High-dose busulfan and melphalan as conditioning regimen for autologous peripheral blood progenitor cell transplantation in high-risk neuroblastoma patients

The aim of this retrospective study was to analyze the outcome and identify risk factors associated with progression-free survival (PFS) in 36 children with high-risk neuroblastoma who underwent autologous peripheral blood progenitor cell (PBPC) transplantation between 1994 and 2010. The conditioning regimen used in all cases consisted of high-dose of busulfan and melphalan. Median age at transplantation was 3 years (range: 0.7-14 years). The median times to neutrophil and platelet engraftment were 11 days (range: 9.16 days) and 13 days (range: 9.33), respectively. Twenty-one patients developed nonhematologic toxicity: 15 patients had mucositis, 4 patients developed an engraftment syndrome, and there were 2 cases of liver toxicity. No toxic deaths were observed. There were 15 patients who relapsed. The median time to relapse was 6 months after the transplant (range: 3-13 months). With a median follow-up of 55 months (range: 4-180 months), the PFS was 57% ± 8.5% for the whole group. In multivariate analysis, age below 3 years (P < .005), complete remission (CR) pretransplantation (P < .07) and 1p germline status (P < .01) were variables associated with better outcomes. Patients who were or achieved early CR following transplantation (3 months posttransplantation) had a probability of PFS of 91% ± 6% as compared to patients who did not (PFS 9% ± 8%) (P < .0001). This retrospective study shows that high dose of busulfan and melphalan as conditioning regimen in children with high-risk neuroblastoma is associated with very low morbidity and no mortality in the authors' hands. Younger patients with no 1p deletions and in first CR at transplantation had the better outcome.     

Busulfan, melphalan, and thiotepa with or without total marrow irradiation with hematopoietic stem cell rescue for poor-risk Ewing-Sarcoma-Family tumors

BACKGROUND: Survival following metastatic or recurrent Ewing sarcoma family tumors (ESFT) remains <25%. Myeloablative therapy with hematopoietic stem cell transplantation (HSCT) may improve survival for poor-risk ESFT. We describe the toxicity and efficacy of a myeloablative chemotherapy regimen, followed by a second myeloablative radiotherapy regimen as consolidation treatment for poor-risk ESFT. PROCEDURE: Sixteen patients with poor-risk ESFT were treated with myeloablative therapy followed by HSCT. All patients received busulfan, melphalan, and thiotepa (BuMelTT) as chemotherapy conditioning. Nine patients received total marrow irradiation (TMI) as a second myeloablative therapy, also followed by HSCT. Seven patients were excluded from TMI because of inadequate peripheral blood stem cell harvest, extensive prior radiation therapy, early disease progression, orpatient refusal. The disease status prior to my eloablative therapy was first complete response (CR1) in three patients, CR2 in nine, second partial response (PR2) in one, CR3 in one, and progressive disease (PD) in two. RESULTS: One patient died of regimen-related toxicity, one from late pulmonary toxicity, and one following allogeneic transplantation for myelodysplasia. Eight developed recurrent disease (median time to progression 6.8 months). Six survive without relapse from 27 to 66 months following BuMelTT (median follow-up 42 months), all of whom received both BuMelTT and TMI patients (3-year event-free survival 36%). CONCLUSIONS: Dual myeloablative therapy with BuMelTT and TMI was a feasible and promising treatment approach for patients with poor-risk ESFT. Inability to collect sufficient PBSC and extensive previous radiation therapy limit the ability to deliver TMI as a second HSCT conditioning regimen.     

Retrospective analysis of high-dose chemotherapy followed by autologous stem cell transplantation for high-risk pediatric osteosarcoma

Abstract

The outcomes of osteosarcoma with poor prognostic factors, such as poor responders, metastatic disease at diagnosis, and relapsed or refractory disease, are poor. We reviewed the clinical records of the patients diagnosed with osteosarcoma at our institute between 2004 and 2018 who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in our institute. Ten patients of osteosarcoma with poor responder, refractory status, and metastatic disease at diagnosis received high-dose chemotherapy followed by ASCT. Four patients underwent high-dose chemotherapy followed by ASCT with the conditioning regimen consisted of thiotepa and melphalan (MEL). Five patients underwent high-dose chemotherapy followed by ASCT with the conditioning regimen consisted of intravenous busulfan (BU) and MEL. One patient underwent tandem high-dose chemotherapy followed by ASCT with BU and MEL followed by carboplatin and etoposide. None of the ten patients died of regimen related toxicities. None of the five patients with poor responders who underwent high-dose chemotherapy followed by ASCT as part of consolidation therapy died of disease after ASCT. High-dose chemotherapy followed by ASCT might be effective for poor responders in osteosarcoma.     

