Allograft with unrelated donor accentuates the gastrointestinal toxicity associated with high-dose melphalan and total body irradiation preparative for bone marrow transplantation in children

The use of high-dose melphalan (L-phenyalalanine mustard or L-PAM) has been shown to be associated with both hematological and non-hematological toxicity. It has been employed in the conditioning for allogeneic stem cell transplants from related donors but experience on its use in the unrelated setting has not been reported. As an attempt to elucidate the role of high-dose L-PAM (210 mg/m2) and total body irradiation (TBI) as a preparative regimen for allogeneic marrow transplantation from matched unrelated donors, they were employed in an institutional pilot series of seven pediatric patients. When compared with recipients of unrelated marrow grafts conditioned using other regimens, those treated with high-dose L-PAM experienced a markedly more severe acute graft-vs.-host disease (GvHD). The overall incidence of grade III-IV acute GvHD was higher (86% vs. 14%) among those treated with L-PAM. As judged by gastrointestinal (GI) symptoms, clinically significant (stages +2 to +4) gut GvHD was strikingly more prevalent among those treated with L-PAM (86% vs. 9%, p < 0.005). Toxic mortality prior to day + 100 was 29% in the L-PAM group and 9% in the non-L-PAM group of patients. With a mean follow-up of 21 months no increase in the incidence of chronic GvHD has been encountered among those conditioned with L-PAM. We conclude that the use of preparative L-PAM for allogeneic transplants from unrelated donors is associated with considerable procedure-related toxicity. We strongly suggest its use in this setting to be viewed with caution.     

Chemotherapy versus bone marrow transplantation in childhood acute lymphoblastic leukaemia

Twenty-five years ago over 90% of children with acute lymphoblastic leukaemia (ALL) died of this disease. Dramatic improvement has been achieved since then by employing risk-adapted, aggressive polychemotherapy protocols. More than 90% of children with ALL treated according to, for example BFM-protocols, have nowadays cure rates in the range of 70%–80%. However, 10% of patients do not initially respond adequately to standard induction chemotherapy. They are characterized by distinct chromosomal abnormalities such as translocation (9; 22) or combinations of early treatment failure and other risk factors as cytogenetic abnormalities, lineage-specific surface markers or tumour load at diagnosis. In this group of patients in first complete remission and certainly in the vast majority of relapsed patients, allogeneic bone marrow transplantation (BMT) has evolved as an alternative approach allowing further intensification of myeloablation and the introduction of an additional antileukaemic alloreactivity. Nevertheless, the decision for a marrow transplant in children has to be made very carefully because of a significant increase in treatment related mortality and BMT-specific risks like acute and chronic graft-versus-host disease with a critical iatrogenic chronic morbidity. This is even more evident, if mismatched or unrelated transplants are being considered. The indications for one or the other treatment modality according to the current BFM strategy are discussed.     

非亲缘异基因骨髓移植治疗儿童白血病

目的　评价非亲缘异基因骨髓移植 (URD BMT)治疗儿童急性和慢性白血病的临床疗效。方法　 6例白血病患儿 ,其中慢性髓系白血病 2例 ,急性淋巴细胞白血病 3例 (第 1次完全缓解 ) ,急性早幼粒细胞白血病 1例 (第 2次完全缓解 ) ,由台湾慈济骨髓捐赠中心提供无关供者骨髓。预处理方案为马利兰 环磷酰胺 (Bu/Cy2 )方案 ,急性移植物抗宿主病 (aGVHD)预防为霉酚酸酯(MMF)、环孢菌素A(CsA)加氨甲喋呤 (MTX)联合方案 ;以前列素E1预防肝静脉闭塞病 (VOD) ,以巨细胞病毒 (CMV)抗原血症监测和更昔洛韦预防CMV病。供、受者间HLA基因位点型全相合 3例 ,1个基因位点型不合 2例 ,2个基因位点型不合 1例。结果　 6例患儿经DNA短串联重复序列多态性分析证明为供髓植入 ,中性粒细胞 >0 5× 10 9/L的中位天数为 14 5 (13～ 18)d ,血小板 >2 0×10 9/L的中位天数为 16 (11～ 2 3)d。发生Ⅱ～Ⅳ度aGVHD 2例 (33% ) ,局限性慢性移植物抗宿主病(cGVHD) 3例 ,未发生广泛性cGVHD。中位随访时间 4 12 (187～ 1338)d ,全部患儿均无病生存。结论非亲缘异基因骨髓移植是治疗儿童急性和慢性白血病的有效方法。     

