Enteral feeding and early outcomes of patients undergoing allogeneic stem cell transplantation following myeloablative conditioning

The purpose of this study was to evaluate the impact of enteral nutrition on early outcome of patients after myeloablative allogeneic stem cell transplantation (allo-SCT). From January 2001 to January 2003, 22 patients agreed to receive enteral nutrition via a nasogastric feeding tube; the remaining 23 patients received parenteral nutrition (n=22) or standard oral feeding (n=1). Early complications and factors influencing 100-day overall survival (OS) were investigated. Patients who received enteral nutrition developed less often acute-grade III/IV graft-versus-host disease (18%) than those who did not (35%) (P=0.011). In addition, this group showed lower mortality from infection during the first 100 days after transplantation. In multivariate analyses, only the absence of enteral nutrition was found to adversely influence 100-day OS with a hazard ratio of 8.3. Enteral nutrition is a safe and effective method for feeding allo-SCT patients. A randomized trial is warranted to confirm its advantage on early patient outcome.     

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.     

Comparative outcomes of reduced intensity and myeloablative allogeneic hematopoietic stem cell transplantation in patients under 50 with hematologic malignancies

We have conducted a direct comparison of the outcomes of reduced intensity and myeloablative conditioning in younger adults with hematological malignancies<50 yr. One hundred and five patients received transplants from human leukocyte antigen (HLA)-matched donors, via either reduced intensity (n=35) or myeloablative conditioning (n=70). The median ages of the reduced intensity and myeloablative groups were 36 and 33 yr (p=0.014). Neutrophil engraftment (i.e. time to absolute neutrophil count>0.5x10(9)/L) occurred more rapidly in the reduced intensity group (median: 10 d; range: 0-21 d) than in the myeloablative group (median: 18 d; range: 11-38 d; p<0.0001). The incidence of grades 2-4 acute graft-vs.-host disease were similar between the reduced intensity and myeloablative groups, at 17% vs. 24% respectively (p=0.40). The cumulative incidence of day 100 non-relapse mortality was 18% in the reduced intensity group, and 21% in the myeloablative group (p=0.88). The overall two-yr survival rates were 43% in the reduced intensity group, and 35% in the myeloablative group (p=0.72). In conclusion, reduced intensity transplantation yielded outcomes comparable with those of myeloablative transplantation in patients under 50 with hematological malignancies.     

Nephrotic syndrome in patients after successful myeloablative allogeneic hematopoietic stem cell transplantation: clinical findings obtained from four transplanted patients

We experienced four patients who suffered from nephrotic syndrome after a successful allogeneic hematopoietic stem cell transplantation (HSCT). These cases were seen in the nineteen-year period from September, 1986 to June, 2005. Our data showed that the incidence of nephrotic syndrome was 0.51% (3 out of 585 HSCT patients) in our hospital. Pathological findings of their renal biopsy specimens revealed that 3 patients had membranous nephropathy and that one patient had minimal change disease. Three patients were positive for anti nuclear antibody. Administration of prednisolone or cyclosporine improved the nephrotic syndrome, leading all patients to a complete or almost complete remission. The nephrotic syndrome occurred at 17 to 25 months after HSCT and accompanied the relapse of chronic graft-versus-host disease (GVHD), possibly due to the termination or a decrease of immunosuppressant administration in all patients. This suggests that immunological abnormality associated with chronic GVHD may be partly involved.     

Favorable long-term outcome of nephrotic syndrome after allogeneic hematopoietic stem cell transplantation

BACKGROUND: The development of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (HS-CT) is a rare complication with few long-term outcome data. PATIENTS: Clinical course and long-term outcome of three adult patients and one child with NS after HSCT (total number of transplants n = 533) are presented. RESULTS: The median age at onset of NS was 35 years (range 15 - 56), occurring at a median of 17 months (range 11 - 21) after HSCT. Discontinuation of cyclosporine A (CSA) prior to onset of NS was a consistent feature and occurred a median of 6 months (range 2 - 10 months) prior to the development of NS. The histopathological lesion was membranous nephropathy (n = 3) and membranoproliferative glomerulonephritis Type 1 (n = 1). History of acute or concomitant clinically apparent chronic graft versus host disease (GVHD) was present in all cases except the pediatric patient who had abundant DR-activated cytotoxic T cells without evidence of viral reactivation. Long-term immunosuppression for 11 - 36 months with steroids (n = 1), combined steroids and CSA (n = 2) or CSA alone in steroid-refractory NS (n = 1) resulted in sustained remission of the NS in all patients (12 months - 8 years off immunosuppression). CONCLUSION: NS after HSCT seems to be etiologically related to subclinical or overt chronic GVHD, which flares up after discontinuation of CSA. However, resumption of immunosuppression can reverse NS as well as GVHD and induce favorable sustained long-term remission.     