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。     

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.     

Outcomes of children,adolescents, and young adults following allogeneic stem cell transplantation for secondary acute myeloid leukemia and myelodysplastic syndromes—The MD Anderson Cancer Center experience

We conducted a retrospective analysis of outcomes for children and young adults with sAML/sMDS who underwent HSCT at our institution. Thirty‐two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/sMDS diagnosis to HSCT was 4.1 months (range: 1.2‐27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow‐up of 62.3 months (range: 0.4‐250.9 months), 14 patients had disease recurrence. Acute GVHD, grade III/IV, occurred in three patients. Causes of death were as follows: disease relapse (n=12), infection (n=2), pneumonia (n=1), pulmonary hemorrhage (n=1), acute GVHD (n=1), and graft failure (n=1). A PS of ≥90% at the time of HSCT had a significant impact on PFS (P=.02). Patients achieving pretransplant primary CR (n=8) and those with sMDS and RA (n=6) had prolonged PFS (P=.04). On multivariate analysis, shorter time to transplantation (≤6 months from diagnosis of sAML/sMDS) was associated with superior OS (P=.0018) and PFS (P=.0005).     

CEM为预处理方案的自体外周血造血干细胞移植治疗晚期神经母细胞瘤相关毒性及疗效观察

目的　观察以CEM (卡铂 +VP 16 +马法兰 )为预处理方案的自体外周血造血干细胞移植治疗晚期神经母细胞瘤患儿的毒性和疗效。方法　研究经大剂量放、化疗及手术治疗达完全缓解的IV期神经母细胞瘤患儿 6例 ,采用CEM预处理方案 (卡铂每日 4 2 5mg/m2 共 4d ,VP 16每日 338mg/m2 共 4d ,马法兰每日 70mg/m2 共 3d)的自体外周血造血干细胞移植 ,并依据Bearman标准对预处理毒性进行评价 ,对其造血重建、并发症及预后进行观察。结果　预处理后髓外毒性除 1例为I级肝损害外 ,主要表现在口腔粘膜 (I级 6例 )和胃肠道 (I级 5例 ,II级 1例 )损害。白细胞于移植后 3± 0 .5d达到 0 ,移植后 33± 3.1d稳定于 1× 10 9/L以上。除 1例患儿移植后 11个月颅内转移外 ,余 5例患儿均健康存活。随诊时间分别为 8、10、2 3、36及 4 8个月。结论　以CEM为预处理方案的自体外周血造血干细胞移植可以安全、有效的治疗IV期神经母细胞瘤。     

Allogeneic bone marrow transplantation in juvenile myelomonocytic leukemia without total body irradiation

Allogeneic bone marrow transplantation (BMT) without a total body irradiation (TBI) conditioning regimen was investigated in children with juvenile myelomonocytic leukemia (JMML). Eight consecutive patients with JMML (n = 6) or monosomy 7 (n = 2) underwent BMT at a median age of 20 months. Donor source included fully matched related (n = 3), mismatched related (n = 2), or fully matched unrelated (n = 3). The conditioning regimen included busulfan, cyclophosphamide, and etoposide (VP16) (melphalan was substituted for VP16 in one patient). The first patient in the series underwent TBI. Graft-versus-host disease prophylaxis was with cyclosporin and methotrexate and in vivo T-cell depletion (Campath 1 g) for mismatched and unrelated transplants. Seven and two patients, respectively, received chemotherapy and splenectomy before BMT. At a median follow-up of 48 months after BMT, five patients remained in remission. The overall survival rate was 63% at 5 years. All deaths occurred in patients with refractory disease at the time of BMT. Allogeneic BMT without TBI appears to be effective therapy for JMML and avoids some of the potential late sequelae of TBI in preschool children.     

