Mycophenolate mofetil use after unrelated hematopoietic stem cell transplantation for prophylaxis and treatment of graft‐vs.‐host disease in adult patients in Japan

Our previous study of 301 patients who received hematopoietic stem cell transplantation (HSCT) from related donors demonstrated the efficacy of mycophenolate mofetil (MMF) for prophylaxis and treatment of graft‐vs.‐host disease (GVHD). In this study, we investigated the safety and efficacy of MMF in 716 adult patients who received unrelated HSCT. The incidences of Grade II–IV and III–IV acute GVHD in the prophylactic administration group were 38.3% and 14.3%, respectively. These rates were not statistically significant when evaluating the MMF dosage and graft source. The incidences of limited and extensive chronic GVHD were 16.6% and 11.1%, respectively. In the therapeutic administration group, 69.1% of the subjective symptoms for both acute and chronic GVHD improved. With respect to the adverse events, 75 infections and 50 cases of diarrhea were observed, and the frequency of these events increased with increasing MMF dose. The overall survival rate was 36.4% after a median follow‐up period of three yr. This study shows that MMF is safe and effective for the prevention and treatment of GVHD in patients who have received HSCT from unrelated donors.     

Piperacillin‐tazobactam vs. imipenem‐cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia

This randomized, dual‐center study compared the efficacy and safety of piperacillin‐tazobactam (PTZ) and imipenem‐cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of 10 patients in the PTZ group and one of eight patients in the IMP group needed to switch the empiric antibiotic (p = 0.025). Compared with PTZ, IMP had more gastrointestinal adverse events (p = 0.045). This study demonstrates that IMP had better efficacy than PTZ as an empiric antibiotic for febrile neutropenia in the HSCT setting, but with more gastrointestinal side reactions.     

Micafungin as antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation: results of different dosage levels in clinical practice

Micafungin has been approved for the prophylaxis of Candida infections in patients undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Here, we report a single‐center experience of three different dose levels regarding efficacy, toxicity, and colonization with Candida ssp. in clinical practice. In total, 150 consecutive adult patients who underwent allo‐HSCT received micafungin at a dosage of 50, 100, or 150 mg once daily for primary antifungal prophylaxis. Of those patients receiving more than six d of micafungin prophylaxis, 12/46 (26%), 6/44 (14%), and 9/46 (20%) were switched to empiric antifungal treatment. The frequency of invasive fungal infections (IFIs) according to EORTC criteria did not differ significantly (7/46; 15% vs. 5/44; 11% vs. 5/46; 11%) across the different dosage groups. In the 50‐mg group, there was one case of candidemia with C. parapsilosis after 12 d of micafungin prophylaxis. In all three groups, micafungin prophylaxis was well tolerated without any case of toxicity‐related treatment discontinuation. Renal function was not significantly altered, while increase of bilirubin was mainly due to concomitant ATG application. The incidence of IFIs is similar irrespective of the micafungin dosage while there was a trend toward more frequent change to empiric antifungal treatment as well as oropharyngeal colonization with candida in the lowest dosage group.     

Timing of CMV‐specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation

The aim of this study was to characterize timing, kinetic, and magnitude of CMV‐specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV‐specific T‐cell response was measured in blood, while CMV viral load and chimerism were determined by real‐time PCR. Patients that reconstituted CMV‐specific T‐cell response within 6 weeks after Allo‐SCT showed a more robust immune response (CD8⁺: 0.7 cells/μl vs. 0.3/μl; P‐value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P‐value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P‐value = 0.04), and better overall survival (72%; CI: 0.53–0.96 vs. 42% CI: 0.24–0.71; P‐value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant‐related mortality than nonviremic patients after 1 year (33% CI: 0.15–0.52 vs. 0% CI: 0.05–0.34; P‐value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV‐positive serostatus (P‐value = 0.02) and acquiring CMV‐specific T‐cell response after 6 weeks post‐transplantation (P‐value = 0.009). In conclusion, timing of acquiring a positive CMV‐specific T‐cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.     

