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.     

Reduced-intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita

DC is an inherited bone marrow failure syndrome mainly characterized by nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. Bone marrow failure is the most common cause of death in patients with DC. Because previous results of HSCT with a myeloablative regimen were disappointing, we used a reduced-intensity conditioning regimen for two patients with classic DC, and one patient with cryptic DC who harbored the TERT mutation. Graft sources included two mismatched-related bone marrow (BM) donors and one unrelated BM donor. Successful engraftment was achieved with few regimen-related toxicities in all patients. They were alive 10, 66, and 72 months after transplantation, respectively. Long-term follow-up is crucial to determine the late effects of our conditioning regimen.     

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.     

Iodine-131-metaiodobenzylguanidine therapy with reduced-intensity allogeneic stem cell transplantation in recurrent neuroblastoma

Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stem cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.     

Engraftment syndrome following allogeneic hematopoietic stem cell transplantation in children

Abstract:  ES is a complication that occurs immediately before or at the timing of neutrophil engraftment following autologous or allogeneic SCT. It is characterized by fever, skin rash, and non-cardiac pulmonary infiltrates. We evaluated the incidence, risk factors, and outcomes of ES following allogeneic SCT in children. Of 100 pediatric patients, 20 (20%) developed ES occurring at a median of 14 days (range 8–27 days) post-transplant. Patients presented with fever (100%), skin rash (100%), diffuse pulmonary infiltration (25%), and body weight gain (85%). On multivariate analysis, significant risk factors for ES included younger age (<8 yr old) and human leukocyte antigen disparity between donors and recipients. Univariate analysis showed that patients with ES had a higher incidence of developing chronic graft-versus-host disease and ES was not associated with other complications. Event-free survival did not significantly differ between patients with and without ES regardless of the presence of malignant or non-malignant diseases.     

Long-term graft-versus-tumor effect following reduced intensity hematopoietic stem cell transplantation in a child with metastatic renal cell carcinoma

Pediatric renal cell carcinoma (RCC) is rare and different from adult RCC. Although target agents have recently been introduced, allogeneic hematopoietic stem cell transplantation exploiting graft-versus-tumor effect still remains an important treatment option for metastatic RCC. A 2-year-old male with RCC developed hepatic metastases 6 months following radical nephrectomy and subsequent cytokine therapy. Allogeneic reduced-intensity stem cell transplantation (RIST) with early withdrawal of immunosuppression and delayed donor lymphocyte infusions was performed. A second transplantation was undertaken following marrow aplasia. Now he remains progression-free with regression of hepatic metastases 5.7 years after RIST, along with complete donor chimerism.     

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.     

异基因造血干细胞移植治疗儿童再生障碍性贫血临床分析

目的探讨异基因造血干细胞移植在儿童再生障碍性贫血治疗中的作用。方法10例再障患儿中,5例行HLA相合同胞供者异基因外周造血干细胞移植,3例行无关供者异基因外周造血干细胞移植,1例行无关供者骨髓移植,1例行脐血移植。结果1例接受脐血移植者未植活,其余9例均植入。中位植入时间14d（8～24d）,中性粒细胞〉0.5×10^9/L中位时间12d（8～19d）,血小板〉20×10^9/L中位时间17d（9～40d）。2例发生排斥,1例接受了第二次移植,1例移植后3个月血象开始自行恢复。结论如有HLA相合的同胞供者,异基因造血干细胞移植可作为儿童再障的一线治疗;临床重症感染无法控制的患儿,并非移植绝对反指征,相反可通过移植后的造血重建控制感染。     

Visual perceptual skills and visual motor integration in children and adolescents after allogeneic hematopoietic stem cell transplantation

The aim of the study was to study visual acuity, visual perceptual, and VMI skills in patients after HSCT in childhood. Tests of visual perceptual skills, VMI, and visual acuity were performed in 102 children/adolescents (age range 4.3‐20.9 years). Mean time from HSCT to testing was 6.0 years (0.9‐17.5 years). Visual acuity was median 1.0 decimal (range 0.16‐1.6). Visual perceptual skills (memory, form constancy, visual sequential memory) and VMI were low compared to age‐equivalent normative data with, respectively, 36%, 45%, 60%, and 46% of all patients performing below the 25 percentile. All patients performed significantly lower than the 50 percentile in the reference material in visual sequential memory, P < .001 (boys P < .001 and girls P < .05). All patients also performed significantly lower than the 50 percentile in VMI (P < .01) (boys P < .05). Pretransplant conditioning regimen did not affect outcome if the results were corrected for age at HSCT. Visual perceptual skill problems and VMI problems frequently occur in patients after HSCT in childhood. Age at HSCT and original diagnosis influence the outcome. Neuropsychological assessment including visual perception is recommended in children after HSCT.     

The expanding applications of non-myeloablative stem cell transplantation

Abstract:  Non-myeloablative preparative strategies for allogeneic stem cell transplantation (SCT) have been increasingly utilized for a variety of hematological malignancies, solid tumours, and for tolerance induction. These regimens are associated with less transplant-related morbidity and mortality than conventional transplant conditioning regimens. It is not yet clear whether graft-vs.-host disease (GVHD) protection is afforded. Potent antitumour responses have been described in a variety of advanced malignancies. We have utilized a cyclophosphamide/anti-T-cell antibody therapy approach, which has resulted in the uniform induction of mixed chimerism. In many cases, this has served as an immunological platform for adoptive cellular immunotherapy (via donor leukocyte infusions). The results of this experience, as well as the outcomes of non-myeloablative stem cell transplantation (NST) for other malignant and nonmalignant conditions are described.     

Non-myeloablative transplantation for severe congenital neutropenia

Severe Congenital Neutropenia is a rare condition characterized by a very low neutrophil count, which pre-disposes the affected child to recurrent bacterial infections. Treatment with granulocyte colony stimulating factor (G-CSF) has dramatically improved the prognosis of these children; but in patients who have become G-CSF refractory, hematopoeitic stem cell transplant is still the only effective curative treatment. We describe a patient who was unresponsive to escalating doses of G-CSF and underwent a successful reduced intensity conditioning, matched unrelated donor allograft resulting in cure.     

Successful outcome of allogeneic stem cell transplantation in Seckel syndrome

Seckel syndrome is a rare autosomal recessive disease, genetically heterogeneous, characterized by short stature, prenatal microcephaly, intellectual disability, dysmorphic features, chromosomal instability, and hematological disorders. We report the case of a six‐yr‐old boy with Seckel syndrome and aplastic anemia who underwent successful allogeneic bone marrow transplantation from ten of ten HLA matched unrelated donor. Currently the patient is on D+771, in good health conditions and with no further complications. In conclusion, this case indicates that bone marrow transplantation is an acceptable therapeutic option for Seckel syndrome complicated by hematological alterations.