A conditioning regimen of busulfan, fludarabine, and melphalan for allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia

A pilot study was undertaken using a myeloablative conditioning with fludarabine, busulfan, and melphalan to improve the outcome of HSCT in 10 children, aged six months to six yr, with JMML. All patients were conditioned with oral busulfan (560 mg/m(2)), fludarabine (120 mg/m(2)), and melphalan (180-210 mg/m(2)) prior to HSCT, and received stem cells from bone marrow in seven cases, and from cord blood in three cases. Engraftment was documented in eight patients, whereas graft failure occurred in two, one of whom had received HLA-mismatched cord blood and other had received bone marrow from HLA-mismatched mother. Three patients, including two in who graft failure had occurred, relapsed. Five patients developed acute GVHD and two developed chronic GVHD. Seven patients are alive and in remission 27-69 months after transplantation. Thus, our study showed that HSCT following conditioning with fludarabine, busulfan, and melphalan was well tolerated and appeared to be effective for JMML.     

Hematopoietic stem cell transplantation (HSCT) with a conditioning regimen of busulfan, cyclophosphamide, and etoposide for children with acute myelogenous leukemia (AML): a phase I study of the Pediatric Blood and Marrow Transplant Consortium

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an important treatment modality for children with AML. The optimal conditioning regimen is unknown. The aim of this study was to determine the appropriate dosing of etoposide in combination with busulfan and cyclophosphamide in this setting. PROCEDURE: Twenty patients with a diagnosis of AML in first or second remission, or myelodysplasia scheduled for bone marrow transplantation, were included in this study. Patients received busulfan 640 mg/m(2) in 16 doses, cyclophosphamide 120 to 150 mg/kg in two doses, and etoposide from 40-60 mg/kg as a single dose. Extensive toxicity data was collected. RESULTS: Nineteen patients were evaluable for toxicity. Mucositis was seen in all patients. Four patients developed bacteremia and one patient died from overwhelming sepsis on day +3. Four patients developed moderate to severe skin toxicity. The major dose-limiting +3 toxicity was hepatic toxicity, which occurred in 14 of 19 patients. Eight patients developed clinical veno-occlusive disease, including three patients at dose level 4, two of whom had life-threatening disease. This hepatic toxicity defined the MTD of 640 mg/m(2) busulfan, 120 mg/kg of cyclophosphamide, and 60 mg/kg of etoposide. Overall, 9 of 20 patients enrolled in the study survive in remission, 8/14 allogeneic (median follow-up 44 months), and one of six autologous patients (follow-up, 54 months). CONCLUSIONS: We conclude that the combination of busulfan, cyclophosphamide, and etoposide at the doses defined above has activity in the treatment of children with high-risk AML/MDS undergoing allogeneic HSCT. Whether it offers an advantage over other conditioning regimens will require a randomized trial with a larger cohort of patients.     

The outcome of allogeneic hematopoietic stem cell transplants without total body irradiation in pediatric patients with acute lymphoblastic leukemia: single centre experience

The most widely accepted conditioning regimen to allogeneic hematopoietic stem cell transplantation consists of total body irradiation, especially in patients affected by acute lymphoblastic leukemia (ALL). In this retrospective study, we report our experience on hematopoietic stem cell transplantation in 44 pediatric patients with acute lymphoblastic leukemia using a non-radiation-based conditioning regimen (busulfan/cyclophosphamide). Median age at transplantation was 12.5 years (range, 4 to 14 y). 39 out of 44 patients received transplants in complete remission. At a median follow-up of 390 days, the probabilities of 3-year disease-free survival and overall survival were 50% and 68%, respectively. Disease status of hematopoietic stem cell transplantation was the only significant variable affecting the overall survival. Acute and chronic graft-versus-host disease occurred in 23 (64%) and 12(18%) patients, respectively. Relapse was significantly higher among patients transplanted in advanced disease status. The results of the study indicate that non-radiation-based preparative regimens can be used in pediatric patients with ALL. However, well-designed comparative trials are needed to better clarify the difference between radiation and non-radiation-based conditioning regimens in pediatric ALL.     