Comparative analysis of post‐transplant lymphoproliferative disorder after kidney transplantation versus hematopoietic stem cell transplantation

Post‐transplant lymphoproliferative disorder (PTLD) is a major complication caused by immune‐suppression after transplantation. Survival outcome is known to be poor and the characteristics are not fully understood because of its rare incidence. This single center retrospective study enrolled 41 adult PTLD patients after kidney‐transplantation (KT, n = 28) and hematopoietic stem cell transplantation (HSCT, n = 13) from 1992 to 2012. We compared the characteristics and estimated the survival outcomes according to several factors [age‐adjusted‐IPI (aaIPI), pathologic subtype, viral status, extranodal manifestation] and added some significant parameters to aaIPI scoring system. Post‐HSCT‐PTLD patients were younger and showed earlier onset, and viral status was more frequently identified. Ten‐year OS of the entire group was 44% but the 10‐year OS was not significantly different between post‐KT‐PTLD and post‐HSCT‐PTLD (39% vs. 56%, P = 0.860). The time onset of PTLD and viral statuses were not meaningful, however, aaIPI, age > 50, extranodal manifestation and monomorphic subtype were predictive for OS. We used those factors for PTLD‐specific scoring which showed intermediate‐risk (HR = 7.1, P = 0.019) and high‐risk (HR = 16.5, P = 0.001) presented worse OS compared to low‐risk subgroup. Although the treatment strategies were heterogenous, this study showed comprehensive PTLD data between KT versus HSCT, and our PTLD‐specific scoring might be validated by another larger studies.     

Universal perioperative antimicrobial prophylaxis is not necessary in kidney transplantation

Despite significant improvements in renal transplantation, certain basic issues remain unresolved such as the routine use of perioperative antimicrobial prophylaxis (AMP). To address the need for AMP, we retrospectively evaluated the clinical course of 442 consecutive renal transplant recipients (RTRs) who did not receive any AMP except for trimethoprim/sulfamethoxazole. Three hundred and forty RTRs received induction therapy with low-dose rabbit anti-thymocyte globulin, while the other 102 patients were treated with basiliximab. All RTRs received tacrolimus, mycophenolic acid, and prednisone. Nine patients (2%) developed surgical site infection (SSI). SSIs were more common in obese and older patients. All SSIs were superficial and responded well to wound drainage and outpatient antibiotic therapy. No patient or graft was lost owing to SSI. Our study shows that despite many predisposing factors, SSIs are rare following renal transplantation even in the absence of AMP. Therefore, to avoid the emergence of antibiotic-resistant pathogens, excessive costs, and antibiotic-related adverse events, we suggest that AMP should be used only in selected circumstances such as in recipients older than 65 yr or when the body mass index (BMI) is > 35.     

Stenotrophomonas maltophilia infection during allogeneic hematopoietic stem cell transplantation: a single‐center experience

To examine risk factors for Stenotrophomonas maltophilia (S. maltophilia) infection during allogeneic hematopoietic stem cell transplantation (allo‐HSCT), we retrospectively analyzed 259 patients who underwent allo‐HSCT. Not only S. maltophilia infection but also S. maltophilia colonization was associated with mortality during allo‐HSCT. Among 52 episodes in 39 patients in whom S. maltophilia was detected, documented infection developed in 33 episodes (25 patients). The onset of S. maltophilia infection in the period from the conditioning regimen to engraftment was associated with a high mortality rate. Breakthrough S. maltophilia infection developed in 24% of the patients during prophylactic administration of fluoroquinolones, to which S. maltophilia is sensitive. Reinsertion of a central venous catheter (CVC) immediately after removal was suggested to be a risk for persistent S. maltophilia infection in the period of neutropenia. Our results indicated that (i) onset of S. maltophilia infection in the period from the conditioning therapy to engraftment and (ii) removal and immediate reinsertion of a CVC as treatment after the onset of S. maltophilia infection are possible risk factors for S. maltophilia‐related mortality during allo‐HSCT.     

