Antiviral therapy for cytomegalovirus infections in pediatric patients

Appreciation of the spectrum of illness caused by cytomegalovirus (CMV) infections has increased markedly during the past 2 decades. The number of immunosuppressed patients also has increased during the same time period, reflecting the central tenet that CMV disease is most severe in this patient population. Fortunately, antiviral therapies with activity against CMV also have been identified during this same time course, and they include ganciclovir, foscamet, and cidofovir. Although all 3 of these therapies can have significant toxicities associated with them, nonetheless they are employed with relative frequency to treat potentially life-threatening CMV disease. Ganciclovir is the first-line compound used, followed by foscarnet and cidofovir. This article summarizes those CMV infections that require antiviral therapy and outlines therapeutic options for each.     

Cytomegalovirus reactivation in pediatric hemopoietic progenitors transplant: a retrospective study on the risk factors and the efficacy of treatment

Cytomegalovirus (CMV) disease is an important infectious complication after allogeneic hemopoietic progenitors transplant (HPT), but few data are available in children. To investigate the factors influencing CMV reactivation, subsequent relapses of positive antigenemia, and the development of organ disease in children, the authors retrospectively analyzed 108 children who received allogeneic HPT for malignant conditions at one center. Of these, 41 were CMV serology positive (donor or recipient) before HPT. All those with CMV-positive serology received high-dose acyclovir in conjunction with weekly CMV phosphoprotein-pp65 antigen monitoring of the peripheral blood during the first 3 months. Those with CMV reactivation (positive antigenemia) received preemptive treatment with ganciclovir and/or foscarnet to prevent CMV disease. The incidence of positive antigenemia in this cohort was 41.5% at a mean of 44 +/- 31.6 days after HPT. Two patients (4.9%) subsequently developed late CMV disease. Recipient CMV status was significantly (P = 0.0001) more relevant to reactivation than donor status. Reactivations were significantly more common in single recipient seropositive than double (donor and recipient) positive pairs (P = 0.05). Reactivations were significantly more common in recipients of unrelated donor grafts than matched-related donor grafts (P = 0.025). Reactivations also occurred significantly more in T-cell-depleted graft recipients (P = 0.004) than recipients of unmanipulated grafts. The subsequent development of disease was more common in a CMV-seropositive recipient receiving a CMV-seronegative, T-cell-depleted, unrelated donor graft, and after transplantation receiving treatment for acute graft-versus-host disease. Patients with identified high risk factors for CMV reactivation and disease should be monitored by CMV PCR, and early preemptive treatment should be instigated to prevent the development of disease.     

Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: An analysis of 18 Japanese cases

Oshima K, Hanada R, Kobayashi R, Kato K, Nagatoshi Y, Tabuchi K, Kato S; for the Hematopoietic Stem Cell Transplantation Committee of the Japanese Society of Pediatric Hematology. Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: An analysis of 18 Japanese cases.
Pediatr Transplantation 2010: 14:657–663. © 2010 John Wiley & Sons A/S. Abstract: We studied the outcome of allogeneic HSCT in patients with SCN. Between 1989 and 2005, 18 patients with SCN in Japan received HSCT for reasons other than malignant transformation, i.e., because of the lack of or a partial response to treatment with r‐HuG‐CSF. The median age of the patients at the first HSCT was three and a half yr (range 0.2–16.7 yr). Nine patients received stem cells from an HLA‐identical sibling donor and nine from an alternative donor. Twelve and six patients received myeloablative and non‐myeloablative conditioning regimens, respectively. Engraftment occurred at the first HSCT in 12 patients, four patients received a second HSCT for graft failure, and two patients died. The cause of death was renal failure and graft failure at the first and second HSCT, respectively. The cumulative incidence of grade II–IV acute GVHD and TRM at the first transplantation was 11% and 5.6%, respectively. Of our patients, 16 are alive and in complete remission, with a median follow‐up of six and a half yr. Our results suggest that HSCT is beneficial for patients with SCN refractory to r‐HuG‐CSF treatment.     

