二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性

目的 探讨应用二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性.方法 回顾性分析1999年10月-2010年3月在北京大学血液病研究所接受二次造血干细胞移植作为挽救治疗的25例移植后复发患者的资料.除1例移植前未达缓解状态的患者外,其余24例患者在第1次移植后的中位8.8(1～55)个月出现复发,经过中位3(0.3～20)个月的治疗,接受了二次移植.2次移植中位间隔10.6(0.6～59.0)个月.结果 25例患者预处理方案主要为含全身放疗(TBI)或改良的BUCY(马利兰+环磷酰胺)方案.全部患者达到白细胞植活标准,并生存超过30 d,有3例患者发生肝窦阻塞综合征,放射性皮炎以及急性心肌梗死等严重预处理相关毒性,但经治疗后均恢复.截至2011年1月,经过中位9.1(2.0～131.1)个月的随访,8例患者生存,总的生存率为30.9%.12例患者复发,复发率55.7%,复发中位时间是二次移植后的4.4(1.0～8.5)个月.7例患者因移植相关合并症死亡,非复发病死率35.1%.单因素分析发现患者二次移植时是否缓解与生存期有显著关联(P=0.009).结论 适度降低强度的预处理方案可以使二次异基因造血干细胞移植安全地应用于移植后复发的患者,保证移植物的植入,非复发病死率亦在可接受范围内.     

二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性

目的 探讨应用二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性.方法 回顾性分析1999年10月-2010年3月在北京大学血液病研究所接受二次造血干细胞移植作为挽救治疗的25例移植后复发患者的资料.除1例移植前未达缓解状态的患者外,其余24例患者在第1次移植后的中位8.8(1～55)个月出现复发,经过中位3(0.3～20)个月的治疗,接受了二次移植.2次移植中位间隔10.6(0.6～59.0)个月.结果 25例患者预处理方案主要为含全身放疗(TBI)或改良的BUCY(马利兰+环磷酰胺)方案.全部患者达到白细胞植活标准,并生存超过30 d,有3例患者发生肝窦阻塞综合征,放射性皮炎以及急性心肌梗死等严重预处理相关毒性,但经治疗后均恢复.截至2011年1月,经过中位9.1(2.0～131.1)个月的随访,8例患者生存,总的生存率为30.9%.12例患者复发,复发率55.7%,复发中位时间是二次移植后的4.4(1.0～8.5)个月.7例患者因移植相关合并症死亡,非复发病死率35.1%.单因素分析发现患者二次移植时是否缓解与生存期有显著关联(P=0.009).结论 适度降低强度的预处理方案可以使二次异基因造血干细胞移植安全地应用于移植后复发的患者,保证移植物的植入,非复发病死率亦在可接受范围内.     

二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性

目的 探讨应用二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性.方法 回顾性分析1999年10月-2010年3月在北京大学血液病研究所接受二次造血干细胞移植作为挽救治疗的25例移植后复发患者的资料.除1例移植前未达缓解状态的患者外,其余24例患者在第1次移植后的中位8.8(1～55)个月出现复发,经过中位3(0.3～20)个月的治疗,接受了二次移植.2次移植中位间隔10.6(0.6～59.0)个月.结果 25例患者预处理方案主要为含全身放疗(TBI)或改良的BUCY(马利兰+环磷酰胺)方案.全部患者达到白细胞植活标准,并生存超过30 d,有3例患者发生肝窦阻塞综合征,放射性皮炎以及急性心肌梗死等严重预处理相关毒性,但经治疗后均恢复.截至2011年1月,经过中位9.1(2.0～131.1)个月的随访,8例患者生存,总的生存率为30.9%.12例患者复发,复发率55.7%,复发中位时间是二次移植后的4.4(1.0～8.5)个月.7例患者因移植相关合并症死亡,非复发病死率35.1%.单因素分析发现患者二次移植时是否缓解与生存期有显著关联(P=0.009).结论 适度降低强度的预处理方案可以使二次异基因造血干细胞移植安全地应用于移植后复发的患者,保证移植物的植入,非复发病死率亦在可接受范围内.