The relationship between body mass index and outcomes in leukemic patients undergoing allogeneic hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is being used increasingly in an attempt to cure many hematological disorders. Obesity has become a world wide phenomenon and is a known risk factor for numerous medical conditions, but its role in transplant outcomes remained controversial. Total of 192 patients with acute leukemia who underwent sibling HLA matched HSCT were analyzed to find the effect of pre-transplant body mass index (BMI) on transplant outcomes such as time to engraftment, infections, graft vs. host disease (GvHD), and overall survival (OS) for the period of three yr (April 2006-March 2009). There was a significant correlation between higher pre-transplant BMI and shorter engraftment time (p = 0.010); but no relation between BMI and GvHD, infection, and OS was found. The results of this study showed that patients with higher BMI may have a shorter engraftment time; but lower, although not significant, survival rate compared to non-obese patients.     

非亲缘异基因造血干细胞移植治疗白血病患者疗效观察

目的探讨非亲缘异基因造血干细胞移植(URD-HSCT)治疗白血病的效果。方法 10例白血病患者(急性髓细胞白血病第1次缓解期3例,急性淋巴细胞白血病第1次缓解期3例、第2次缓解期1例,慢性髓细胞白血病慢性期3例)接受URD-HSCT治疗。所有患者均采用经典的或改良的白消安联合环磷酰胺预处理方案。4例采用环孢素+短程甲氨蝶呤+吗替麦考酚酯预防移植物抗宿主病(GVHD),另6例患者加用抗胸腺细胞免疫球蛋白。输注供者有核细胞中位数为5.6×108/kg,CD34+细胞中位数为3.3×106/kg。结果除1例在移植后早期死亡不能评估外,其余9例均证实植活。发生急性GVHDⅠ度3例和Ⅱ度、Ⅲ度、Ⅳ度各1例,局限性慢性GVHD7例;发生真菌感染4例、CMV血症3例、出血性膀胱炎3例。10例患者目前无病存活7例,生存期为3个月～10年。结论 URD-HSCT安全而耐受性好,移植相关并发症仍是影响URD-HSCT效果的主要问题。     

Risk factors and severe outcome in thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation

BACKGROUND: Thrombotic microangiopathy (TMA) has been described as severe complication after hematopoietic stem cell transplantation (HSCT). The principal aim of this study was to focus the incidence and the outcome of TMA in the era of more complex HSCTs. METHODS: We analyzed the role of some predicting factors for the incidence and the outcome of TMA after HSCT. We enrolled 539 consecutive patients (307 males, median age 31 years) undergoing HSCT from match or mismatch human leukocyte antigen family donor (314) or match/mismatch unrelated (195) and haploidentical donor (30) for malignant or nonmalignant diseases. TMA diagnosis was performed by homogeneous clinical and laboratory criteria. RESULTS: Sixty-four of 539 patients presented TMA (11,87%) and the five-year cumulative incidence of TMA was 14% (HR=0.13). Fifty nine of 64 patients were affected by malignant and 5/64 by non-malignant diseases. On multivariate analysis, TMA occurrence was influenced by graft versus host disease >grade II (P=0.0001), donor type (P=0.029), gender (P=0.0233), total body irradiation based conditioning regimen (P=0.0041). Three factors for TMA outcome proved to be statistically significant by multivariate analysis: age (P=0.009), donor type (P=0.0187) and TMA index (P=0.029). The TMA mortality rate was 50%. The outcome was influenced by defibrotide (P=0.02 in univariate analysis). CONCLUSIONS: The study underlines the possibility of finding out which patients are more prone to developing post-HSCT TMA, and identifies which risk factors are more frequently associated with a dismal outcome after TMA.     

Soluble heat shock protein 70 members in patients undergoing allogeneic hematopoietic cell transplantation

BackgroundHeat shock proteins (HSP) are highly conserved immunogenic proteins serving as potent danger signals. They are upregulated under stress conditions like fever and hypoxia. Extracellular HSP are involved in antigen presentation, cytokine release and maturation of antigen presenting cells.MethodsThe release of the inducible members of the HSP70 family, Hsp72 and Hsp70B′, into the serum of 20 patients undergoing allogeneic hematopoietic cell transplantation and 20 healthy donors was evaluated using enzyme linked immunosorbent assay (ELISA) kits.ResultsEight patients (40%) did not receive anti-thymocyte globulin (ATG) for prophylaxis of graft versus host disease (GvHD). These patients had no detectable or low serum levels of Hsp72 (n = 3, 0.03 to 1.92 ng/ml) which were in line with levels detected in 20 healthy individuals (p = 0.07). Measurable HSP was not associated with any medication or transplantation-related procedures. In twelve patients (60%) receiving ATG, detected high levels of HSP reflected cross-reactivity of the rabbit-derived ATG with the anti-rabbit antibody used in the ELISA.ConclusionsAssumed HSP70 expression detected such ELISA has to be regarded carefully after ATG application. Neither radiochemotherapy, nor inflammation or sepsis during aplasia induced HSP70 release into the serum. Thus, soluble HSP70 may not be involved in the pathogenesis of acute GvHD.     

