Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation

We describe treatment, outcomes and prognostic factors for patients who relapse following transplantation with a reduced intensity conditioning regimen. Seventy consecutive patients with high-risk myeloid malignancies underwent transplant and 25 (36%) relapsed, a median of 120 days later. The median percentage of bone marrow blasts at relapse was 24, the median donor chimerism was 73% and new karyotypic abnormalities occurred in 8 out of 20 (40%) evaluable patients. Twenty-one patients (84%) received aggressive treatment for relapse, including chemotherapy (60%), second hematopoietic cell transplantation (HCT; 52%) and/or donor lymphocyte infusion (DLI; 12%). Thirteen achieved a complete response (CR) and four remain in CR. Median overall survival (OS) after relapse was 6 months (95% confidence interval=2.7-9.9 months), and actuarial 1 year OS was 24%. Most deaths were due to disease progression (17/20, 85%). We did not observe an advantage for cellular therapy (DLI or second transplant) compared to chemotherapy. Salvage therapy for relapse after reduced intensity HCT is feasible, associated with low treatment-related mortality, and may result in prolonged survival in select patients. Studies exploring the optimal treatment for relapse following reduced intensity HCT are warranted.     

Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning

Nonmyeloablative or reduced-intensity conditioning regimens have been used to condition elderly or ill patients with hematological malignancies for allogeneic hematopoietic cell transplantation (HCT). Initial mixed donor/host chimerism (i.e. the coexistence of hematopoietic cells of host and donor origin) has been observed in most patients after such transplants. Here, we describe both factors affecting engraftment kinetics in patients given a nonmyeloablative or a reduced-intensity conditioning, and associations between peripheral blood cell subset chimerism levels and HCT outcomes.     

Bortezomib with or without dexamethasone in relapsed multiple myeloma following allogeneic hematopoietic cell transplantation

We retrospectively evaluated the efficacy of bortezomib in 23 patients with multiple myeloma who had relapsed after allografting. Bortezomib was given as single agent to 9 patients (39%) and in combination with steroids in the other 14 (61%). Major toxicities were thrombocytopenia (10/23, 43%) and peripheral neuropathy (12/23, 52%). The overall response rate was 61% (14/23), including 22% (5/23) immunofixation-negative complete remissions. No significant differences in toxicity and response rates were seen between patients treated with bortezomib plus steroids and bortezomib alone. After a median follow-up of 6 months, progression free survival was 6 months. Twenty-one patients are alive, two and five in continuous very good partial and complete remissions, respectively.     

Outcome analysis of allogeneic hematopoietic stem cell transplantation for 41 patients with severe aplastic anemia

<正>Objective To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT)for patients with severe aplastic anemia(SAA).Methods A retrospective study was conducted in 41 SAA patients received allo-HSCT from Oct.2001 to May 2015.There were 27 males and 14 females with median age of 17(2-43)years old.Of them,24 received matched sib-     

Chimerism monitoring following allogeneic hematopoietic stem cell transplantation

Information regarding the chimeric status of hematopoietic stem cell transplantation (HSCT) recipients is of great significance when comparing different conditioning and prophylactic therapies. In recent years, short tandem repeats/variable number tandem repeats (STRs/VNTRs) have emerged as the best tool for chimerism monitoring. However, the polymorphisms of STR/VNTR markers vary within and between ethnic groups. The issue is further complicated in a heterogeneous population such as occurs in the Indian subcontinent. In the present study, we attempted to devise a robust scheme to identify a set of polymorphic STRs/VNTRs most suitable for chimerism evaluation in north Indian HCST recipients. At first, we did genotyping of 11 STR and one VNTR in 1000 randomly chosen north Indian individuals to quantify different diversity parameters. Resulting data indicated that ApoB3'HVR, FES, VWA, D3S1358 and D16S310 were most polymorphic loci with the average heterozygosity being 0.756+/-0.17. Furthermore, all markers were genotyped in 77 HLA-matched donor-recipient pairs to evaluate the informativeness in differentiating donor's and recipient's cells. A panel of seven markers (ApoB3HVR-D3S1358-HUM-THO1-VWF-1-D16S310-FES-VWA) differentiated 98.70% of donor-recipient pairs. This set of markers also successfully monitored the graft status in 14 HSCT cases during multiple time points following HSCT. The results were compared to the commercially available AmpF/STR SGM Plus multiplex PCR kit (Applied Biosystems, Foster City, CA, USA). Our findings established that the panel of seven markers we identified was more cost-effective and informative.     

