Stem‐cell transplant preparative regimens

Abstract: Owing to the relatively high probability of recurrent disease in patients receiving hematopoietic stem‐cell transplantation (HSCT) for malignancies, further development of new preparative regimens is warranted. Based on the data presented, one can predict that it will continue to be difficult to identify HSCT regimens that are more effective. Incremental improvements are expected to be small, difficult to measure, and will require inclusion of very large numbers of patients. Controlled trials to evaluate the effectiveness of specific treatment regimens for specific groups of patients will require to be conducted only by centers with large numbers of patients, or co‐operative groups. Development of HSCT regimens with low mortality and a minimum of morbidity, without compromising efficacy, are needed. This may be accomplished through the use of agents to protect normal, non‐hematopoietic tissues from regimen‐related toxicity (RRT), further exploration, and expansion of applications of targeted radiolabeled antibody approaches and mixed chimerism approaches. The future holds much work, but great promise, in the development of new HSCT regimens.     

Intensification of therapy using hematopoietic stem‐cell support for high‐risk neuroblastoma

Abstract: The use of new strategies for dose intensification using peripheral blood stem cell or autologous purged bone marrow rescue has raised expectations for cure in advanced neuroblastoma, although conflicting reports exist regarding the efficacy of these approaches. Using risk groups based on both biological and clinical staging, the Children's Cancer Group and the Pediatric Oncology Group have agreed upon common prognostic criteria for treatment stratification. We summarize below the prognostic classification and treatment approaches that have improved the overall outcome for children with advanced neuroblastoma. Intensive induction therapy, myeloablative therapy, hematopoietic stem cell purging, and post-transplant therapy for minimal residual disease all have an important role in the treatment. Possible future improvements may incorporate more tumor-specific therapy with targeted radiotherapy, monoclonal antibodies, tumor vaccines, and differentiating agents.     

T‐cell recovery following marrow transplant: Experience with delayed lymphocyte infusions to accelerate immune recovery or treat infectious problems

Abstract: All forms of hematopoietic stem‐cell transplantation are complicated by delayed immune reconstitution, which results in an increased risk of infectious complications and relapse of disease. Donor lymphocyte infusions have been used in an attempt to enhance immune recovery and for the prevention and treatment of specific infections following transplantation. While there is little data to support the use of donor lymphocytes for the enhancement of general immune function post‐transplant, unselected and virus‐specific donor T cells may have efficacy for the prophylaxis and treatment of infections and disease caused by Epstein–Barr virus (EBV) and cytomegalovirus (CMV). While donor lymphocyte infusions may cause significant morbidity and mortality, they are a novel and potentially powerful approach for the treatment of frequently fatal post‐transplant infectious complications.     

Allogeneic hematopoietic stem cell transplantation for Chediak–Higashi syndrome

The clinical outcome of allogeneic HSCT was retrospectively analyzed in eight patients with CHS. In total, six of these eight patients are alive. Four of five patients transplanted with MAC achieved prompt engraftment, and three of the four patients, including two patients with AP before transplant, are alive without disease. In contrast, three patients transplanted with RIC without active AP disease achieved prompt engraftment and survive long term. RIC‐HSCT might be an alternative treatment for CHS similar to other types of HLH, at least for patients without active AP disease.     

Etiology and outcome of graft failure in pediatric hematopoietic stem cell transplant recipients

PURPOSE: To determine the incidence, etiology and outcome of graft failure in pediatric allogeneic bone marrow transplant (BMT) recipients. PATIENTS AND METHODS: Patients with primary or secondary graft failure were identified by database review. A retrospective chart review was performed. Etiologic factors were identified and assessed for statistical significance. RESULTS: 309 children underwent allogeneic BMT during the time interval studied. Four cases of primary graft failure and 7 cases of secondary graft failure occurred. Nonmalignant diagnosis, lower total nucleated cell (TNC) dose, and conditioning without total body irradiation were associated with a higher incidence of graft failure. Donor source, donor/recipient CMV status, CD34+ cell dose, and alloimmunization were not associated with graft failure. CONCLUSIONS: Graft failure is a relatively uncommon occurrence in pediatric patients. Autologous reinfusion may allow time to prepare the patient for a second transplant and decrease complications associated with aplasia. More immunosuppressive conditioning regimens may decrease the incidence of graft failure, particularly in patients with non-malignant diseases or those with lower stem cell doses. More frequent monitoring of chimerism by VNTR analysis may detect late graft failure earlier and allow for more rapid intervention.     

异基因造血干细胞移植治疗噬血细胞综合征

噬血细胞综合征又称噬血细胞性淋巴组织细胞增生症,分为原发性和继发性两大类.对于家族性噬血细胞综合征(familial hemophagocytic lymphohistiocytosis,FHL)和难治性EB病毒相关噬血细胞综合征(EBV-HLH),异基因造血干细胞移植是目前唯一有效的治疗手段,但其鉴别诊断尤为困难,移植后多种并发症以及高病死率也受到越来越多人的关注.该文总结了近年来异基因造血干细胞移植治疗FHL和难治性EBV-HLH在诊断、预处理方案、移植后并发症、死亡原因分析及预后等方面的研究进展.     