Liver transplantation in a child with liver failure due to chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from the same unrelated living donor

Englert C, Ganschow R. Liver transplantation in a child with liver failure due to chronic graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation from the same unrelated living donor. Abstract: We report a case of a six‐yr‐old boy who developed chronic GVHD of the liver, intestines, and skin following allogeneic hematopoietic SCT. The boy received an allogeneic hematopoietic stem cell transplant at the age of two yr because of early recurrence of ALL. Chimerism analysis showed complete chimerism. In the following year, he developed GVHD despite adequate immunosuppressive therapy. Liver biopsy showed liver GVHD resulting in liver cirrhosis by the age of five yr. LTx was performed with a left liver lobe from the unrelated donor from whom the stem cells had been taken. Immunosuppressive therapy consisted of low‐dose steroids and low‐dose cyclosporine. The postoperative course was uneventful. Graft function was excellent, and we performed protocol biopsies at seven days and three wk as well as three, six, and nine months after transplantation; none of these showed any signs of rejection or GVHD. Immunosuppressive therapy was discontinued nine months after LTx. Three yr after transplantation, the boy is in good condition with normal graft function. To our knowledge, this is the first report on LTx following allogeneic hematopoietic SCT from the same unrelated living donor.     

Unrelated CD3/CD19-Depleted Peripheral Stem Cell Transplantation for Hurler Syndrome

For patients with mucopolysaccharidosis type IH (MPS1-H; Hurler syndrome), early allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice. One boy and one girl aged 20.5 and 22 months, respectively, with MPS1-H received a conditioning regimen consisting of thiotepa, fludarabine, treosulfan, and ATG. Grafts were peripheral blood stem cells from unrelated donors (10/12 and 11/11 matched), that were manipulated by CD3/CD19 depletion and contained 20.3 and 28.2 × 10⁶ CD34+ cells/kg body weight, respectively. Both patients achieved stable hematopoietic engraftment and stable donor chimerism. Neither acute or chronic graft-versus-host disease (GVHD) nor other severe transplant-related complications occurred. At a follow-up of 48 and 37 months, both patients are alive and well with normal levels of α-L-iduronidase and have made major neurodevelopmental progress. Treosulfan-based conditioning offers the advantage of reduced toxicity; the use of unrelated CD3/CD19-depleted peripheral stem cell grafts allows transfusion of high CD34+ cell numbers together with a “tailored” number of CD3+ cells as well as engraftment facilitating cells in order to achieve rapid hematopoietic engraftment while reducing the risk of graft rejection and GVHD. This regimen might be an additional option when unrelated donor HSCT is considered for a patient with MPS1-H.     

儿童造血干细胞移植后巨细胞病毒感染的临床研究

目的了解儿童造血干细胞移植后巨细胞病毒的感染率和防治方法。方法对从2001年8月到2007年3月北京儿童医院血液病中心37例作造血干细胞移植的血液肿瘤及先天遗传性疾病患儿进行回顾性分析。结果31例可研究病例中,5例自体造血干细胞移植及5例同基因造血干细胞移植患儿无人类巨细胞病毒（HCMV）感染,21例异基因造血干细胞移植患儿,发生HCMV感染7例,感染率为33.3%,大剂量阿昔洛韦加丙种球蛋白预防及早期更昔洛韦加大剂量静脉丙种球蛋白治疗,仅1例发生巨细胞病毒相关性间质性肺炎（CMV-IP）,无1例发生巨细胞病毒感染相关死亡。结论巨细胞病毒感染是儿童造血干细胞移植术后的主要并发症,临床上进行定期监测、前瞻性预防、早期诊断和及时合理治疗,对降低移植术后巨细胞病毒感染和提高移植成功率至关重要。     

Multiple viral infections post‐hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts

Olkinuora HA, Taskinen MH, Saarinen‐Pihkala UM, Vettenranta KK. Multiple viral infections post‐hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts.
Pediatr Transplantation 2010:14:242–248. © 2009 John Wiley & Sons A/S. Abstract: Delayed immune reconstitution and the ensuing opportunistic infections among children following hematopoietic stem cell transplantation (HSCT) are associated with increased treatment‐related morbidity and mortality (TRM). We retrospectively evaluated the impact of viral infections on the posttransplant recovery of pediatric recipients of stem cell grafts as a reflection of their posttransplant immunoreconstitution in a single institution setting. The case histories of 124 children (during 1/1999‐9/2006) were reviewed for infectious episodes, and correlated with their respective clinical parameters. Patients with a high risk for CMV received prophylaxis, but failures in the prophylaxis were common (40%). 110/124 (89%) of these allogeneic patients had at least one viral reactivation/clinical infection posttransplant. In this group of pediatric patients chronic GVHD (P<0,001) and secondary graft failure were significantly (P=0,001) associated with early (during the first 100 days post HSCT), multiple (≥ 2) viral infections. Our data indicate that viruses are common pathogens among pediatric recipients of allogeneic stem cell grafts. In this group of patients multiple viral infections early on seem to reflect an even more severe degree of immunological derangement in the recipient and identify a group of patients with an increased risk of chronic GVHD and secondary graft failure.     

Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia

EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT.     

Hematopoietic stem cell transplantation for Diamond-Blackfan anemia: a report from the Aplastic Anemia Committee of the Japanese Society of Pediatric Hematology

Transfusion-dependent Diamond-Blackfan anemia (DBA) patients opt for allogeneic hematopoietic stem cell transplantation (HSCT) as curative therapy. Clinical outcomes of 19 transplanted Japanese patients were analyzed. Prior to HSCT, 10 patients (53%) suffered hemosiderosis with organ dysfunction, and all eight with short stature (42%) had adverse effects of prednisolone. Median age at the time of HSCT was 56 months. Transplantation sources were 13 bone marrow [six human leukocyte antigen (HLA)-matched siblings, and six HLA-matched and one HLA-mismatched unrelated donors], five cord blood (two HLA-matched siblings and three HLA-mismatched unrelated donors), and one peripheral blood from haploidentical mother. All 13 patients with bone marrow transplantation (BMT) and two with sibling cord blood transplantation (CBT) had successful engraftment. Of three patients who underwent unrelated CBT, one died after engraftment, and the other two had graft failure but succeeded in a second BMT from an HLA-disparate father and unrelated donor, respectively. One died shortly after haploidentical PBSCT. The five-yr failure-free survival rate after BMT was higher than CBT (100%: 40%, p=0.002). Platelet recovery was slower in seven unrelated BMT than in six sibling BMT (p=0.030). No other factors were associated with engraftment and survival. These results suggest that allogeneic BMT, but not unrelated CBT, is an effective HSCT for refractory DBA.     

ABO incompatible stem cell transplantation in children does not influence outcome

BACKGROUND: Although delayed red cell engraftment and/or hemolysis have been thoroughly documented in association with ABO incompatibility between donor and recipient in patients undergoing hematopoietic stem cell transplantation (HSCT), there are no studies defining the general, long term clinical outcome in a large group of pediatric patients. METHODS: We undertook a retrospective single center analysis of children undergoing pediatric allogeneic stem cell transplantation to determine the influence of ABO donor/recipient incompatibility. Outcome was analyzed according to donor type and included survival, graft versus host disease (GvHD), relapse, days of infection, antibiotic use, transfusion requirement and duration of hospital stay. RESULTS: Two hundred and sixteen children (136 males; 80 females, aged 0-19) transplanted between January 1992 and December 2003 were included in the study. Indications for transplantation were hematological malignancies (n=179) and aplastic conditions (n=37). ABO compatibility was documented in 121 donor/recipient pairs. ABO incompatibility was documented in 95 donor/recipient pairs with 40 major, 40 minor and 15 bi-directional incompatible pairs. ABO incompatibility did not influence survival rate (P=0.3762), the incidence of GvHD (P=0.253) or rate of relapse (P=0.930). Recovery of leucocytes was influenced by ABO incompatibility (P=0.0493), but the rate of infection, transfusion requirements and duration of hospital stay are not. CONCLUSION: In the pediatric setting, ABO major and/or minor mismatch between donor and recipient did not significantly influence the outcome of HSCT. The choice of donor should be determined by the degree of HLA match and CMV status in preference to ABO blood group compatibility.     