Abstract：

Objective To investigate the safety and efficacy of second allogeneic hematopoietic stem cell transplantation for the relapsed hematologic malignancies. Methods The data of 25 relapsed patients received the second allogeneic transplantation as a salvage therapy in Institute of Hematology Peking University between October 1999 and March 2010 were analyzed retrospectively. Twenty-four patients relapsed at 8. 8 (1-55) months after the first transplantation, except one received the second transplantation as prophylaxis therapy. They received the second transplantation after 3(0. 3-20) months' therapy. The median time between the 2 transplants was 10. 6(0. 6-59. 0) months. Results Most of the patients were given the conditioning regimen including total body irradiation (TBI, 700-779 cGy) or modified busulfan and cyclophosphamide (BUCY, BU 12 mg). All patients survived more than 30 days and achieved sustained white blood cell engraftment. Sinus obstructive syndrome, irradiation dermatitis and acute myocardial infraction were occurred in 3 patients and recoverable. Until January 31 in 2011, with a median observation period of 9. 1 (2. 0-131. 1) months, 8 patients had been living with a overall survival (OS) of 30.9%.Twelve patients relapsed at a median 4. 4 months and 10 died of it. The other 7 patients died of transplant related complications. The non-relapsed mortality was 35. 1 %. The disease status at the 2nd transplantation was the only factor which effected the OS (P = 0. 009). Conclusions The second allogeneic transplantation is a viable option for patients relapsing after the first transplantation. Reduced intensive conditioning regimen ensures the graft engraftment and reduces transplant related toxicity.     

11例白血病异基因造血干细胞移植后复发行二次移植的临床研究

目的:研究第二次异基因造血干细胞移植(allo-HSCT)治疗白血病的疗效,探讨如何提高二次移植的成功率。方法:总结本院2012—2019年11例因allo-HSCT后复发行第二次allo-HSCT(更换供者)的急性白血病患者的临床资料,回顾性分析其治疗过程及转归,并分析二次移植前患者的缓解状态、供者选择、预处理方案等对总生存、无病生存、复发死亡率、移植相关死亡率等移植疗效的影响。结果:11例患者在二次移植后均获得早期缓解,随访至今,2例患者无病存活,存活时间分别为9个月、18.4个月,2例患者因移植后合并症(血栓性微血管病/肺部移植物抗宿主病)死亡,7例患者因复发死亡。其中早期死亡(移植后3个月内)2例,二次移植至死亡中位时间为9个月(2～48个月)。11例患者二次移植后中位总生存期11个月(2～18.4个月),中位无病生存期6个月(1～18.4个月),复发死亡率63.6%,移植相关死亡率18.2%。结论:二次移植是治疗allo-HSCT后复发的一种有效手段,部分患者可获得长久无病生存,但二次移植合并症多、复发率高,需要慎重考虑,强化预处理、更换供者、缓解期行二次移植被认为是提高二次移植疗效的可能手段。     

FABC预处理异基因造血干细胞移植治疗难治未缓解急性白血病临床研究

目的观察FABC预处理异基因造血干细胞移植治疗未缓解急性白血病(AL)患者的疗效及安全性。方法收集2005年11月至2010年8月广东省人民医院采用FABC预处理方案进行异基因造血干细胞移植治疗18例难治未缓解AL患者。观察造血恢复、植入率、急慢性移植物抗宿主病发生率、移植相关病死率、复发、总存活率和无病存活率及预后因素分析。结果所有患者均于移植后14～21 d获得完全供者植入,中性粒细胞>0.5×109/L和血小板>20×109/L中位时间分别为12(7～72)d和13(7～60)d;急性移植物抗宿主病(GVHD)及慢性GVHD累积发生率分别为50%和73.3%。中位随访10.5(3.1～66.6)个月,移植相关病死率5.6%(1/18),复发率为36.8%(7/18)。1年的预期总生存(OS)率和无病生存(DFS)率分别是(58.9±13.2)%和(53.6±15.5%)。COX逐步回归模型分析显示,慢性GVHD是DFS独立有利因素。结论 FABC预处理异基因造血干细胞移植是治疗难治性未缓解AL安全有效的方法。     

造血干细胞移植后女性性激素水平与预后随访分析

目的初步探索造血干细胞移植后女性性激素水平及生育情况, 及其与预处理方案的相关性, 并分析移植后年轻女性激素替代治疗的效果。方法回顾性病例系列研究。选取2010年1月至2021年1月在苏州大学附属第一医院接受造血干细胞移植后进行性激素水平检测随访的147例女性患者的临床资料, 分析随访患者的生存、月经及生育情况, 激素替代治疗情况, 检测移植后患者性激素水平, 评估患者卵巢功能。采用独立样本t检验、χ2检验等进行组间比较。结果 147例患者年龄10～45岁, 中位年龄26岁, 异基因造血干细胞移植135例, 自体造血干细胞移植12例;129例接受清髓性预处理, 18例接受减低剂量预处理。随访18～134个月, 中位数为50个月, 5例患者因疾病复发而死亡。54例预处理前使用醋酸戈舍瑞林的患者中3例移植后自行恢复月经, 均为清髓性预处理患者;1例通过辅助生殖技术分娩双胎。93例预处理前未使用醋酸戈舍瑞林的患者中2例自行恢复月经, 均为再生障碍性贫血非清髓性预处理, 并自然受孕。接受清髓性预处理的患者移植后卵泡刺激素水平显著高于接受减低剂量预处理的患者[(95.28±3.94)U/L比(7...     