CD25抗体预防移植物抗宿主病在儿童白血病半匹配骨髓移植中的应用

目的　探讨CD2 5抗体用于预防儿童白血病半匹配未去除T细胞骨髓移植重度移植物抗宿主病 (GVHD)的疗效。方法　 10例儿童白血病患者接受人类白细胞抗原 (HLA) 2～ 3个位点不合半匹配骨髓移植 ,移植方法除了供者用粒细胞集落刺激因子 (G CSF)及受者应用环孢素A(CSA)、氨甲蝶呤 (MTX)、抗胸腺细胞球蛋白 (ATG ,FreseniusHemocare ,Germany)和霉酚酸酯 (MMF)预防GVHD的综合措施外 ,加用抗CD2 5单克隆抗体 (舒莱 ,novartispharmaswitzerland)预防GVHD ,剂量各为 2 0mg ,在移植前 2h和移植后第 4天应用 ,观察移植后的疗效 ,移植结果与前期未用CD2 5抗体移植组作回顾性比较。结果　 10例移植后均获造血重建 ,粒细胞 >0 5× 10 9/L的中位天数是 19d ,血小板大于 2 0× 10 9/L的中位天数是 2 2d ,骨髓植活直接证据检测证实为完全供者造血。无一例发生急性Ⅱ～Ⅳ度GVHD ,未用CD2 5抗体对照组 8例中发生急性Ⅱ～Ⅳ度GVHD有 4例 ,差异有显著性(P =0 0 14 7)。可评价慢性GVHD的 8例均发生慢性GVHD ,为局限性慢性GVHD。中位随访 12个月 (范围 9～ 2 4个月 ) ,2例为移植相关死亡 ,1例移植后 14个月因复发死亡 ,实际无病生存率是70 %。结论　儿童半匹配未去除T细胞骨髓移植中应用舒莱 ,明显降低急性重症GVHD发生 ,临床     

Allogeneic and autologous bone marrow transplantation for acute non-lymphoblastic leukaemia

Bone marrow transplantation (BMT) has had an increasing role in the treatment of acute nonlymphoblastic leukaemia (ANLL). A review of patients transplanted between May 1975 and August 1991 was undertaken in order to evaluate problems and outcome, and examine the role of both autologous and allogeneic BMT at various stages in the treatment of ANLL. Forty-seven patients received either an allogeneic ( n = 24) if a suitable donor was identified or autologous ( n = 23) BMT if there was no allogeneic donor. Conditioning therapy consisted of total body irradiation (TBI) and cyclophosphamide ( n = 14) or busulfan and cyclophosphamide ( n = 33) with or without melphalan. Graft-versus-host disease prevention was with methotrexate ( n = 9), methotrexate and cyclosporin ( n = 10) or T cell depletion ( n = 5). Minimum follow-up for surviving patients was 24 months (median 65 months). For patients transplanted in first remission there was a 0% and 9±6% transplant-related mortality, a 37±11% and 33±12% relapse risk and a 63±11% and 63±12% event-free survival for autologous and allogeneic BMT, respectively. In second remission, there was a 14% mortality, 50±20% relapse risk and 43±19% event-free survival for allogeneic BMT. No patient transplanted in relapse survived. In patients who survived greater than 24 months, late side effects were noted in all 8 (100%) patients given TBI and in 2 of 19 (10.5%) given busulfan. These data indicate that both allogeneic and autologous BMT are associated with significant event-free survival when used both as initial therapy after complete remission has been achieved with conventional chemotherapy or in second remission. Allogeneic and autologous BMT would appear to be similarly effective.     

