Hematopoietic stem cell transplantation with a reduced‐intensity conditioning regimen in pediatric patients with Griscelli syndrome type 2

Partial albinism with variable immunodeficiency are the two major characteristics of Griscelli syndrome type 2 (GS‐2). This syndrome is usually associated with a high mortality rate and commonly results in early childhood death. Patients suffer from different infections and experience crisis of HLH. HSCT remains the sole curative treatment for GS‐2. We prospectively analyzed the outcomes of transplantation with RIC regimen in five patients. The median age at transplantation was 21.6 months (range: 12–30). All of the patients underwent HSCT from HLA‐matched related donors. Currently, four patients are cured, and symptoms of recurrent infections and HLH crisis are not seen in them. The only patient who died had undergone HSCT in the accelerated phase of HLH. One patient who developed acute GvHD had a favorable response to therapy. No chronic GvHD occurred in patients. It seems that the use of RIC regimen as a method of transplant preparation is effective and tolerable in this group of patients with various comorbidities. It is recommended to carry out HSCT in these patients at lower ages, before presentations of different infections and HLH crisis.     

Successful cord blood transplantation using a reduced‐intensity conditioning regimen for advanced childhood‐onset cerebral adrenoleukodystrophy

Awaya T, Kato T, Niwa A, Hiramatsu H, Umeda K, Watanabe K‐i, Shibata M, Yamanaka Y, Maruya E, Saji H, Nakahata T, Adachi S. Successful cord blood transplantation using a reduced‐intensity conditioning regimen for advanced childhood‐onset cerebral adrenoleukodystrophy.
Pediatr Transplantation 2011: 15: E116–E120. © 2009 John Wiley & Sons A/S. Abstract: The CCALD, which is caused by a mutation of the ABCD1 gene that encodes a peroxisomal membrane protein, progresses to a stage where the patient is in a vegetative state and can cause death within 3–5 yr after the appearance of neurological symptoms. Although HSCT is the only means of preventing the progression of this disease, HSCT is currently recommended only for cases diagnosed in the early stages. Previous reports on HSCT in advanced CCALD have indicated that the complications of the HSCT procedure seem to outweigh its benefits with respect to survival and neurological outcome. In this case, we successfully treated advanced CCALD with CBT using a reduced‐intensity conditioning regimen to reduce regimen‐related toxicity and transplant‐associated morbidity and mortality. Neither neurological deterioration nor deterioration of MRI abnormalities were observed during the clinical course. We report that CBT using the reduced‐intensity conditioning regimen was well tolerated, stopped disease progression and contributed to a good neuropsychological outcome in this case of advanced CCALD.     

Successful treatment of idiopathic colitis related to XIAP deficiency with allo‐HSCT using reduced‐intensity conditioning

Recently, it has been reported that Crohn's‐like intractable colitis occurred in approximately 20% of the patients with XIAP deficiency, also known as X‐linked lymphoproliferative disease type 2. Because treatment used for Crohn's disease is not always effective for Crohn's‐like colitis related to XIAP deficiency, more effective treatment should be established. Although several studies reported allo‐HSCT might be promising even for Crohn's‐like colitis related to XIAP deficiency, the outcome of allo‐HSCT using MAC for XIAP deficiency is extremely poor due to frequent TRM. In addition, there is little information about the outcome of allo‐HSCT for intractable colitis related to XIAP deficiency. Herein, we describe a patient with intractable colitis related to XIAP deficiency who was successfully treated with allo‐HSCT using a reduced‐intensity conditioning regimen. Although allo‐HSCT using the RIC regimen might be a curative therapeutic option for intractable colitis with XIAP deficiency, the prognostic factors that will determine the success of allo‐HSCT require further clinical information of more patients.     

A single‐center experience using alemtuzumab,fludarabine, melphalan,and thiotepa as conditioning for transplantation in pediatric patients with chronic granulomatous disease

Chronic granulomatous disease (CGD) is an immune deficiency characterized by defective neutrophil function and increased risk of life‐threatening infections. Allogeneic hematopoietic cell transplantation is curative for CGD, and conditioning regimen impacts transplant‐related outcomes. We report a single‐center prospective study (NCT01821781) of four patients with CGD transplanted using a reduced‐intensity conditioning regimen (RIC) containing alemtuzumab, fludarabine, melphalan, and thiotepa. Patients had early immune reconstitution with low incidence of infections. Disease‐free survival was 75% at a median of five years after transplant. This RIC regimen presents an alternative approach for transplant of patients with CGD who may not tolerate busulfan‐based conditioning.     