Ultrasonographic evaluation of gastrointestinal graft‐versus‐host disease after hematopoietic stem cell transplantation

Gastrointestinal graft‐versus‐host disease (GI‐GVHD) is a major and life‐threatening complication of hematopoietic stem cell transplantation (HSCT). This study evaluated the efficacy of ultrasonography (US) for assessing and monitoring GI‐GVHD. GI tract was evaluated by US in 81 patients. US findings were positive in 43 patients, including 11 false positive, and negative in 38 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of US for the diagnosis of GI‐GVHD were 100%, 78%, 74%, 100%, and 86%, respectively. Diffuse wall thickening of the ileum was the most frequent finding in patients with GI‐GVHD. Severity of GI‐GVHD was correlated with the thickness of internal low echoic layer of the wall, the echogenicity of mesenteric fat tissue, and the intensity of Doppler signaling. We classified US findings of GI‐GVHD into four US grades. There was a significant correlation between clinical stage of GI‐GVHD and the US grade. These ultrasonographic abnormalities were improved with clinical improvement of GI‐GVHD upon treatment. Thus, US is an effective and efficient non‐invasive means of identifying the extent and severity of GI‐GVHD and monitoring response to treatment.     

异基因造血干细胞移植后并发出血性膀胱炎的高危因素和防治措施

目的 评估改良的水化碱化方案对预防和治疗非亲缘异基因造血干细胞移植(URD-HSCT)后出血性膀胱炎(HC)的效果及安全性,探讨URD-HSCT后并发HC的危险因素.方法 151例血液系统恶性疾病患者接受了URD-HSCT,所有患者移植前均接受白消安+环磷酰胺(BuCy2)方案预处理.在使用环磷酰胺(Cy)过程中,所有患者均接受改良的水化碱化输液方案,分别在静脉滴注Cy后0、3、6、9、12 h分5次静脉注射美司钠,总量为Cy总量的120%～160%;于开始使用Cy时至结束后24 h(共计72 h)经中心静脉持续输液,输液量5000 ml·m-2·d-1,匀速输注,每500 ml液体中加入50 g/L碳酸氢钠20 ml,间断应用利尿剂,保持液体出入量平衡;每小时测尿pH值,保持尿pH值＞7.5.结果 URD-HSCT后共有26例患者发生HC,发生率为17.2%(26/151),中位发病时间为40d(8～89 d),无患者发生早发性HC.移植后26例HC患者再次接受改良的水化碱化尿液治疗,部分患者接受膀胱持续冲洗,所有患者均治愈,无患者因HC而死亡.经统计分析表明,以下因素与HC的发病明显相关:男性患者,相关系数(OR)值=3.093,95%可信区间(CI)为1.145～8.353,P＜0.05;急性GVHD,OR值=18.044,95%CI为3.952～82.392,P＜0.01;≥30岁,OR值=6.077,95%CI为1.585～23.299,P＜0.01.结论 改良的水化碱化方案是预防和治疗URD-HSCT后HC的安全有效的措施,尤其是由Cy预处理引起的早发性HC;男性患者、年龄≥30岁以及移植后并发急性GVHD是引起HC的危险因素.

Abstract：

Objective To investigate the efficacy and safety of the optimal alkalized hydration solution for hemorrhagic cystitis (HC) following unrelated donor allogeneic hematopoietic stem cell transplantation (URD-HSCT), and the risk factors and prophylaxis measures about HC.Methods The clinical data of 151 HC patients who underwent URD-HSCT were retrospectively analyzed. All patients were given busulfan/cyclophosphamide (BuCy)-based conditioning regimen.During Cy therapy, all patients were given the optimal alkalized hydration solution to prevent HC.MESNA was given intravenously after administration of Cy at 0, 3, 6, 9, 12 h, and its total dose was administration of Cy to 24 h under the ECG monitoring. Each 500 ml liquid contained 50 g/L sodium bicarbonate 20 ml. Urinary pH value was monitored every one hour (keeping urine pH＞7. 5). Results None of early onset HC occurred. Twenty-six of 151 (17. 2 %) patients developed late onset HC, and the median onset time was 40 (8～89) days after transplantation. During the therapy, no symptoms of the circulatory system, no congestive heart failure and no acid-base electrolyte imbalance occurred. All HC patients after re-hydration, diuretic, and (or) continuous bladder irrigation and other indwelling catheter after treatment, were cured. The statistical analysis showed that the following factors were significantly associated with HC: male (OR = 3. 093, 95 % CI, 1. 145～8.353, P＜0. 05), acute graft versus host disease (aGVHD) (OR= 18. 044, 95 % CI, 3. 952～～82. 392, P＜0. 01), and ≥30-yearold (OR = 6. 077, 95 0% CI, 1. 585～23. 299, P＜0. 01). Conclusion The optimal alkalized hydration solution is safe and effective to prevent early onset HC following URD-HSCT in combination with BuCy regimen. Male, aGVHD and ≥30-year-old were the risk factors for HC.     