自体造血干细胞移植治疗多发性骨髓瘤的疗效分析

目的:评价自体造血干细胞移植(APBSCT)治疗多发性骨髓瘤(MM)的临床疗效。方法:对25例Durie-Salmon分期为ⅡA~ⅢB期的MM患者行化疗联合APBSCT,其中5例患者预处理方案中在马法兰基础上加用硼替佐米,随访分析移植后反应率及生存情况。结果:25例患者均获得造血重建,中性粒细胞植入中位时间为15(8~26)d,血小板植入中位时间为22(11~50)d,移植相关并发症包括发热9例,其中肺部感染4例,移植相关病死率为0。25例患者均于移植后1个月全面评估,16例(64%)达到完全缓解,5例(20%)达到非常好的部分缓解,4例(16%)达到部分缓解,总体有效率为100%。中位随访30(2~70)个月,8例复发,其中3例经二次移植后达到完全缓解,5例经再次诱导后获得完全缓解。最终4例死于肺部感染。25例移植后中位无进展生存期为42个月。结论:APBSCT是治疗MM相对有效和安全的方法,鉴于前期诱导及移植前预处理方案中加入硼替佐米的优越性尚需进一步探讨。     

含全身照射预处理方案行HLA不相合非去T造血干细胞移植治疗白血病8例临床分析

目的探讨采用全身照射(TBI)预处理方案行人类白细胞抗原(HLA)配型不相合亲缘供者非去T异基因造血干细胞移植(allo-HSCT)治疗白血病的疗效。方法2002年4月至2007年1月北京大学血液病研究所8例采用TBI预处理方案行HLA不合非去T亲缘供者allo-HSCT的白血病患者,其中急性髓性白血病(AML)3例,急性淋巴细胞性白血病(ALL)4例,慢性粒细胞白血病1例;预处理方案采用TBI加环磷酰胺(CY)方案4例,TBI加氟达拉滨(FLU)方案4例;干细胞来源包括骨髓和外周血造血干细胞移植6例,外周血造血干细胞移植(PBSCT)2例;移植物抗宿主病(GVHD)预防采用经典的环孢素A(CsA) 霉酚酸酯(MMF) 短程甲氨蝶呤(MTX)方案。结果8例供者采集单个核细胞(MNC)中位数为7.39(6.27~12.46)×108/kg,粒细胞植入中位时间11(11~13)d,血小板植入中位时间13(11~21)d。5例发生Ⅰ~Ⅱ度急性GVHD,2例出现慢性广泛性GVHD,无严重急性GVHD或因GVHD死亡病例。中位随访时间9(3~53)个月,除1例复发存活外,其余病例无病存活。结论对于HLA不相合异基因造血干细胞移植,TBI方案是一种比较安全、有效的非去T预处理方案,对于高危和二次移植患者同样有效。     

“马利兰+阿糖胞苷+环磷酰胺”预处理方案行外周血造血干细胞移植治疗白血病的疗效观察

目的探讨使用"马利兰+阿糖胞苷+环磷酰胺"(MAC)预处理方案行外周血造血干细胞移植(PBSCT)治疗白血病的临床疗效。方法对我院10例PBSCT治疗的急性白血病患者的临床资料进行分析,预处理采用MAC方案,临床观察药物的不良反应并评估造血重建速度及患者预后。结果 10例患者获得造血重建,未发生预处理相关死亡。移植后5～7d白细胞降为0,中性粒细胞绝对数>0.5×109/L的中位时间为11(8～12)d,无输注血小板计数>20×109/L的中位时间为13(12～13)d;本组平均随访36.8个月(3～100个月),其中3例(30%)患者移植后3个月左右复发。所有患者在移植过程中未出现严重不良反应。结论 MAC预处理方案其不良反应小,优于经典的全身照射/CY方案,且简便易行,抗白血病作用确实可靠,是治疗恶性血液病安全有效的方法。     