以静脉马法兰为主的预处理自身移植治疗43例儿童高危恶性实体肿瘤

目的评价以静脉马法兰为主的预处理方案自身移植治疗儿童高危恶性实体肿瘤的安全性、有效性,探索中国儿童合适的静脉马法兰剂量。方法用回顾性分析的方法,对43例以静脉马法兰为主的预处理移植治疗的儿童高危恶性肿瘤临床资料进行分析。骨髓移植者采用卡铂350mg/m2.d×2+足叶乙甙(VP16)300mg/m2.d×2+马法兰(总量140mg/m2),外周血干细胞移植者采用卡铂300mg/m2.d×4+VP16160mg/m2.d×4+马法兰总量210mg/m2(移植前化疗休疗≥30天血象尚不能恢复正常或自身干细胞采集有核细胞数量不足3×108/kg者选用180mg/m2马法兰),临床观察药物的毒副反应并评估造血重建速度及患者预后。结果本组平均年龄7.6±4.2(1~17)岁,平均体重26.8±13.9(9.5~52)kg。因2例患儿连续进行2次移植,43例患儿共进行45例次移植,8例为骨髓移植、37例次为外周血造血干细胞移植,8例次患儿应用140mg/m2马法兰,10例应用180mg/m2马法兰,其余27例次应用210mg/m2马法兰。马法兰使用后26例次(57%)患儿出现腹泻,大多伴有腹痛、心前区不适及口腔黏膜炎,除1例应用马法兰180mg/m2患儿出现移植后造血功能恢复不良外,其余患儿平均11.4±8.5天中性粒细胞>0.5×109/L,21.4±9.5天血小板恢复至20×109/L以上。3个不同马法兰剂量组间造血恢复能力无明显差异。本组平均随访16.1±14.2个月(2~65个月),17例(39%)患儿平均移植后14.2±9.6个月(3~34个月)复发,其中12例为神经母细胞瘤。本组无移植相关的死亡,迄今仍有26例(61%)患儿处于无病生存状态。结论180mg/m2~210mg/m2的马法兰结合卡铂(300mg/m2.d×4)+VP16(160mg/m2.d×4天)用于自身造血干细胞移植治疗儿童晚期恶性实体肿瘤是安全有效的;黏膜炎是静脉马法兰应用后最常见的副反应;对于干细胞数量充足、化疗后骨髓恢复能力尚佳的移植患者以210mg/m2的马法兰剂量为妥;晚期神经母细胞瘤的治疗有待于探索更有效的方案。     

非血缘相关骨髓移植治疗重型地中海贫血的临床研究

目的为进一步拓展供髓源,探讨非血缘相关骨髓移植治疗重型地中海贫血(简称地贫)的可行性。方法9例地贫患儿进行了非血缘骨髓移植,其基因突变类型为地贫纯合子或双重杂合子,均确诊为重型β地贫。HLA高分辨配型全相合2例,1个亚型不合5例,2个亚型不合2例,6例红细胞血型不合。预处理为白消安16mg/kg,分4天口服;环磷酰胺200mg/kg,分4天静滴;抗人胸腺细胞免疫球蛋白30mg/kg,分3天静滴和氟达拉宾125mg/m2,分3天静滴。环孢素A和氨甲蝶呤预防移植物抗宿主病(graftversushostdisease,GVHD)。结果9例患儿均出现明显的过敏反应,1例有一过性低血压,皮肤急性GVHD7例,肝脏GVHD1例,肠道GVHD2例,慢性GVHD1例,高血压脑病1例,间质性肺炎2例。1例急性肺出血死亡。外周血中性粒细胞>0.5×109/L的时间为12～26天,WBC恢复正常的时间为23～110天,PLT于61～142天>50×109/L,Hb则于23～116天升至100g/L,最后一次输血时间为13～62天。PCR扩增短串联重复序列检测证实:8例患儿获得完全供体植入,1例未植入。随访6～24个月,7例原重型β地贫基因已消失,5例血型不合者已转成供者相同血型;7例患儿术后无需输血,Hb维持在110g/L以上。结论本组9例重型地贫的非血缘骨髓移植为国内首次尝试,初步证明非血缘骨髓移植根治重型地贫较安全可靠,为解决本病移植治疗的供髓源提供了新途径。     