异基因造血干细胞移植后早期结核分枝杆菌感染

目的:分析异基因造血干细胞移植后早期结核分枝杆菌感染的患病率、临床特征、诊断、治疗及预后.方法:对我院连续接受异基因造血干细胞移植的258例患者中确诊为结核分枝杆菌感染的6例患者进行回顾性分析及总结.结果:结核病的发生率为2.32%(6/258),在单倍型、非血缘、同胞相合移植3种不同移植方式中发生率分别为1.90%、...     

Intracranial hemorrhage following allogeneic hematopoietic stem cell transplantation

Charts and radiographs of 622 allogeneic hematopoietic stem cell transplant (HSCT) recipients, over a 20‐year period, were retrospectively reviewed for intracranial hemorrhage (ICH) following transplant. A total of 21 cases of ICH were identified (3.4%) including 15 cases of intraparenchymal hemorrhage (IPH), two cases of subarachnoid hemorrhage (SAH), and four cases of subdural hematoma (SDH). The median time from transplantation to the onset of ICH was 63 days (range, 6–3,488 days). The clinical features of post‐transplant ICH patients were similar and included hypertension, diabetes mellitus, chronic graft‐versus‐host disease (GVHD), systemic infection, and veno occlusive disease (VOD), recently referred to as sinusoidal obstruction syndrome, in addition to severe thrombocytopenia. Mortality rate was especially high (89%) after IPH with a median survival of 2 days (range, 0–148 days). In contrast, all patients with SAH or SDH following HSCT survived. The cause of post‐transplant ICH appears to be multifactorial, including thrombocytopenia, hypertension, acute GVHD, VOD, and radiation therapy. Most patients in our series displayed severe thrombocytopenia at the onset of ICH, even though adequate prophylactic platelet transfusions were given. By univariate analysis, cord blood transplantation, acute GVHD, systemic infection, and VOD were related to the incidence of ICH, whereas prior CNS episodes and radiation therapy did not reach statistical significance. A multivariate analysis with logistic regression identified acute GVHD as the only factor that significantly influenced ICH occurrence. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

髓系白血病异基因造血干细胞移植后髓外复发的危险因素分析

目的:探讨髓系白血病异基因造血干细胞移植(allo-HSCT)后髓外复发的危险因素及治疗策略。方法:回顾性分析2008年1月至2018年12月河南省肿瘤医院280例行allo-HSCT髓系白血病患者的临床资料,分析患者性别、原发病、移植前疾病状态、染色体、预处理方案、供者类型、移植前髓外浸润、移植物抗宿主病等指标。应用log-rank检验方法进行单因素分析,Cox比例风险模型进行多因素分析。结果:280例患者中髓外复发20例,复发率为7.14%(20/280),中位时间为移植后7.5(1~123)个月。髓外复发患者16例死亡,病死率80%(16/20)。单因素分析中,疾病类别、第2次完全缓解(CR2)/进展期、移植前髓外浸润、预处理不含全身放疗、染色体异常与髓外复发显著相关(P<0.05)。Cox回归显示,CR2/进展期(RR=3.468,95%CI 2.189~7.786)、染色体异常(RR=1.494,95%CI 1.020~2.189)、移植前髓外浸润(RR=8.627,95%CI 3.921~18.452)为髓外复发的独立危险因素。结论:髓系白血病allo-HSCT后髓外复发的预后较差,联合治疗可能延长患者的生存期,早期评估预防至关重要。     

Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in adult patients

Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplantation (HSCT) is still not well characterized. The aim of this study was to analyze the incidence and risk factors for the development of AIHA, as well as its prognosis and response to treatment in a series of patients undergoing allogeneic HSCT at a single institution. Between 1996 and 2004, 272 adult patients with a variety of malignant hematopoietic disorders underwent allogeneic HSCT. Direct antiglobulin testing was performed in routine pretransfusion compatibility testing or after clinical suspicion of AIHA. Twelve patients developed AIHA after HSCT at a median time of 147 days (range, 41-170). The 3-year cumulative incidence of AIHA was 4.44%. Eight cold antibodies and four warm antibodies were detected. Multivariate analysis shows that HSCT from unrelated donors (P=0.02) and the development of chronic extensive graft-versus-host disease (GVHD) (P=0.0004) were the only independent factors associated with AIHA. Two patients are still alive. AIHA was never the primary cause of death but added morbidity in patients with other concomitant complications. Patients undergoing HSCT from unrelated donors and those who develop chronic extensive GVHD are especially predisposed for this complication.     