Late relapse of a light‐chain myeloma as extramedullary plasmacytoma of the thyroid gland after second allogeneic stem‐cell transplantation

Abstract: We present a rare experience with a myeloma patient who had a late relapse as isolated extramedullary plasmacytoma of the thyroid gland after a second allogeneic transplantation. We give PET/CT scan findings at diagnosis and during follow up of the disease after subsequent management. The possible pathogenesis of the late extramedullary relapse of myeloma after allogeneic stem‐cell transplantation and management options are discussed.     

The significance of cytomegalovirus viremia at day 100 or more following allogeneic hematopoietic stem cell transplantation

We conducted a single‐center retrospective review of patients who had received allogeneic hematopoietic stem cell transplantation (HSCT) between January 2003 and December 2007, to assess the incidence and risk factors for late CMV infection and evaluate its effects on outcomes. Twenty of 49 HSCT recipients (41%) developed CMV infection at day ≥100 after transplant. Univariable analysis showed that having a matched unrelated donor, having early CMV infection, having a diagnosis of lymphoma, and receipt of antithymocyte globulin were risks for developing late CMV. On multivariable analysis, the occurrence of CMV prior to day 100 and lymphoma conferred a significant risk for late CMV infection. Of the 20 patients with late CMV infection, two patients manifested CMV disease (10%). Despite the relatively low incidence of CMV disease, patients with late CMV infection had a 4.8‐fold increased risk of death compared to patients without late CMV. Identifying patients at increased risk for developing late CMV infection may be important for prompting more intensive monitoring of infection late after HSCT, particularly because this manifestation of CMV is associated with poorer outcomes.     

Use of G‐CSF‐stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review

Chang Y‐J, Huang X‐J. Use of G‐CSF‐stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.
Clin Transplant 2011: 25: 13–23. © 2010 John Wiley & Sons A/S. Abstract: In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony‐stimulating factor (G‐CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen‐matched or haploidentical transplant settings, available data have established the safety of using G‐CSF‐stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G‐CSF‐primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft‐versus‐host disease that is associated with blood stem cell transplants. This review summarizes the growing body of evidence that supports the use of G‐CSF‐stimulated bone marrow grafts as an alternative stem cell source in allogeneic hematopoietic stem cell transplantation.     

Myeloablative allogeneic hematopoietic stem cell transplantation in elderly patients

This study aimed to evaluate the outcome following myeloablative allogeneic hematopoietic stem cell transplantation (SCT) among patients older than 50 yr of age. A total of 215 patients with a median age of 57 yr underwent allogeneic hematopoietic SCT for early (41%) or advanced (59%) hematologic malignancies. After a median follow-up of 36 months a 10-yr survival estimate of 56 +/- 6% could be assessed for patients in early disease stages while patients with advanced diseases showed a significantly decreased survival probability of 31 +/- 5% (p < 0.0002). Transplant related mortality (TRM) at day 100 and 365 post-transplant was 13% and 30% for early but increased to 21% and 49% for advanced disease stages. As major determinants of TRM advanced disease stage (p < 0.0001) and occurrence of grades II-IV graft-vs.-host disease (GVHD) (p < 0.0001) were identified. These results show that hematopoietic SCT following myeloablative conditioning is also applicable to elderly patients whereas disease stage and high-grade GVHD represent the essential prognostic factors for outcome.     