儿童第二次非血缘供者造血干细胞移植2例

目的探索非血缘造血干细胞移植后复发病例进行第二次移植的可行性。方法患幼年型慢性粒单细胞性白血病(JMML)及重型β-地中海贫血的两例患儿接受非血缘供者造血干细胞移植后分别于移植后的10个月和1个月后原疾病复发,前者给予福达华加环磷酰胺预处理后输注原供者干细胞,降低预防移植物抗宿主病强度;后者给予含TBI预处理,移植另一非血缘供者外周血干细胞。结果两例患者第二次移植后均获得稳定植入,JMML患者并发急慢性移植物抗宿主病,完全缓解至+24月;地中海贫血患者已完全脱离输血状态至+23月。结论对于非血缘造血干细胞移植后复发的患儿,第二次非血缘供者造血干细胞移植是可行的。     

脐带血异基因造血干细胞移植后噬血细胞性淋巴组织细胞增生症1例临床分析

目的探讨异基因造血干细胞移植后噬血细胞性淋巴组织细胞增生症(HLH)的临床特征、诊断及治疗。方法回顾性分析1例急性髓系白血病非血缘相关脐带血造血干细胞移植(AML-URD-UCBT)患儿术后并发HLH的临床特点并复习相关文献。结果患儿移植术后第6天(+6 d,下同)出现皮肤、肝脏、肠道急性移植物抗宿主病(aGVHD),先后给予糖皮质激素、环孢素A(CsA)、赛尼哌、霉酚酸酯(MMF)、他克莫司(FK506)等免疫抑制治疗后,aGVHD症状好转,但+26 d后出现活动性巨细胞病毒(CMV)感染合并HLH,给予静脉注射用丙种球蛋白、无环鸟苷、更昔洛韦抗CMV治疗,输红细胞、血小板、血浆、纤维蛋白原等支持治疗,参照HLH-2004方案予依托泊苷、糖皮质激素及CsA治疗后,+61 d检测血CMV早期/晚期基质蛋白(CMV-PP65)转阴,+55、+63 d骨髓象未见噬血细胞,呈HLH完全缓解骨髓象,临床症状及血常规等实验室指标好转;+83 d检测血CMV-PP65及CMV脱氧核糖核酸(CMV-DNA)转阳,+86 d因严重肺部感染、肺出血、消化道出血及多器官功能衰竭而死亡。结论异基因造血干细胞移植后aGVHD及抗aGVHD的免疫抑制治疗,是引起移植后CMV感染相关HLH的危险因素;HLH-2004方案未考虑到异基因造血干细胞移植后HLH的特殊性,需进一步研究有针对性的治疗方案,以提高疗效。     

Cytomegalovirus (CMV) infections in children undergoing hematopoetic stem cell transplantation

Cytomegalovirus (CMV) is one of the major causes of morbidity and mortality after hematopoetic stem cell transplantations (HSCT). The purpose of the study was to analyze risk factors of CMV disease in children undergoing HSCT. A total of 110 children who undergone hematopoetic stem cells transplantation were analyzed. In 16 patients (14.5%) CMV antigenemia in white blood cells was diagnosed. Most patients with CMV infection had undergone alloHSCT; one patient had undergone autologous transplantation. Second CMV reactivation in 4 of 16 patients was observed. Acute GvHD occurred in 11/15 patients. Early onset of CMV infection in 13/16 patients and late onset in 3/16 patients were diagnosed. CMV serological status of the donor and recipient before transplantation in children with CMV antigenemia was analyzed. The risk factors of CMV infection in analyzed group of children were type of transplant, recipient seropositivity before transplantation, and presence and intensity of GvHD. In most cases reactivation of CMV infection was diagnosed. CMV infection can also occur in the late post-transplantation period. CMV reactivation can occur in patients after autologous HSCT.     

A pilot phase II study of alternate day ganciclovir and foscarnet in preventing cytomegalovirus (CMV) infections in at-risk pediatric and adolescent allogeneic stem cell transplant recipients