Infectious complications following nonmyeloablative allogeneic hematopoietic stem cell transplantation

Abstract: Nonmyeloablative hematopoietic stem cell transplantation (NST) has been explored in hematological malignancies and solid tumors in an attempt to minimize treatment‐related toxicity. Whether this approach is associated with reduced risk of infectious complications is unclear. The aim of the current study was to evaluate the infectious complications in a series of 32 consecutive adult patients who received NST at our institution. Peripheral blood stem cell grafts (n=30) or marrow grafts (n=2) were infused from human leukocyte antibody (HLA)‐matched sibling (n=30), partially matched related (n=1), or unrelated (n=1) donors. Neutropenia developed in two‐thirds of patients and lasted 16 days. Acute graft‐versus‐host disease (GVHD) grade II to IV was observed in 25% of patients, whereas 35% of patients had signs of extensive chronic GVHD. Twenty‐two patients (69%) had at least one significant infectious episode. Bacteremia occurred in 19% of patients (n=5 gram‐positive, n=1 gram‐negative microorganisms). Cytomegalovirus (CMV) infection was observed in 10 out of 28 (36%) evaluable patients; 4 of these had recurrent or persistent CMV antigenemia requiring a second‐line treatment, but eventually the viremia cleared. No patients experienced CMV disease. Fungal infections were documented in five (16%) patients, comprising invasive fungal infections in two cases and mucosal fungal infections in three. Four patients died of transplant‐related causes, and three of these died before day +100. Infection was considered the primary cause of death in one patient (pulmonary aspergillosis) and contributed to death in another two. The actuarial probability of nonrelapse mortality at 100 days was 10% (95% confidence interval, 3–26%). Our preliminary results suggest that NST is associated to a low incidence of bacteremia or fungal and viral infections. Whether these findings would translate into an improved overall survival needs to be confirmed in larger prospective studies.     

Bronchiolitis obliterans following pediatric allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans (BrOb) is a well-recognized complication of allogeneic hematopoietic stem cell transplantation (HSCT). It is associated with substantial morbidity and mortality in adult patients. However, the incidence and morbidity of this complication have not been well described in the pediatric population. We report our experience of BrOb in 216 pediatric allogeneic HSCT patients between 1 January 2001 and 31 December 2005. In total 18 of 216 patients developed BrOb during this time. The diagnosis of BrOb was based on pulmonary function abnormalities, radiographic findings or lung biopsy. In total 14 of 18 patients with BrOb received stem cells from unrelated donors. In total 17 of 18 patients received bone marrow as a stem cell source, and 1 received peripheral blood stem cells. All pediatric patients in this report had a known risk factor for BrOb, most commonly chronic GVHD (l8 of 18 patients). Additionally, 7 of 18 patients had either toxic lung injury or virally mediated pulmonary disease before the diagnosis of BrOb. With a median of 45.1 months of follow-up, the outcomes were 5 of 18 patients died of lung disease, 2 died of other causes, 3 had progressive lung disease, 6 achieved partial resolution of disease and 2 had stable disease. BrOb, while uncommon, is associated with considerable morbidity and mortality in pediatric HSCT.     

Outcome of allogeneic stem cell transplantation in patients with myelofibrosis

Myelofibrosis, either de novo or following pre-existing hematologic diseases, can be cured by allogeneic hematopoietic stem cell transplantation (SCT), but SCT is associated with significant morbidity and mortality, making the choice and timing of transplantation difficult. In all, 20 patients (seven female and 13 male), with a median age of 45 years (range 22-57 years), with idiopathic myelofibrosis (n = 12), post-thrombocythemic (n = 3) or post-polycythemic (n = 2) myeloid metaplasia or leukemic transformation (n = 3), underwent allogeneic SCT at our center between 1994 and 2003. With regard to the pre-transplant presence of risk factors such as hemoglobin levels < or =10 mg/dl, grade III marrow fibrosis or peripheral blast counts >1%, patients were divided into high- and low-risk groups. The estimated 3-year survival post transplant was 38.5% for all patients. The 3-year probability of survival within the high-risk group (n = 11) characterized by the presence of at least two risk factors was 16%. Low-risk patients (n = 9) with at most one risk factor had an estimated 3-year survival of 67%. Thus, previously defined risk determinants for the outcome of allogeneic transplantation for myelofibrosis may provide useful information facilitating treatment strategies. Our data suggest that transplantation should be taken into consideration before poor prognostic variables develop.     