Treatment of high-risk solid tumors of childhood with intensive therapy and autologous bone marrow transplantation

Autologous bone marrow transplantation (ABMT) allows delivery of intensive, marrow-ablative chemotherapy or chemoradiotherapy to children with high-risk solid tumors. Results from several studies of neuroblastoma suggest that outcome is improved by ABMT; however, relapses can occur months to years after complete clinical remission. Other high-risk tumors including peripheral neuroepithelioma, Ewing's sarcoma, rhabdomyosarcoma, Wilms' tumor, and brain tumors also appear to be responsive to intensive marrow-ablative therapy, although few studies have been reported. For tumors that can metastasize to marrow, a sensitive method is necessary for detecting tumor cell contamination. Immunocytologic analysis with monoclonal antibodies can identify one neuroblastoma cell per 10(5) normal marrow cells; this method also is applicable to other tumors with appropriate antibodies. Ex vivo removal (purging) of tumor cells decreases the probability of infusing tumorigenic cells with the ABMT. There is considerable experience in tumor detection and purging for neuroblastoma, but little has been done for other childhood solid tumors. Future investigations of ABMT will aim to further increase disease-free survival by intensifying induction and marrow-ablative regimens and by developing therapies to be given after ABMT that are directed at minimal residual disease. As pilot investigations mature, the efficacy of ABMT and conventional chemotherapy will be compared in multi-institution randomized studies.     

Cataracts after autologous bone marrow transplantation in children

We recorded the incidence and degree of posterior subcapsular cataract (PSC) in 29 children who had undergone autologous (n = 28) or syngeneic (n = 1) bone marrow transplantation (BMT) due to haematologic or lymphoid malignancy. Conditioning prior to transplantation consisted either of a combination of chemotherapy and total body irradiation (TBI) (n = 21) or of chemotherapy only (n = 8). TBI was given in one fraction of 7.5 Gy. Nine patients had received previous cranial irradiation. The patients were followed for 4-10y (median 8 y) after transplantation. Of 29 patients, 22 developed PSC, all within 4 y after BMT. With the exception of one patient who developed unilateral PSC, all had received TBI. Conversely, 100% of those who received TBI developed PSC. In this group (+TBI), eight patients (38%) developed significant PSC, defined as best corrected visual acuity <0.8 in either eye. Six patients (10 eyes) have since needed surgical repair consisting of extracapsular cataract extraction and intraocular lens implantation. There was no clear relationship between previous cranial irradiation and cataract development, nor any other obvious baseline differences between those in the +TBI group who developed significant PSC and those who did not. Although effects of previous therapy cannot be ruled out, TBI appears to be the main cause of PSC in this group of patients. Twelve patients in the +TBI group had well-preserved visual acuity throughout the study, reflecting a slow progression of PSC. This compares favourably with previous reports of allogeneic BMT, possibly owing to less need for corticosteroids after autologous BMT. We conclude that the incidence of PSC was high after autologous BMT where the conditioning regimen included total body irradiation.     

Granulocyte-colony-stimulating factor after allogeneic and autologous bone marrow transplantation in children