自体外周血造血干细胞移植在小儿恶性晚期实体肿瘤的临床应用(英文)

目的　小儿晚期实体肿瘤对常规化疗效果欠佳 ,该文探讨大剂量化疗并自体外周血干细胞移植(APBSCT)治疗小儿高危晚期实体瘤的可行性及疗效。方法　 1 3例恶性实体肿瘤患儿 (恶性淋巴瘤 7例、神经母细胞瘤 6例 ) ,在其完全缓解 (1 2例 ) ,部分缓解 (1例 )后进行了APBSCT治疗。移植时病程中位时间 1 0月。 1 1例用化疗加重组人粒 单细胞集落刺激因子 (rhGM CSF)或重组人粒细胞集落刺激因子 (rhG CSF)动员 ,2例采用常规化疗方案作为动员剂。所采集单个核细胞 (MNC)为 (6 .85± 2 .6 5 )× 1 0 8/kg。CD34+ 细胞为 (1 5 .82± 1 2 .93)×1 0 6/kg。CFU GM集落为 (1 7.87± 1 7.94 )个 / 1 0 4细胞。预处理方案中 6例基本方案为全身放疗加环磷酰胺。 7例未用TBI ,仅以马法兰为主做为预处理方案 (马法兰 +卡铂 +足叶乙甙 5例 ,白消胺 +马法兰 2例 )。结果　移植后白细胞 >0 .5× 1 0 9/L、>1 .0× 1 0 9/L、血小板 >2 0× 1 0 9/L的中位时间分别为 1 2天、1 5天、1 9天。中位随访时间4 8月 (1月～ 1 4 4月 )。至今总生存率 77% (1 0 / 1 3) ,死亡率 2 3% (3/ 1 3) ,无移植相关死亡。结论　APBSCT是治疗小儿晚期实体肿瘤 ,明显改善其预后的重要治疗方法。     

Double allogeneic peripheral blood stem cell transplantation in a 9-year-old patient with relapsed acute lymphoblastic leukemia: case report

A 9-year-old female patient with relapsed leukemia that was refractory to conventional reinduction chemotherapy was successfully treated with double allogeneic peripheral blood stem cell transplantation. The conditioning regimen for the first transplantation consisted of busulfan, etoposide, and melphalan, and that for the second transplantation was total body irradiation and thiotepa. Neither severe regimen-related toxicity nor graft-versus-host disease was observed. The patient is in complete remission without major complications for 5 years. Double transplantation should be considered as one of the possible treatments for refractory acute lymphoblastic leukemia.     

High‐dose treatment for malignant rhabdoid tumor of the kidney: No evidence for improved survival—The Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) experience

1 Background

Malignant rhabdoid tumor of the kidney (MRTK) is the most aggressive childhood renal tumor with overall survival (OS) rates ranging from 22% to 42%. Whether high‐dose chemotherapy with autologous stem‐cell transplantation (HDSCT) in an intensive first‐line treatment offers additional benefit is an ongoing discussion.

2 Methods

A retrospective analysis of all 58 patients with MRTK from Austria, Switzerland, and Germany treated in the framework of consecutive, prospective renal/rhabdoid tumor studies SIOP9/GPO, SIOP93‐01/GPOH (where SIOP is International Society of Pediatric Oncology and GPOH is German Society of Pediatric Oncology and Hematology), SIOP2001/GPOH, and European Rhabdoid Tumor Registry from 1991 to 2014.

3 Results

Median age at diagnosis was 11 months. Fifty percent of patients had metastases or multifocal disease at diagnosis (Stage IV). Local stage distribution was as follows: not done/I/II/III—1/6/11/40. Fifteen (26%) patients underwent upfront surgery. Thirty‐seven (64%) patients achieved a complete remission, 17 (29%) relapsed, 34 (59%) died of disease progression, and two (3%) died of treatment‐related complication. Mean time to the first event was 3.5 months. Two‐year EFS/OS (where EFS is event‐free survival) for the whole group was 37 ± 6%/38 ± 6%. Metastases/multifocal disease, younger age, and local stage III were associated with significantly inferior survival. Eleven (19%) patients underwent HDSCT (carboplatin + thiotepa, n = 6; carboplatin + etoposide + melphalan, n = 4; others, n = 1); 2‐year OS in this group was 60 ± 15% compared to 34 ± 8% in the non‐HDSCT group (P = 0.064). However, the time needed from radiologic to histologic diagnosis, stem‐cell harvest, and HDSCT must also be taken into account to avoid selection bias by excluding the highest risk group with early progression (<90 days). Thus, 2‐year EFS only for patients without progression until day 90 was 60 ± 16% consolidated by HDSCT compared to 62 ± 11% without (P = 0.8).