自体造血干细胞移植后序贯异基因造血干细胞移植治疗浆母细胞淋巴瘤一例

正浆母细胞淋巴瘤(plasmablastic lymphoma,PBL)是一种罕见的非霍奇金淋巴瘤,来源于B细胞,侵袭性高、预后差,具有独特的临床特征。宁波市第一医院血液科采用自体造血干细胞移植(autologous hematopoietic stem cell transplantation,auto-HSCT)后序贯异基因造血干细胞移植(allogeneic     

Long‐term outcomes of antithymocyte globulin in patients with hematological malignancies undergoing myeloablative allogeneic hematopoietic cell transplantation: a systematic review and meta‐analysis

Antithymocyte globulin (ATG) has shown efficacy in preventing acute GVHD (aGVHD) in allogeneic hematopoietic cell transplantation (allo‐HCT), but its efficacy in chronic GVHD (cGVHD) and long‐term outcomes remains controversial. We conducted a systematic review and meta‐analysis to evaluate potential benefit and risk of prophylactic ATG use in myeloablative HCT. We searched Pubmed, EMBASE, Cochrane databases, and included 10 trials (two RCTs and eight retrospective) comparing ATG use vs. control with a total of 1859 patients. The median follow‐ups were over two yr. Outcomes assessed included overall cGVHD, extensive cGVHD, overall survival (OS), disease‐free survival, relapse, and causes of death. Our results showed ATG significantly decreased overall cGVHD (RR = 0.59; 95% CI: 0.53–0.66, p < 0.00001), extensive cGVHD (RR = 0.34; 95% CI: 0.25–0.47, p < 0.00001). Pooled results also showed ATG use was associated with a marginal increased risk of relapse (RR = 1.28; 95% CI: 1.01–1.63, p = 0.04), and a non‐inferior OS (HR = 0.86; 95% CI: 0.74–1.01, p = 0.06). We conclude prophylactic use of ATG exerts a favorable effect in reducing cGVHD without survival impairment in a long term, although a higher relapse rate is a major threat.     

异基因造血干细胞移植患者术后并发脑脓肿的护理

对1例骨髓增生异常综合征患者行异基因造血干细胞移植,术后并发脑脓肿。对患者加强护理,即密切监测患者病情,及时发现症状并采取对应的护理措施,包括颅内压增高的护理、肢体运动障碍的护理、发热(抗感染)的护理、心理护理、预防出血的护理、并发症的观察。结果患者移植成功,脑脓肿得到有效控制,顺利出院。提出避免引起颅内压增高的因素、控制感染、预防出血、促进造血重建,为患者制订个体化的康复计划,可使脑脓肿得到控制,促进康复。     

Fatal varicella zoster virus encephalitis in two patients following allogeneic hematopoietic stem cell transplantation

BACKGROUND: Reduced cellular immunocompetence following allogeneic hematopoietic stem cell transplantation (aHSCT) increases susceptibility to viral infections. Varicella zoster virus (VZV) reactivation in this setting most commonly manifests as dermatomal herpes zoster but in some cases life-threatening VZV encephalitis occurs. STUDY DESIGN/RESULTS: We describe the cases of two patients who presented with shingles 3 and 18 months, respectively, after HLA-matched peripheral blood stem cell transplantation (PBSCT). Unfortunately, in the further clinical course both patients developed fatal VZV encephalitis, despite initial high-dose intravenous therapy with acyclovir and in one case with additional VZV-immunoglobulin. CONCLUSION: These two cases suggest that rapid intervention with systemic treatment is warranted and raise the question whether initial combination therapy with intravenous acyclovir and foscarnet, VZV vaccination or long-term low-dose acyclovir are needed to improve treatment and clinical outcome in immunocompromised patients, having undergone allogeneic HSCT.     

Second allogeneic hematopoietic stem cell transplantation: a treatment for graft failure

We evaluated the results in 20 recent patients treated with a second hematopoietic stem cell transplantation (HSCT) after graft failure (GF). There were 10 children <18 yr of age. Ten patients had a non-malignant disease, and the other 10 had a malignant disease. In most of the transplantations, fludarabine-based reduced intensity conditioning (RIC) was given. Bone marrow was given to 11 patients, peripheral blood system cell (PBSC) in seven and cord blood to two patients. For the second transplantation (n = 20), a new donor was used in nine cases, while the initial donor was used in 11 transplants. Eight patients (40%) suffered from a second GF. Five of these patients were treated with a third HSCT. The probability of survival was 65% one yr and 60% three yr after the second HSCT. No difference in survival was found between patients transplanted with a new donor (56%) compared to those using the original donor (64%). The three-yr survival was 70% for children compared to 50% for adults (p = ns). Patients with a non-malignant disorder showed a three-yr survival of 90% compared to 20% in patients with a malignant disease (p = 0.005). We concluded that re-transplantation using RIC is a valid option for GF, especially in patients with non-malignant disorders.