We evaluated the use of granulocyte CSF (G-CSF) after both allogeneic BMT (allo-BMT) and autologous BMT (ABMT) in children. After allo-BMT, G-CSF was used in 15 children who were compared with 20 historical controls. The ABMT patients were two sequential groups: the G-CSF group of 13 children and 11 historical controls. The patients were conditioned with different high-dose chemotherapy regimens with or without total body irradiation. G-CSF was administered at 5 μg/kg/day s.c. and was continued until an absolute neutrophil count (ANC) of 1,000 × 10⁶/l was reached. Following allo-BMT, G-CSF accelerated myeloid engraftment with a difference of 5 days at the ANC level of 500 × 10⁶/l (P < 0.02) and 9 days at 1,000 × 10⁶/l (P < 0.001). In the ABMT patients, G-CSF also accelerated myeloid engraftment. The difference between the G-CSF group and the control group was 6 days at ANC 200 (P < 0.05), 11 days at ANC 500 (P < 0.02), and 17 days at ANC 1,000 (P < 0.005). In the ABMT patients, benefit by G-CSF was also observed in a smaller number of days with fever and days on antibiotics. We conclude that G-CSG significantly accelerated myeloid engraftment, after both allogeneic and autologous BMT in children, and also decreased the duration of febrile illness in the ABMT patients. © 1996 Wiley-Liss, Inc.     

Experience with high dose multiagent chemotherapy and autologous bone marrow rescue in the treatment of twenty-two children with advanced tumours

Intensive chemotherapy followed by infusion of cryopreserved autologous bone marrow (ABMR) was used in the treatment of 22 children with advanced tumours. In nine this was their initial therapy; in eight it was used after partial or complete remission had been achieved with standard therapy; and in five, after relapse had occurred. Recovery of marrow function occurred in 20 patients with a mean time of 13.2 and 18.2 days to recovery of neutrophils (>0.5 × 10⁹/t) in newly diagnosed and previously treated patients respectively. Platelet count recovery to >50 × 10⁹/l occurred in a mean time of 13.4 days in newly diagnosed and 20.4 days in previously treated patients. Control of extensive local tumour was obtained in three of three evaluable patients with abdominal non-Hodgkin's lymphoma (NHL). Metastatic bony and marrow disease was controlled in two of two patients with retinoblastoma. In Ewing's sarcoma, temporary control of widespread metastatic disease occurred in one patient. In the other, eradication of extensive local mass disease at the primary site had been achieved. Poor response to-treatment has been seen in seven of eight patients with Stage III or IV rhabdomyosarcoma, three patients with neuroblastoma and four of five patients with recurrent disease Apart from the anticipated bone marrow toxicity, the major complications were severe mucositis, anaphylaxis following bone marrow infusion and haemorrhagic cystitis. The presence of herpes simplex infection appeared to aggravate mucosal complication. We suggest that intensive chemotherapy and ABMR has a place in the treatment of tumours in which there is evidence of sensitivity to high doses of cyclophosphamide, or where synergy of drugs such as cyclophosphamide and adnamycin may be expected to increase tumour cell kill. The ability to control extensive intra-abdominal disease in NHL may eliminate the need for total abdominal irradiation in that disease.     

Autologous bone marrow transplantation for pediatric Wilms' tumor: The experience of the European bone marrow transplantation solid tumor registry

This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary. © 1994 Wiley-Liss, Inc.     

Addison disease 10 years after bone marrow transplantation for Wiskott-Aldrich syndrome

We report a 10-year-old boy with familial Wiskott-Aldrich syndrome (WAS) who underwent successful bone marrow transplantation (BMT) at the age of 9 months. With the exception of auto-immune haemolytic anaemia due to warm antibodies lasting 15 months there had not been any complication after BMT. Ten years later the patient presented with diarrhoea, hyperpigmentation of skin and oral mucosa, fatigue and polyuria. Diagnosis of Addison disease was confirmed by typical electrolyte imbalance and absent cortisol response to adrenocorticotrophic hormone. Adrenal antibodies were positive. On therapy with oral gluco- and mineralocorticoids, the symptoms disappeared and electrolytes normalized. To our knowledge auto-immuno endocrinopathy after BMT for WAS has not yet been reported.     