BACKGROUND: Prophylaxis with ganciclovir or foscarnet post allogeneic stem cell transplant (AlloSCT) reduces cytomegalovirus (CMV) disease. Combination ganciclovir/foscarnet is more effective than monotherapy in HIV patients with CMV retinitis. We hypothesized that alternate day ganciclovir and foscarnet for the prevention of CMV during the first 100 days after AlloSCT would be safe and effective. PROCEDURE: Fifty-three pediatric and adolescent AlloSCT recipients receiving 57 AlloSCTs where donors and/or recipients were CMV seropositive received ganciclovir (5 mg/kg/48 hr) alternating with foscarnet (90 mg/kg/48 hr) from myeloid recovery (>or=ANC 750/mm3) until Day +100. RESULTS: Patients were: M:F 31:22; age 6 years (0.8-18 years); donor sources: 25 related peripheral blood/bone marrow, 3 unrelated adult peripheral blood, 26 unrelated cord blood, and 3 related cord blood. GVHD prophylaxis included tacrolimus/mycophenolate mofetil (MMF). Median-nucleated and CD34 cell counts were 7.3x10(8)/kg and 5.07x10(6)/kg, respectively, for BM/PBSC; 4.07x10(7)/kg and 1.69x10(5)/kg, respectively, for CB. Despite a 36.5% probability of Grades II-IV acute GVHD, no patient developed systemic CMV disease. Five percent had Grade IV hematological toxicity that required discontinuation of ganciclovir. Twenty-five percent required discontinuation of foscarnet secondary to electrolyte abnormalities and/or renal dysfunction that were presumed to be multifactorial in origin. Probability of 1-year overall survival was 58.8%. CONCLUSIONS: Alternate day ganciclovir/foscarnet in AlloSCT recipients where recipient and/or donor is seropositive appears to be tolerable and 100% effective in preventing CMV systemic disease. A randomized study will be required to determine if this approach is superior to other CMV prophylactic designs.     

Leflunomide therapy for BK virus allograft nephropathy in pediatric and young adult kidney transplant recipients

Araya CE, Garin EH, Neiberger RE, Dharnidharka VR. Leflunomide therapy for BK virus allograft nephropathy in pediatric and young adult kidney transplant recipients.
Pediatr Transplantation 2010: 14: 145–150. © 2009 Wiley Periodicals, Inc.
Abstract:  BKVAN affects about 5% of kidney transplant recipients and may lead to graft failure. Treatment for BKVAN is challenging. Leflunomide, an immunosuppressant with antiviral activity in vitro was used successfully in some adult patients but there are no reports of its use in pediatric patients. We present our experience with three kidney transplant recipients with BKVAN who received leflunomide. Three male patients aged 9, 12, and 20 yr developed BKVAN at 9, 12, and 2 months after a kidney transplant. Immunosuppression was reduced and cidofovir was administered in all patients 2–3 wk apart. Due to inability to travel to receive cidofovir in one, lack of reduction in BK viral load in the second, and rising serum creatinine despite cidofovir in the third patient, we discontinued cidofovir and initiated leflunomide. Teriflunomide target trough levels were 30–60 μg/mL. The patients received leflunomide for 27, 26, and 24 months, respectively. BK viral load decreased below 1000 DNA copies/mL in one and was undetectable in two patients after beginning leflunomide. All patients tolerated leflunomide without side effects. Leflunomide use in a select group of patients is well tolerated and may provide an alternative for treatment of BKVAN in pediatric patients.     

CYTOMEGALOVIRUS (CMV) INFECTIONS IN CHILDREN UNDERGOING HEMATOPOETIC STEM CELL TRANSPLANTATION

Cytomegalovirus (CMV) is one of the major causes of morbidity and mortality after hematopoetic stem cell transplantations (HSCT). The purpose of the study was to analyze risk factors of CMV disease in children undergoing HSCT. A total of 110 children who undergone hematopoetic stem cells transplantation were analyzed. In 16 patients (14.5%) CMV antigenemia in white blood cells was diagnosed. Most patients with CMV infection had undergone alloHSCT; one patient had undergone autologous transplantation. Second CMV reactivation in 4 of 16 patients was observed. Acute GvHD occurred in 11/15 patients. Early onset of CMV infection in 13/16 patients and late onset in 3/16 patients were diagnosed. CMV serological status of the donor and recipient before transplantation in children with CMV antigenemia was analyzed. The risk factors of CMV infection in analyzed group of children were type of transplant, recipient seropositivity before transplantation, and presence and intensity of GvHD. In most cases reactivation of CMV infection was diagnosed. CMV infection can also occur in the late post-transplantation period. CMV reactivation can occur in patients after autologous HSCT.     

Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia

Autoimmune cytopenias (AIC) following allogeneic hematopoietic stem cell transplantation (HSCT) may cause significant morbidity and mortality and are often challenging to treat. We present a case of a pediatric patient with primary myelofibrosis of infancy caused by VPS45 protein deficiency, who developed severe refractory hemolytic anemia and immune‐mediated thrombocytopenia 3.5 months following HSCT. After the failure of several treatments, he received daratumumab, an anti‐CD38 specific antibody, and demonstrated fast and sustained response. The only side effect was delayed recovery of humoral immunity. Daratumumab, by targeting antibody‐producing plasma cells, may be a valid treatment option for refractory post‐HSCT AIC.     

BK virus encephalitis and end‐stage renal disease in a child with hematopoietic stem cell transplantation

BK virus encephalitis after HSCT is uncommon. Several reports of native kidney BKVN in patients with HSCT, hematologic malignancies, human immunodeficiency virus infection, and non‐renal solid organ transplantation have been described. However, an uncommon combination of BK encephalitis and ESRD of native kidneys secondary to BK virus in a child with HSCT has not been described. We report a 10‐year‐old boy who presented with a gradually rising serum creatinine during treatment for severe autoimmune hemolytic anemia, which he developed 9 months after receiving an allogeneic HSCT for aplastic anemia. There was no proteinuria or hematuria present. Serum BK virus load was 5 × 10⁶ copies/mL. A renal biopsy showed evidence of BKVN. He developed fever, seizures, and confusion, and the (CSF) showed significant presence of the BK virus (1 × 10⁶ copies/mL) along with biochemical evidence of viral encephalitis. Cerebrospinal fluid cultures were negative. Despite significant clinical symptoms and presence of BK virus in CSF, the magnetic resonance brain imaging findings were minimal. With reduction of immunosuppression, there was resolution of BK encephalitis but BKVN remained resistant to multiple anti‐BK virus agents, including leflunomide and cidofovir. He eventually became dialysis‐dependent and, 6 years later, received a renal transplant from his mother. This case illustrates that BK virus in severely immunocompromised HSCT recipient may lead to BK encephalitis and BKVN of native kidneys, even without hemorrhagic cystitis, leading to ESRD. Knowledge of such is important for appropriate timely evaluation and management.     

异基因造血干细胞移植治疗IV期儿童神经母细胞瘤

目的：儿童IV期神经母细胞瘤生存期短,且目前尚无有效治疗措施。 该文通过异基因造血干细胞移植治疗IV期儿童神经母细胞瘤来评价其安全性及疗效。方法：对1例7岁IV期神经母细胞瘤患儿进行异基因造血干细胞移植治疗,供者为患儿母亲,HLA配型半相合,采用氟达拉滨,马法兰为预处理方案,G-CSF动员的外周血和骨髓联合移植。结果植入成功,移植后＋10 d中性粒细胞>0.5×109/L,＋11 d血小板>20×109/L。移植后+8 d出现II度肠道急性移植物抗宿主反应,治疗后缓解。随访210 d健康生存。结论： 对IV期儿童神经母细胞瘤患者,以父母为供体的半相合移植是一种可选择的、安全的、有效的挽救性治疗措施之一。     

Successful treatment of primary refractory acute myeloid leukemia with megadose stem cell transplantation, bone marrow boost and reduced intensity conditioning avoiding chronic graft vs. host disease and severe late toxicity

We report on a 9-yr-old boy suffering from primary refractory AML. Remission was not achieved after two courses of induction therapy, leading to prolonged aplasia for more than 3 months and severe infection. Therefore, the boy was treated with a reduced intensity conditioning regimen consisting of fludarabine, cyclophosphamide and OKT3. Megadose transplantation of highly enriched CD34+ peripheral stem cells from his HLA-identical brother, followed on day +11 by a boost of unmanipulated bone marrow, was performed. Regeneration of donor hematopoiesis was rapid and led to resolution of infection. No additional donor lymphocyte infusions were necessary. More than 4 1/2 yr after the transplant the boy remains in complete continuous remission with no evidence for chronic GvHD or other late effects. Therefore, we conclude that reduced intensity conditioning in combination with allogeneic megadose stem cell transplantation and bone marrow boost may have helped to achieve cure from primary refractory AML as well as a good quality of life for this boy.