4 Conclusion

Our retrospective analysis suggests comparable outcomes for patients with and without HDSCT, if adjusted for early disease progression.     

ALLOGENEIC CORD BLOOD TRANSPLANTATION IN CHILDREN WITH HEMATOLOGICAL MALIGNANCIES: A Long-Term Follow-Up Single-Center Study

Forty-two consecutive pediatric patients with high-risk leukemia who received cord blood (CB) transplantation at the authors’ institution from January 1996 and December 2007 were included in this study. Age ranged from 6 months to 18 years and body weight from 7 to 73 kg. Twenty-nine patients had ALL and 13 AML. Twenty-seven out of 42 patients were transplanted in advanced phase of disease (beyond 2nd CR). For 13 patients the CB transplantation was their second transplant. The median follow-up for survivors was 60 months (range, 6–120 months). The probability of myeloid engraftment was 95 ± 5% and the median time to neutrophil >500/μL was 20 days (range, 12–54). The median time to platelet engraftment was 60 days (range, 37–200). The probability of relapse was 33 ± 9%. The nonrelapse mortality at day +100 after transplantation was 30 ± 7%. The probability of disease-free survival was 34 ± 7%. The CD34⁺ cell dose had a significant impact on DFS (HR, 3.28; 95% CI: 1.49–7.23; p =. 003). The results from a long-term follow-up study suggest that cord blood transplantation should be performed in the early phase of disease whenever possible. The cord blood unit for transplantation in pediatric patients with hematological malignancies should be chosen based on cell dose, especially a CD34⁺ cell dose.     

Acute toxicity and outcome among pediatric allogeneic hematopoietic transplant patients conditioned with treosulfan-based regimens

Abstract

Treosulfan-based regimens constitute a feasible and increasingly used, but still myeloablative, conditioning in pediatric allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the acute toxicity and outcome of all consecutive (2004–2015) pediatric HSCT patients prepared for HSCT with treosulfan in a single-center setting. We included HSCTs performed for both nonmalignant (n?=?23) and malignant diseases (n?=?11). The controls were patients with nonmalignant diseases or hematological malignancies conditioned with cyclophosphamide (Cy)-total body irradiation (TBI)-based (39 patients) or busulfan-based regimens (11 patients). The major toxicities of the treosulfan-based regimens were limited to oral mucosa and skin. 50% of the patients needed IV morphine for severe mucositis compared to 31% in patients conditioned with Cy-TBI (P?=?0.02). Other toxicities were rare. The disease-free survival (DFS) of patients transplanted for nonmalignant disorders was 88.9?±?7.5% at 2?years. The event-free survival (EFS) at 2?years in this small cohort for those with a malignant disease and a treosulfan-based conditioning was 54.5?±?1.5%. We conclude that a treosulfan-based conditioning regimen gives excellent DFS in pediatric HSCT performed for a nonmalignant disorder but with substantial mucosal toxicity. In a malignant disorder a treosulfan-based regimen looks promising but larger, preferably randomized, studies are needed to prove efficacy.     

Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors

Watanabe N, Takahashi Y, Matsumoto K, Horikoshi Y, Hama A, Muramatsu H, Yoshida N, Yagasaki H, Kudo K, Horibe K, Kato K, Kojima S. Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors.
Pediatr Transplantation 2011: 15: 642–649. © 2011 John Wiley & Sons A/S. Abstract: Although some studies have reported that TBI and MEL offer an effective conditioning regimen for autologous SCT in acute leukemia, little has been reported regarding outcomes of allogeneic SCT. We retrospectively evaluated outcomes for 50 pediatric patients who underwent allo‐SCT conditioned with intravenous MEL (180–210 mg/m²) and fractionated TBI (12–13.2 Gy) from HLA‐identical related donors. Nineteen patients were in CR1, 18 were in CR2, and 13 showed advanced‐stage disease (≥CR3). Patients had received allo‐SCT from HLA‐identical siblings (n = 45) or phenotypically HLA‐identical family donors (n = 5). Median duration of follow‐up for all disease‐free patients was 61 months (range, 8.8–177 months). At the time of analysis, 12 patients had died. Eleven of those died of relapse, and one died of TRM. DFS rates for all patients, patients with AML (n = 12), and patients with lymphoid malignancy (n = 38) were 61.4% and 82.1%, respectively. DFS rates for CR1, CR2, and ≥CR3 cases were 89.2%, 88.1%, and 23.1%, respectively (p < 0.05). MEL/TBI for pediatric patients with hematological malignancies was associated with lower relapse rates and no increase in toxicity, resulting in better survival.     