Successful use of reduced‐intensity conditioning and matched‐unrelated hematopoietic stem cell transplant in a child with Diamond‐Blackfan anemia and cirrhosis

For patients with DBA who are transfusion dependent, HSCT is the only cure. Chronic transfusions can lead to cirrhosis secondary to iron overload, making them poor candidates for myeloablative HSCT. RIC regimens are associated with lower morbidity and mortality compared to myeloablative regimens, but use of RIC in DBA has been limited. Here we present a 14‐yr‐old girl with DBA and multiple comorbidities including liver cirrhosis, who underwent MUD HSCT utilizing a RIC regimen that is novel to this condition. She tolerated the regimen well, and at 21 months, she remains transfusion independent with chimerisms at 99%.     

Successful treatment of relapsed anaplastic large cell lymphoma with vinblastine monotherapy and allo‐HSCT with reduced intensity conditioning regimen

Relapsed anaplastic large cell lymphoma (ALCL) is chemosensitive, but recurrence is common. Although vinblastine (VLB) monotherapy is an effective treatment for relapsed ALCL, the optimal treatment duration is unknown, and some patients experience further relapse after completing the treatment. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is also an effective treatment for relapsed ALCL, although transplant‐related toxicity is a problem. Here, we report an 11‐year‐old patient with relapsed ALCL who underwent induction therapy with VLB monotherapy and achieved complete remission (CR) after 12 courses. CR was confirmed on positron emission tomography–computed tomography. The patient then underwent allo‐HSCT with reduced intensity conditioning (fludarabine, melphalan, and low‐dose total body irradiation). He developed grade II acute graft‐versus‐host disease (GVHD), which was successfully treated with methylprednisolone. There was no evidence of chronic GVHD. He has remained in CR without any complications for 19 months after allo‐HSCT.     

Successful allogeneic stem cell transplantation with a reduced‐intensity conditioning in a leukocyte adhesion deficiency type I patient

Hamidieh AA, Pourpak Z, Alimoghaddam K, Movahedi M, Bahoush G, Behmanesh F, Moin M, Ghavamzadeh A. Successful allogeneic stem cell transplantation with a reduced‐intensity conditioning in a leukocyte adhesion deficiency type I patient.
Pediatr Transplantation 2011: 15:E30–E33. © 2009 John Wiley & Sons A/S. Abstract: LAD‐I is a rare, autosomal recessive, primary immunodeficiency in which phagocyte adhesion and chemotaxis are impaired. Multiple infections in the absence of pus accumulation and persistent elevated peripheral blood neutrophil counts are the hallmark of LAD‐I. Allogeneic HSCT is the only treatment proved to be potentially curative for phagocyte adhesion impairment in LAD‐I. Here, we report on a case of a 30‐month‐old girl with LAD‐I, in whom peripheral blood stem cell from a genotypically identical sibling resulted in mixed chimerism.     

Impact of melphalan dose during reduced‐intensity conditioning on engraftment of cord blood transplantation for chronic Epstein‐Barr virus‐associated T or NK cell lymphoproliferative diseases

The rejection rate in cord blood transplants for chronic Epstein‐Bar virus‐associated T or natural killer cell lymphoproliferative diseases using our standard reduced‐intensity conditioning “LPAM140 regimen,” which includes fludarabine, melphalan (LPAM), etoposide, and antithymocyte globulin, has been high. To ensure better engraftment, we increased the LPAM dose to 210 mg/m² (“LPAM210 regimen”). Patient data (n = 22; LPAM140, n = 7; LPAM210, n = 15) were analyzed retrospectively. The engraftment rate after the LPAM210 regimen (100.0%) was significantly higher than that after the LPAM140 regimen (57.1%; P = .002). Fludarabine combined with melphalan (210 mg/m²) had a favorable impact on engraftment.     

Fludarabine based reduced intensity conditioning regimens in children undergoing allogeneic stem cell transplantation for severe aplastic anemia

Fourteen children with a median age of 9.8 yr with SAA (10 males, four females) underwent related HLA identical allogeneic stem cell transplantation using Flu, Cy +/- ATG between 2004 and 2006. GVHD prophylaxis consisted of cyclosporine +/- mini methotrexate. Graft source included PBSCs (seven) or BM (seven). One patient expired <7 days post-transplant, while 12 (85.7%) patients engrafted with median neutrophil and platelet engraftment times of 13.8 and 14.5 days each. One patient had primary graft failure and expired on Day +27. Acute GVHD was seen in 25% of evaluable patients while limited chronic GVHD was seen in 33%. At a mean follow-up of 18 months, 12 patients (85.7%) are alive and well. Compared with a historical cohort of 12 children transplanted using Cy/ATG, there was faster engraftment (13.8 vs. 16.4 days; p = 0.002) with lower rejection rates (7.1 vs. 36.3%; p = 0.133) and improved event free (85.7 vs. 54.5%; p = 0.177) and overall survival (85.7 vs. 63.6%; p = 0.350). Flu with Cy +/- ATG reduces rejection and improves overall and event free survival in children with aplastic anemia.     

