到3例。 讨论: 总之,对于接受含ATG的GVHD预防的非GVHD患者,6个月的PJP预防是不够的,特别是如果CD4 + T细胞计数 <200个细胞/μ l或社区中PJP的发病率高。对于接受含ATG的GVHD预防的GVHD患者,继续PJP预防直至IST停药后 ≥ 3个月是重要的。优选复方新诺明、氨苯砜和阿托伐喹,而非吸入性戊脒。



来源期刊:Congenital anomalies
作者列表:["Shahid M","Firasat S","Satti HS","Satti TM","Ghafoor T","Sharif I","Afshan K"]

METHODS::Fanconi anemia (FA) is a recessive disorder that predispose to bone marrow failure and multiple congenital anomalies in affected individuals worldwide. To date, 22 FA genes are known to harbor sequence variations in disease phenotype. Among these, mutations in the FANCA gene are associated with 60% to 70% of FA cases. The aim of the present study was to screen FA cases belonging to consanguineous Pakistani families for selected exons of FANCA gene which are known mutational hotspots for Asian populations. Blood samples were collected from 20 FA cases and 20 controls. RNA was extracted and cDNA was synthesized from blood samples of cases. DNA was extracted from blood samples of cases and ethnically matched healthy controls. Sanger's sequencing of the nine selected exons of FANCA gene in FA cases revealed 19 genetic alterations of which 15 were single nucleotide variants, three were insertions and one was microdeletion. Of the total 19 sequence changes, 13 were novel and six were previously reported. All identified variants were evaluated by computational programs including SIFT, PolyPhen-2 and Mutation taster. Seven out of 20 analyzed patients were carrying homozygous novel sequence variations, predicted to be associated with FA. These disease associated novel variants were not detected in ethnically matched controls and depict genetic heterogeneity of disease.

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作者列表:["Szanto T","Nummi V","Jouppila A","Brinkman HJM","Lassila R"]

METHODS::In type 3 von Willebrand disease (VWD3), the most severe form with absent von Willebrand factor (VWF), the bleeding phenotype is variable. Platelet contribution to the hemostatic defect in VWD3 calls upon further studies. We investigated the contribution of platelets to in vitro thrombin generation (TG) and platelet procoagulant activity in VWD3. TG was assessed by calibrated automated thrombogram (CAT) in platelet-poor (PPP) and -rich plasma (PRP) from 9 patients before and in 6 patients also 30 min after receiving their regular VWF therapy. Responsiveness of PPP to FVIII and protein S was also investigated. TG data were compared with routine laboratory variables, rotational thromboelastometry (ROTEM) and platelet expression of P-selectin and phosphatidylserine in flow cytometry. Compared with healthy controls, TG was markedly decreased in VWD3 PPP (peak thrombin was 16% of normal median), but not in PRP (77% of normal median) (p = 0.002). Six out of nine patients (67%) were high responders in their platelet P-selectin, and 5/9 (56%) in phosphatidylserine expression. Replacement therapy improved TG in PPP, while in PRP TG only modestly increased or was unaffected. In PPP, FVIII levels associated with TG and in vitro FVIII-supplemented TG inclined up to threefold. Conversely, a FVIII inhibitory antibody reduced plasma TG in all, but especially in patients with remnant FVIII levels. Inhibition of protein S improved plasma TG, particularly at low FVIII levels. ROTEM failed to detect VWD3.In VWD3, TG is reduced in PPP and regulated by FVIII and protein S, but TG is close to normal in PRP. VWD3 platelets seem to compensate for the FVIII-associated reduction in TG by their exposure of P-selectin and phosphatidylserine.

作者列表:["Al-Momani D","Al-Qasem W","Kasht R","Sultan I"]

METHODS:BACKGROUND:The optimal timing of initiating granulocyte-colony stimulating factor following chemotherapy in pediatric patients has not been clearly defined. This study aimed to compare the administration of granulocyte-colony stimulating factor on day 1 versus day 3 postchemotherapy in pediatric patients with Ewing sarcoma. METHOD:A retrospective study of pediatric patients with Ewing sarcoma who received granulocyte-colony stimulating factor following chemotherapy between January 2016 and September 2018 at a comprehensive cancer center. The institution's chemotherapy protocol for Ewing sarcoma was modified in April 2017 to include granulocyte-colony stimulating factor initiation on day 3 instead of day 1 post-chemotherapy. Febrile neutropenia requiring hospitalization, duration of hospital stay, and chemotherapy delay were compared for patients before and after the protocol change. RESULTS:Over the study period, 250 cycles were evaluated with day 1 granulocyte-colony stimulating factor and 221 cycles with day 3 granulocyte-colony stimulating factor. There were no differences between the day 1 and day 3 groups in the number of cycles associated with Febrile neutropenia requiring hospitalization (34 vs. 19, p = 0.086), and the length of Febrile neutropenia-related hospitalization (mean 4 ± 2.1 vs. 4.6 ± 1.8, p = 0.123). However, delay in chemotherapy due to neutropenia was reported in significantly more cycles in the day 1 group, compared to the day 3 group (37 vs. 16, p = 0.01). CONCLUSIONS:Febrile neutropenia resulting in hospital admission and the length of hospital stay was not different between pediatric patients with Ewing sarcoma who received granulocyte-colony stimulating factor on day 1 or day 3 post-chemotherapy. Chemotherapy delay due to neutropenia was higher in patients who received granulocyte-colony stimulating factor on day 1. Larger studies are required to fully determine the impact of delayed initiation of granulocyte-colony stimulating factor.

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