High-dose busulfan and cyclophosphamide as a conditioning regimen for autologous peripheral blood stem cell transplantation in childhood non-Hodgkin lymphoma patients: a long-term follow-up study

We analyzed the outcome in 22 children with refractory or relapsed non-Hodgkin lymphoma who underwent autologous peripheral blood progenitor cell transplantation between 1994 and 2009. The conditioning regimen used in all patients consisted of busulfan and cyclophosphamide. Median age was 6 years (range 2 to 16 y). The most common histologic subtype was Burkitt lymphoma. Ten patients were in complete remission and 12 in partial remission at the time of transplant. The median dose of CD34+ cells that was infused was 4.6 × 10/kg (range 2.1 to 58.7 × 10/kg). All the patients were engrafted, with a median time for neutrophils and platelets recovery of 11 (range, 8 to 15 d) and 14 (range, 9 to 60 d) days, respectively. Nonhematologic treatment-related toxicity included severe mucositis in 3 patients and hepatic sinusoidal obstruction syndrome in 1 patient. There were no transplant-related mortalities. With a median follow-up of 60 months (range, 4 to 180 d) the disease-free survival was 90 ± 6.5% for the whole group. This retrospective study shows a high long-term survival using busulfan/cyclophosphamide as conditioning regimen in children with refractory or relapsed non-Hodgkin lymphoma.     

Unrelated and related donor transplantation for beta‐thalassemia major: A single‐center experience from India

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with β‐thalassemia major. A matched sibling or a related donor is usually found in only 25%‐30% of the patients. There are limited data on matched unrelated donor (MUD) transplants from India. We reviewed HSCT outcome in 56 children with TM who underwent 57 transplants at our center. Related donor (RD) (n=43) and MUD (n=14) transplants were performed with TreoFluT‐based conditioning regimen in majority (95%) of patients. Peripheral blood stem cells (PBSC) were the preferred (85%) source of stem cells. The overall survival (OS) at 1 year in RD and MUD groups was 87.6±5.2% and 85.7±9.4% at a median follow‐up of 25 (1‐92) months and 22.5 (1‐50) months, respectively (P=.757). The thalassemia‐free survival (TFS) at 1 year was 87.6±5.2% and 77.1±11.7% with a median follow‐up of 24 (1‐92) and 16.5 (1‐50) months, respectively (P=.487). Although acute (14% vs 64%) and chronic graft‐versus‐host disease (GVHD) (13.9% vs 42.9%), infectious (39.5% vs 71.4%), and non‐infectious (37.2% vs 78.5%) complications are higher in MUD transplant group, the present data show a comparable OS and TFS among RD and MUD group with treosulfan‐based regimen using PBSC grafts.     

Successful matched-unrelated bone marrow transplantation in a patient with beta-thalassemia major

The authors describe a 5-year-old boy with beta-thalassemia major who received bone marrow transplantation (BMT) from a human leukocyte antigen (HLA)-matched unrelated donor. The conditioning regimen consisted of 16 mg/kg busulfan and 200 mg/kg cyclophosphamide. The transplantation was complicated with grade II graft-versus-host disease, although prophylaxis with cyclosporine and short-term methotrexate was carried out. Cytomegalovirus disease occurred at 2 months after transplantation but was controlled successfully. The child remains disease-free and in good clinical condition 53 months after BMT. The authors suggest that BMT from an HLA-matched unrelated donor could be considered as an alternative treatment in patients with beta-thalassemia major when no HLA-matched donor is available.