HLA部分相合父母供髓骨髓移植二次治疗重型地中海贫血

目的探讨同胞脐血植入失败的重型β地中海贫血患者,应用HLA部分相合父母亲骨髓进行第二次移植的效果。方法两例分别应用同胞HLA2个位点不合和全相合脐血移植的重型β地中海贫血患者,首次移植后均发生植入失败,前者表现为重型再生障碍性贫血,后者自体造血恢复。分别于首次移植13、12个月后,应用HLA部分相合的父亲、母亲骨髓进行第二次移植,观察临床疗效。结果一例重型再生障碍性贫血患者,应用HLA4个位点相合的父亲骨髓进行第二次移植,再次发生植入失败;另一例自体恢复者,应用HLA5个位点相合的母亲骨髓进行第二次移植获成功植入,现已脱离输血20个月。结论在选择合适的移植时机和预处理方案的前提下,父母供髓的二次移植对植入失败的重型β地中海贫血可起到有效的治疗作用。     

Normal long-term parathyroid function after autologous bone marrow transplantation in children

Parathyroid function was recently reported to be affected in more than one-third of pediatric BMT patients conditioned without irradiation. Our aim was to describe parathyroid function in children with malignant hematological disease after autologous BMT with and without TBI. PTH, albumin-corrected serum calcium, and serum phosphate were analyzed in 35 children followed for six months to nine yr after BMT. Twelve patients were conditioned with chemotherapy alone, and 23 patients received TBI as well. In the TBI group, 11 patients had previously received additional CRT. We found normal levels of PTH in children post-BMT, with the exception of four patients (11%) who showed transient PTH elevation during the first year of follow-up, There was no difference between those who had received irradiation and those who had not. Serum calcium was unchanged after BMT. An age-corrected quotient of serum phosphate decreased slightly. Renal function which was normal before BMT decreased slightly in both groups after BMT, but was within the normal range. Parathyroid function was found to be normal during the time frame of this study, irrespective of whether irradiation had been given.     

Hypertrophic cardiomyopathy in mucopolysaccharidoses: Regression after bone marrow transplantation

Summary Mucopolysaccharide storage disease (MPS) presents clinically with a broad spectrum of abnormalities, among which cardiovascular involvement has been described.The echocardiographic findings have recently been reported for the various types of MPS. Among these, asymmetric septal hypertrophy (ASH) has been documented.We present a case of a 9-year-old girl suffering from type I MPS, atypical variant, with echocardiographic signs of ASH. She was given a bone marrow transplant after which the hypertrophic cardiomyopathy regressed.     

Pubertal development and growth after total-body irradiation and bone marrow transplantation for haematological malignancies

Pubertal development after total-body irradiation (TBI) was investigated in 40 children (21 boys) treated with allogeneic bone marrow transplantation (BMT) for haematological malignancies at a mean age of 11.3 years. The mean age at the last visit was 19.0 years. Twenty-five patients (15 boys) were prepubertal at BMT. Data on secondary sexual characteristics, the pituitary-gonadal axis and longitudinal growth were retrospectively collected from the medical records. In boys not receiving additional testicular irradiation (n = 19), penile growth and pubic hair development was normal and all had serum testosterone levels within the adult range. The majority of them, however, had incidental elevations of LH, suggesting minor Leydig cell damage. Testicular volume at last measurement was small (mean: 10.5 ml) and serum FSH levels were elevated in all boys, with normalisation in only one, suggesting severe impairment of reproductive gonadal function. Of the ten girls who received BMT before puberty, six had a spontaneous onset of puberty and menarche; the four other girls needed hormonal substitution therapy. Recovery of gonadal function after cessation of substitution was seen in one girl, who became pregnant but had a spontaneous abortion. Decrease in height SDS was seen in the majority of patients and was positively correlated with male gender and lower age at the time of BMT. Conclusion Careful monitoring of both gonadal function and growth after bone marrow transplantation and total body irradiation is warranted in order to detect disturbances early and ensure normal pubertal development in children treated for haematological malignancies. Received: 30 December 1998 / Accepted: 15 May 1999     

Evans syndrome after unrelated bone marrow transplantation for refractory cytopenia of childhood