Feasibility of tacrolimus, methotrexate, and prednisolone as a graft-versus-host disease prophylaxis in non-T-cell-depleted haploidentical hematopoietic stem cell transplantation for children

In this study, we evaluated the feasibility of our graft-versus-host disease (GVHD) prophylaxis with tacrolimus, methotrexate, and prednisolone in non-T-cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) for children. Twenty-one consecutive patients including those with hematological malignancies (n = 11), solid tumors (n = 7), and non-malignancies (n = 3) were analyzed. Myeloablative and reduced intensity conditionings were carried out in 5 and 16 patients, respectively, and both of the regimens contained anti-human T-lymphocyte immunoglobulin. Twenty (95%) of the 21 patients achieved primary engraftment. Acute GVHD of grades II-IV and III-IV were observed in nine (47%) and one (5%) patient, respectively, all of which were controllable by steroids. Chronic GVHD was observed in eight (51%) of the 17 evaluable patients, and one of them developed steroid refractory chronic GVHD. Treatment-related mortality occurred in three patients (15%), as a result of acute pancreatitis, chronic GVHD, and EB virus associated lymphoproliferative disease. The median follow-up of the 13 survivors was 24 months, and the two-yr probability of overall survival was 68%. The Karnofsky performance scale score of the 13 survivors was 100%. These results indicated the feasibility of our GVHD prophylaxis in non-T-cell-depleted haploidentical HSCT for children.     

Impact of cyclosporine‐A concentration in T‐cell replete haploidentical allogeneic stem cell transplantation

This paper aims to study whether cyclosporine‐A (CSA) levels have an impact on the clinical outcome of patients with T‐cell replete haploidentical allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We analyzed 140 consecutive patients who had been given T‐cell replete haploidentical allo‐HSCT in our institute to assess the effect of CSA concentration in the early stages of allo‐HSCT on clinical outcomes, such as hematopoietic recovery, acute graft vs host disease (aGVHD), infection, disease‐free survival (DFS), and overall survival (OS). The median concentrations of CSA in the blood in the 1st, 2nd, 3rd, and 4th week after allo‐HSCT were 218, 235, 263, and 270 ng/mL, respectively. Additionally, 46%, 40%, 27%, and 18% of the patients had CSA blood levels below 200 ng/mL during those weeks. In total, 39 patients developed aGVHD (grade II‐IV), for a cumulative incidence of 27.8%, at a median of 32 days. Patients having a low CSA concentration (below 200 ng/mL) in the 3rd week had a higher cumulative incidence of grade II‐IV aGVHD (P = .02). In addition, multivariate logistic regression analysis showed that low CSA concentration (below 200 ng/mL) in the 3rd week was an independent risk factor of grade II‐IV aGVHD (P = .02; odds ratio = 2.66; 95% CI, 1.15‐6.17). However, CSA levels during the first 4 weeks did not have a significant impact on the patients’ hematopoietic recovery, infection, DFS, and OS. Our data indicated that adequate management of CSA levels during the peri‐engraftment period might improve clinical outcomes for those with T‐cell replete haploidentical allo‐HSCT.     

Clinical efficacy of prophylactic strategy of long-term low-dose acyclovir for Varicella-Zoster virus infection after allogeneic peripheral blood stem cell transplantation

Varicella-Zoster virus infection (VZV) has a high incidence post-allogeneic peripheral blood stem cell transplant (PBSCT). However, data regarding long-term acyclovir prophylaxis for VZV prevention are limited. We evaluated the clinical efficacy of long-term low-dose acyclovir prophylaxis for VZV infection after allogeneic PBSCT at the Princess Margaret Hospital (PMH), Canada and the Kyungpook National University Hospital (KNUH), Korea. The acyclovir prophylaxis regimen at PMH was acyclovir 400 mg/d orally until engraftment, and at KNUH was acyclovir 800 mg/d orally until immunosuppression discontinuation. Long-term acyclovir prophylaxis was given to 26/193 (14%) patients in the PMH group and 73/79 (92%) patients in the KNUH group. In the PMH group, 42 cases (22%) developed VZV infection, while six cases (8%) had VZV infection in the KNUH group (p = 0.005). With a median of 26.5 months of follow-up, the incidences of VZV infection at one and two yr were 15.8% and 20.7% in the PMH group, and 2.5% and 5.8% in the KNUH group, respectively (p = 0.001). By controlling the other potential risk factors for VZV infection in multivariate analysis, the use of long-term acyclovir was the only protective factor for VZV infection after allogeneic PBSCT (p = 0.04, hazard ratio = 0.296). Long-term use of acyclovir appears to be protective for VZV infection after allogeneic PBSCT, especially during the period of immunosuppressive therapy.     

Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations,protective associations,and outcomes

Dubberke ER, Reske KA, Srivastava A, Sadhu J, Gatti R, Young RM, Rakes LC, Dieckgraefe B, DiPersio J, Fraser VJ. Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes.
Clin Transplant 2009. DOI: 10.1111/j.1399‐0012.2009.01035.x
© 2009 John Wiley & Sons A/S. Abstract:  The purpose of this study was to evaluate risk factors, protective factors, and outcomes associated with Clostridium difficile‐associated disease (CDAD) in allogeneic hematopoietic stem‐cell transplant (HSCT) recipients. A case–control study was performed with 37 CDAD cases and 67 controls. In the multivariable logistic regression analysis, receipt of a third or fourth generation cephalosporin was associated with increased risk of CDAD (OR = 4.6, 95% CI 1.6–13.1). Receipt of growth factors was associated with decreased risk of CDAD (OR=0.1, 95% CI 0.02–0.3). Cases were more likely to develop a blood stream infection after CDAD than were controls at any point before discharge (p < 0.001). CDAD cases were more likely than controls to develop new onset graft‐vs.‐host disease (GVHD) (p < 0.001), new onset severe GVHD (p < 0.001), or new onset gut GVHD (p = 0.007) after CDAD/discharge. Severe CDAD was a risk factor for death at 180 d in multivariable Cox proportional hazards regression (HR=2.6, 95% CI 1.1–6.2). CDAD is a significant cause of morbidity and mortality in allogeneic HSCT patients, but modifiable risk factors exist. Further study is needed to determine the best methods of decreasing patients’ risk of CDAD.     

No effect of HLA‐C mismatch after allogeneic hematopoietic stem cell transplantation with unrelated donors and T‐cell depletion in patients with hematological malignancies

HLA‐C mismatch in unrelated donor's hematopoietic stem cell transplantation (HSCT) has been associated with poor patient outcome. However, the impact of HLA‐C mismatch in the context of HSCT combined with in vivo T‐cell depletion remains unclear. We therefore performed a single‐center, retrospective analysis of the clinical outcome on patients with hematological malignancies treated with allo‐HSCT, who underwent T‐cell depletion. The majority of the patients (n=276) received a HLA‐A, HLA‐B, HLA‐DRB1‐matched graft that were either also HLA‐C matched (n=260), or patients with the permissive HLA‐C*03:03/03:04 mismatch (n=16), while the remaining patients (n=95) received a HLA‐C‐mismatched graft (excluding HLA‐C*03:03/03:04 mismatches). We did not observe any significant differences between the HLA‐C‐matched patients (including the permissive HLA‐C*03:03/03:04 mismatch) and the HLA‐C‐mismatched patients regarding cumulative proportion surviving, graft failure, relapse‐free survival, relapse, or acute graft‐versus‐host disease. Our data suggest that in the context of high dose T lymphocyte‐depleting agents, HLA‐C matching is not essential for patients with hematological malignancies.     

肾移植联合造血干细胞移植诱导治疗七例

目的 探讨肾移植联合造血干细胞移植诱导治疗的安全性和有效性,并总结其经验.方法 2009年实施7例亲属活体肾移植联合造血干细胞移植,其中1例为供受者HLA抗原全相合,其余为半相合.肾移植前5d使用粒细胞集落刺激因子动员供者造血干细胞,术前1d采集供者造血干细胞.肾移植前3d受者开始接受全身淋巴照射,连续3d,肾移植术中给予受者抗胸腺细胞球蛋白50 mg,术后第2、4、6天输注供者造血干细胞.术后常规采用三联免疫抑制方案,监测受者血常规、淋巴细胞亚型变化及移植肾功能等情况.结果 全身淋巴照射后受者淋巴细胞数进行性降低,以B淋巴细胞(CD19+)的比例下降幅度最大,其他血细胞数量变化不大.HLA全相合受者诱导出30％～50％的嵌合体,其余受者仅诱导出1％～5％的嵌合体.术后随访3年,7例受者移植肾功能稳定,均未出现骨髓抑制和移植物抗宿主病,未增加感染风险.经移植肾活检证实,1例受者出现轻度急性排斥反应,其余6例受者未发生排斥发生.7例受者中,有3例减少了免疫抑制剂的用量.结论 肾移植联合造血干细胞移植诱导治疗的方案安全、有效.