Flow cytometric findings in platelets of patients following allogeneic hematopoietic stem cell transplantation

Following allogeneic hematopoietic stem cell transplantation (HSCT) patients may have an increased bleeding tendency in spite of a normal platelet count. Moreover, an association between chronic graft-versus-host disease (cGVHD) and a thrombophilic state has been observed. Platelet receptors and granules from 27 patients following HSCT (13 without cGVHD, 14 with cGVHD) were evaluated by flow cytometric analysis and compared to 62 healthy controls. Platelets from HSCT patients stained weakly with mepacrine indicating a reduced content of dense bodies, whereas no significant degranulation reaction of alpha granules and lysosomes was detectable. In addition, a lower surface expression of GP Ia/IIa was observed, indicating an acquired thrombocytopathy. The surface receptors are activated in HSCT patients, which could be seen by the lower surface expression of GP Ib internalized during the activation process and elevated levels of LIBS-1 and PAC-1 antibody binding. Patients with cGVHD had a seven-fold increased ratio of microparticles. This study demonstrates platelet receptor and granule defects in patients following HSCT. The key role of platelets in HSCT-associated hemostatic disorders is underscored by the high levels of circulating microparticles in cGvHD patients which might explain the thrombophilic state in these patients.     

Second hematopoietic stem cell transplantation for the treatment of graft failure, graft rejection or relapse after allogeneic transplantation

Failure to engraft after hematopoietic stem cell transplantation (graft dysfunction) or to sustain engraftment (graft rejection) is a formidable complication due to many possible factors. These include inadequate stem cell numbers, infections, graft-versus-host disease and immunological mediated processes. Fortunately, this complication is uncommon and can be overcome by additional hematopoietic stem cell infusions. Multiple treatment alternatives have been explored including hematopoietic growth factors, additional infusions of stem cells alone, with augmented immunosuppression or with additional cytotoxic therapy. Various sources of the additional stem cells are feasible including the original donor, using another donor, using stem cells collected from the marrow or after cytokine mobilization from the peripheral blood. This report will overview this complication and review the various studies that have attempted to define both cause and therapy. However, a lack of well-designed prospective studies has made definitive recommendations difficult although basic principles have been established.     

Cause of pleuroparenchymal fibroelastosis following allogeneic hematopoietic stem cell transplantation

Late-onset noninfectious pulmonary complications (LONIPCs) are life-threatening complications after hematopoietic stem cell transplantation (HSCT). Pleuroparenchymal fibroelastosis (PPFE) is a LONIPC, but its etiology remains elusive. Chronic graft-versus-host disease (cGVHD) and alkylating agents used for conditioning have been considered possible causes of PPFE. Therefore, to investigate the primary cause of PPFE in allogeneic HSCT, we compared three secondary PPFE groups, namely, the post-lung-transplantation, post-autologous-HSCT or chemotherapy-alone, and post-allogeneic-HSCT groups, and focused on the coexistence of bronchiolitis obliterans (BO), a typical phenotype of cGVHD. We found a trend towards higher rates of PPFE with BO in the post-allogeneic-HSCT and post-lung-transplantation groups (71% and 90%, respectively) than in the post-autologous-HSCT or chemotherapy-alone group (25%). The incidence of BO following allogeneic HSCT is reportedly <10%. If PPFE in the post-allogeneic-HSCT group has no association with BO and is induced by alkylating agents rather than cGVHD, the incidence of BO in PPFE in this group is estimated to be <10%, which is inconsistent with our data (71%). Thus, this study suggests that PPFE following allogeneic HSCT could be mainly induced by cGVHD because the majority of cases are associated with BO, a typical phenotype of cGVHD.