Allogeneic hematopoietic stem cell transplantation against recurrent rhabdomyosarcoma

The prognosis of high-risk rhabdomyosarcoma (RMS) with metastatic or recurrent disease remains poor. We report a 6-year-old girl who successfully underwent allogeneic hematopoietic stem cell transplantation against recurrent metastatic alveolar RMS. The disease recurred at distant lymph node metastasis with bone marrow involvement. After chemotherapy and radiotherapy for the metastatic site, she underwent allogeneic bone marrow transplantation during complete remission from her 5/8 HLA-matched father. She developed acute graft-versus-host disease after preemptive donor lymphocyte infusion and remains in a disease-free condition for 31 months after transplantation. A graft-versus-tumor effect through allogeneic immune cells might produce a beneficial effect for high-risk RMS.     

Immunological recovery post‐hematopoietic stem cell transplantation: Role of prophylactic prevention of infection in post‐transplant period

Abstract: Immunological recovery post-hematopoietic stem cell transplantation is variable. This depends upon the type of transplantation, source of hematopoietic stem cells for transplantation, prophylactic treatment for graft-versus-host disease and ongoing therapy for the treatment of graft-versus-host disease with immunosuppressive agents. Periodic numerical and functional assessment of recovery of the immune system after transplantation can identify the patients with inadequate immune system who are at risk for development of infectious complications. These patients should receive prophylactic therapy to decrease infection-related morbidity and mortality associated with transplantation procedures.     

Long‐term follow‐up in hematopoieticstem‐cell transplant patients

Abstract: Hematopoietic stem‐cell transplantation (HSCT) has increasingly become an accepted treatment for many childhood diseases and disorders. Potential HSCT recipients can be children with hematological malignancies or solid tumors, as well as congenital and acquired disorders. In the past decade, the use of HSCT in the treatment of pediatric disorders has grown exponentially while advances in supportive care have improved survival rate, contributing to a rapidly growing population of transplant survivors. Although numerous similarities can be found between pediatric and adult long‐term HSCT survivors, this article provides a brief overview of the pediatric patients, emphasizing the aspects of surveillance and late effects. Understanding the long‐term complications that can occur after HSCT is important in determining the appropriate evaluations and medical treatment for the patient involved. The goal of this article is to assist caregivers in providing optimal care for long‐term survivors of HSCT. The initial section of this work comprises the three major causes of late effects in HSCT. It will then encompass a system review of the different potential complications that are seen with HSCT.     

Allogeneic hematopoietic stem cell transplantation in children with sickle cell disease

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment for sickle cell disease (SCD), being successful in around 85-90% of patients. Mortality and long-term morbidity (including infertility, gonadal failure, and chronic graft-vs.-host disease) associated with conventional approaches curtail the number of patients who undergo allo-HSCT. Recently, it has been demonstrated that cord blood is as effective as and possibly safer than bone marrow in pediatric patients with SCD. Likewise, transplant strategies based on the use of reduced-intensity regimens and the induction of mixed chimerism have been explored to decrease allo-HSCT short- and long-term complications.     

T cell replete–haploidentical second hematopoietic stem cell transplantation for primary graft failure in pediatric patients with hematologic malignancies

GF is one of the fatal complications of allogeneic HSCT. To rescue patients with primary GF, a second HSCT should be conducted as soon as possible, but the optimal donor source and technique have yet to be established. In this study, we retrospectively analyzed six children with hematologic malignancies who received TCR‐haploidentical second HSCT for primary GF. The median interval between the prior HSCT and the second HSCT was 37.5 days. All patients received fludarabine and ATG containing reduced‐intensity re‐conditioning before the second HSCT. All patients, except one who died early, achieved both neutrophil and Plt engraftment at a median time of 15 and 33 days, respectively. Chimerism analysis showed that all engrafted patients achieved complete donor chimerism within 3 weeks. Four patients developed acute GVHD, and three patients developed chronic GVHD. TRM occurred in two patients. Median follow‐up of the four survivors was 6.8 years, and all remained in sustained remission until the last follow‐up. These results suggested that a TCR‐haploidentical second HSCT for pediatric patients is feasible, and this approach may provide a potent option for children with primary GF.     

Infant botulism: A review in South Australia (1980–89)

Between March 1980 and March 1989 there were six identified cases of infant botulism. The presenting symptoms were predominantly poor feeding, lethargy and constipation, and the presenting signs were predominantly hypotonia, weak gag reflex and respiratory difficulty. All required intensive care and prolonged hospital stays. Recovery was eventually complete in all cases. Infant botulism is an uncommon condition but early recognition with adequate intensive care usually results in complete recovery.     