Post‐transplant ES, which is often resistant to therapies, has seldom been described. This report describes a case of ES after UBMT for RCC. A five‐yr‐old boy developed RCC with no evidence of monosomy 7. Because no matching family donors were available for SCT and immunosuppressive therapy was ineffective, UBMT was performed when he was six yr old. The conditioning regimen included TAI (3 Gy) and administration of FLU, CY, and rabbit antithymocyte globulin. The recovery of blood cells was good. He displayed grade II acute GVHD involving only the skin. ES developed on day 66, with positive results for Epstein–Barr virus DNA and HHV 6. Cytopenia was resolved with treatment with RTX, GCV, an escalated dose of steroids, high‐dose gammaglobulin, and romiplostim. No relapse has occurred since discontinuing steroids on day 177 and romiplostim on day 268. Post‐SCT ES after UBMT is rare, and the risk factors and therapies are unclear. Prospective analysis and collection of cases from multiple centers are required for clarification.     

Normal spontaneous cortisol secretion in children after autologous bone marrow transplantation

AIM: To describe spontaneous cortisol secretion in children after autologous bone marrow transplantation (BMT) for acute leukaemia and lymphoma. METHODS: Spontaneous cortisol secretion was analysed in 39 children before and after BMT. Thirteen patients were conditioned with chemotherapy only (group 1), and 26 patients also with total body irradiation (TBI). In the TBI group, 14 patients had received no additional irradiation (group 2), whereas 12 patients had received cranial irradiation (CRT) previously (group 3). RESULTS: Before BMT, in comparison with group 1, mean morning cortisol was significantly lower in group 2 (252 vs 415 mmol/l, p = 0.004), but not in group 3 (vs 312 mmol/l, p = 0.12). There was no change in group 1 six months after BMT (to 379 nmol/l), whereas morning cortisol increased significantly in group 2 and group 3 (to 386 and 343 nmol/l, respectively; p < 0.05). The change in mean morning cortisol correlated negatively with pretransplant morning cortisol (r = -0.63, p < 0.001). Neither TBI nor CRT were associated with changes in morning cortisol. CONCLUSION: Spontaneous cortisol secretion is maintained after BMT irrespective of whether cranial or total body irradiation has been given or not.     

Renal function after conditioning therapy for bone marrow transplantation in childhood

The knowledge of renal function in the course of BMT is poor. We prospectively investigated glomerular and tubular function in 42 children who underwent BMT because of malignancy. Seventeen children were transplanted autologously. Investigations were performed before and immediately after the conditioning regimen. Inulin- and creatinine clearance, albuminuria, urine excretion of α₁-microglobulin, β-N-acetylglucosaminidase, alanine-aminopeptidase, intestinal alkaline phosphatase, and Tamm-Horsfall-Protein as well as sodium-and phosphatreabsorption were measured. The patients were classified regarding use of total body irradiation (fTBI) in the conditioning regimen. Before CR: Glomerular filtration rate (GFR) was not influenced by the underlying diagnosis of previous treatment. Mean GFR was elevated compared with the reference group. Microalbuminuria was elevated in 15% of patients, and mean levels were higher than in the reference group. Proximal tubular dysfunction was indicated by an elevated excretion of α₁-MG in 54% of β-NAG in 66%, of AAP in 40%, and of IAP in 47%. Fractional sodium excretion was abnormal in 21%, phosphate reabsorption in 5% and THP-excretion in 7% of the patients. After CR: Creatinine clearance was not affected by CR. After CR α₁-MG, β-NAG, FE_Na, AAP, and IAP were increased compared with values before CR. TP/Cl_α was decreased. Excretion of THP was not altered by CR. In patients without fTBI there was a greater increase in α₁-MG excretion and decrease in phosphate reabsorption after CR compared with patients conditioned with fTBI. We conclude that significant proximal tubular dysfunction is present in about 50–60% of patients before and in nearly all after CR. Distal tubular function was less severely affected. Severity of nephrotoxicity after CR did not correlate with pre-existing abnormalities. Med. Pediatr. Oncol. 28:274–283. © 1997 Wiley-Liss, Inc.