Successful unrelated cord blood transplantation for chronic granulomatous disease: a case report and review of the literature

Abstract:  CGD is a rare inherited immunodeficiency disorder that is caused by disability of oxidative killing. We presented a two-yr-old boy with CGD who was suffering from multiple systemic abscesses. He received the first BMT from his HLA-haploidentical mother after conditioning with Flu, melphalan, and ATG. Although the maximum of 42% donor chimerism was achieved, it disappeared 73 days after the BMT. Then, we performed 5/6-matched unrelated cord blood re-transplantation after conditioning with Flu, Bu, and TBI (2 Gy). Engraftment and complete donor chimerism were achieved on days 18 and 19, respectively. The patient is now free from infection and maintains complete donor chimerism without GVHD 36 months after the cord blood re-transplantation. We postulate that the unrelated CBT has a potential to be an alternative strategy and might be beneficial for patients with CGD who do not have an HLA-identical donor.     

Successful treatment of post‐transplant thrombocytopenia with romiplostim in a pediatric patient with X‐linked chronic granulomatous disease

Thrombocytopenia is a frequent complication following HSCT in pediatric patients. Romiplostim is a TPO receptor agonist that has been utilized successfully in the treatment of pediatric patients with immune thrombocytopenia. We describe a three‐yr‐old male with X‐linked CGD treated with an unrelated donor bone marrow transplant. His course was complicated by the development of symptomatic thrombocytopenia. He was started on romiplostim with prompt improvement in his thrombocytopenia. We found the use of romiplostim to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of immunosuppressive agents such as corticosteroids.     

Successful treatment of refractory Langerhans cell histiocytosis with pulmonary aspergillosis by reduced‐intensity conditioning cord blood transplantation

Hatakeyama N, Hori T, Yamamoto M, Inazawa N, Hirako Y, Tsutsumi H, Suzuki N. Successful treatment of refractory Langerhans cell histiocytosis with pulmonary aspergillosis by reduced‐intensity conditioning cord blood transplantation.
Pediatr Transplantation 2010: 14: E4–E10. © 2009 Wiley Periodicals, Inc. Abstract: The prognosis of multisystem LCH in children with risk organ involvement is extremely poor when they fail to respond to conventional chemotherapy. In such patients, allogeneic SCT may produce complete and sustained remission; however, high‐dose myeloablative regimens are frequently associated with treatment‐related morbidity and mortality. More recently, allogeneic SCT following an RIC regimen has been performed as an alternative salvage approach. We describe a nine‐month‐old boy with refractory multisystem LCH with pulmonary aspergillosis who was successfully treated with reduced‐intensity cord blood transplantation.     

Successful reduced‐intensity conditioning hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria with aplastic anemia in two children

Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare cause of bone marrow failure in children. We report two children who presented with pancytopenia, and were diagnosed with PNH with severe aplastic anemia. Both children underwent upfront, successful hematopoietic stem cell transplantation with reduced‐intensity conditioning. One patient had a syngeneic donor, and one patient had a 10/10 matched unrelated donor. Neither patient developed graft versus host disease, infections, or recurrent PNH. Reduced‐intensity conditioning hematopoietic stem cell transplantation is a reasonable therapy for PNH with marrow failure in children.     

儿童慢性肉芽肿病的诊治进展

慢性肉芽肿病是一种因NADPH氧化酶功能障碍引起的原发性免疫缺陷病,在临床较为少见,病死率较高.典型的临床表现为儿童早期反复致命感染.慢性炎症持续存在导致局部形成肉芽肿,易引起局部梗阻.针对慢性肉芽肿病较特异的诊断方法包括:四氮唑蓝还原试验、二氢罗丹明流式细胞分析方法和基因序列分析等.目前造血干细胞移植是大多数慢性肉芽肿病治疗手段,但应选择合适的移植时机,以提高移植成功率并减少并发症.基因治疗慢性肉芽肿病长期的有效性和安全性还有待进一步深入研究.该文就近年来慢性肉芽肿病的发病机制、早期诊断技术和治疗等方面的研究进展作一综述.