Allogeneic hematopoietic stem cell transplantation for infants with idiopathic myelofibrosis

IMF is a rare disease in children that can present during infancy and has a protracted course. The only known curative approach for this disease in adult patients is allogeneic HSCT. There are very few reports describing the long‐term outcome of young children following stem cell transplantation for IMF. We report on eight patients less than two yr of age with IMF that did not resolve with supportive care measures. All patients underwent myeloablative conditioning regimen with busulfan and cyclophosphamide ± ATG followed by HSCT from matched related (n = 6) or unrelated donor (n = 2). All patients achieved neutrophil and platelet engraftment. Four patients had grade II‐III acute GVHD, and chronic GVHD developed in five patients (three mild and two severe). At a median follow‐up of eight and a half yr (0.7–9), all patients are alive with complete resolution of their hematologic manifestations. At the last follow‐up, all patients had normal endocrine function except for one patient who developed hypothyroidism. To date, this is the largest cohort of young children with IMF treated successfully with HSCT, with the longest duration of follow‐up. In conclusion, our study showed that HSCT is a curative option for infants with IMF.     

Allogeneic hematopoietic stem cell transplantation in congenital disorders: A single‐center experience

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is the treatment of choice for a variety of congenital disorders. We report the experience of children affected by congenital diseases other than bone marrow failure syndromes who received allo‐HSCT over a period of 25 years at G. Gaslini Paediatric Research Institute. HSCTs were performed in 57 children with congenital diseases (25 with congenital immunodeficiencies, 10 with severe combined immunodeficiencies, and 22 with metabolic diseases). Overall survival rate at 3 years in the whole group of patients was 76.9%, with a trend in favor of better outcome in children with metabolic diseases and in those who received cord blood cells (85.9%) vs bone marrow cells (72.4%).     

Cervical epidural analgesia for a cancer child at home

A cervical epidural catheter was placed in a 32-month-old girl suffering from painful bone metastases of a relapsing neuroblastoma in the left forearm. This therapeutic approach was chosen because oral morphine had failed to provide analgesia while producing intolerable side effects. The epidural injection of a mixture of morphine and bupivacaine provided complete analgesia with no side effects. This enabled the parents to take care of their child at home until the end, 35 days later. © 1994 Wiley-Liss, Inc.     

异基因造血干细胞移植治疗儿童血液病

目的观察异基因造血干细胞移植对儿童血液病的治疗效果。方法采用异基因造血干细胞移植治疗15例儿童血液病,其中非血缘脐血移植9例,同胞脐血移植3例,同胞外周血干细胞移植2例,同胞骨髓移植1例。采用马利兰/环磷酰胺(BU/CY)或环磷酰胺/全身照射(CY/TBI)为基础的预处理的方案。结果14例患儿植入成功,白细胞的植入时间各组间差异无统计学意义;脐血移植血小板的植入时间较骨髓或外周血延迟(P<0.05)。主要并发症为CMV感染和复发,11例患儿生存,其中10例无病存活(占66.7%),存活最长时间为6年。Kaplan-meier生存曲线提示:1年生存率为76.6%,预计5年生存率为57.4%。结论脐血移植具有GVHD轻且较容易控制、搜寻时间短等优点,对儿童患者具有广泛的应用前景。     

Priorities and practice in tropical paediatrics

More than 14 million children under 5 years of age die annually in the Third World, mainly due to diarrhoea, pneumonia, malaria and immunizable diseases. The problems of poverty, malnutrition, poor sanitation, illiteracy and high fertility that traditionally are associated with underdevelopment are now being compounded by social disruption due to rapid changes in lifestyle, new diseases such as AIDS and Third World debt. A vital part of the solution is provision of basic medical and education services to all, with emphasis on female literacy and improving the status of women. Key elements in providing basic medical services are delegation and empowerment. Doctors must delegate the delivery of essential child health services to appropriately trained and adequately supported auxiliaries. Parents, especially mothers, need to be empowered with the knowledge and resources to recognize and manage, or assist in the management of, their children's health problems.     

Evaluation of engraftment syndrome in children following full‐matched related donor hematopoietic stem cell transplantations

The term “ES” has been widely used for describing a clinical condition consisting of skin rash, fever, and weight gain that occur during neutrophil recovery period following HSCT. In this study, the incidence, clinical features, risk factors, and outcomes of ES were evaluated in 169 children following allogeneic HSCT from full‐matched related donor according to the Spitzer criteria. Seventeen patients (10.1%) presented with clinical conditions suggesting ES. In both univariate and multivariate analysis underlying malignant disease and early release of monocytes to the PB, and in univariate analysis using only CsA for GVHD prophylaxis were found to be the significant risk factors for the development of ES. Patients with ES experienced significantly higher incidence of acute and chronic GVHD and propensity toward a higher rate of TRM. OS did not differ between the patient groups. Thirteen of 17 patients received steroid therapy, and all but one patient responded to therapy. Monitoring for early detection of ES and early intervention with steroid therapy is the key for recovery. The most crucial approach for this purpose mainly is to find out and use the most useful and feasible diagnostic criteria for routine medical practice.