地西他滨联合异基因造血干细胞移植治疗慢性粒-单核细胞白血病的临床研究

目的:对临床上使用地西他滨联合异基因造血干细胞移植治疗慢性粒-单核细胞白血病(CMML)患者进行回顾性研究。方法:对2014—2020年在苏州大学附属第一医院血液科接受地西他滨治疗并进行异基因造血干细胞移植的18例CMML患者进行回顾性分析,评价其总生存率,无白血病生存率,累积复发率及治疗相关死亡率等指标,观察18例患者植入、移植物抗宿主病(GVHD)、复发及生存情况。同时根据患者预处理方案中是否桥接地西他滨,将患者分为地西他滨桥接改良BU/CY预处理组和其他预处理方案组,比较以上指标。结果:(1)纳入18例CMML患者(男13例,女5例),中位年龄31(13～52)岁;10例患者仅在移植前病程中接受地西他滨治疗,采用改良BU/CY及其他预处理方案,8例患者采用地西他滨桥接改良BU/CY预处理方案;其中无关全相合移植1例,亲缘全相合移植5例,亲缘单倍体移植12例。(2)18例患者均获得供者型植入,粒系植入中位时间14(11～21) d,巨核系中位植入时间20(9～40) d,2组预处理方案间粒系植入时间、巨核系植入时间差异无统计学意义。(3)13例患者发生急性GVHD,总发生率为72.2%(95%CI 49.3～95.1);Ⅲ～Ⅳ度急性GVHD 7例,发生率为38.9%(95%CI 13.9～63.8);2组预处理方案间急性GVHD的发生率差异无统计学意义(P0.05)。(4)18例患者中共有9例死亡,3例为复发相关死亡,3年累积复发率为17.3%±0.9%,中位复发时间157(104～406) d;6例为移植相关死亡,3年移植相关死亡率为33.3%±1.3%。(5)3年总生存率为55.6%±11.7%,3年无白血病生存率为49.4%±11.9%,2组预处理方案间总生存率和无白血病生存率差异无统计学意义(P0.05)。结论:含地西他滨的预处理方案桥接异基因造血干细胞移植治疗CMML是安全可行的。     

Second autologous stem cell transplant for multiply relapsed Hodgkin's disease

Therapeutic options for patients with Hodgkin's disease who relapse after high-dose chemotherapy with autologous stem cell support are limited. Salvage chemotherapy is not curative, and allogeneic stem cell transplantation in this setting is associated with mortality rates of 40-65%. We report our institution's experience with second autologous transplants in this patient population. Five patients (median age 36) with relapsed Hodgkin's disease underwent a second autologous stem cell transplant at a median of 66 months after first transplant. Four patients received CBV, and one patient received BuCy as conditioning. Neutrophil and platelet engraftment occurred by days +10 and +16, respectively. All patients achieved a complete response, and no relapses have occurred after a median follow-up of 42 months. All four patients who received CBV developed interstitial pneumonitis, and two patients died of pulmonary complications 37 and 48 months following second transplant. Three patients remain alive and disease-free 41, 42 and 155 months after second transplant. These data indicate that second autologous transplantation should be considered for selected patients who relapse after a prolonged response to first autologous transplant. However, BCNU pneumonitis is the major toxicity in patients who have undergone previous mantle radiation and received busulfan with first transplant.     

Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant

Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count >0.5 x 10(9)/l and to platelet count of >20 x 10(9)/l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more beneficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.     

Allogeneic bone marrow transplantation for children with histiocytic disorders: use of TBI and omission of etoposide in the conditioning regimen

The histiocytoses are rare disorders of antigen-processing phagocytic or antigen-presenting cells. Allogeneic bone marrow transplantation (BMT) can be curative of these disorders. We report a series of five children with Langerhans cell histiocytosis (n=2) or hemophagocytic lymphohistiocytosis (n=3), who received allogeneic BMT with a total body irradiation (TBI)-containing regimen (TBI, cytarabine, and cyclophosphamide) at our institution between 1995 and 2000. One of these patients received busulfan, cyclophosphamide, and etoposide for the first of two BMTs. All grafts except one (a matched sibling-donor graft) were T-cell-depleted grafts from unrelated donors. All received cyclosporine graft-versus-host disease (GvHD) prophylaxis; the recipient of the matched sibling graft also received methotrexate. Three patients engrafted at a median of 24 days after transplantation. The patient who did not receive TBI experienced primary graft failure and recurrent disease. After the TBI-containing conditioning regimen was given, a second transplant engrafted on day +17. One patient with concurrent myelodysplastic syndrome died of toxicity on day +33 without evidence of engraftment. No acute or chronic GvHD was observed. Four patients survive disease-free, a median of 63 months after transplantation, all with Lansky performance scores of 100. We conclude that a conditioning regimen containing TBI but not etoposide is effective in allogeneic BMT for children with histiocytic diseases.     

Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation

We describe treatment, outcomes and prognostic factors for patients who relapse following transplantation with a reduced intensity conditioning regimen. Seventy consecutive patients with high-risk myeloid malignancies underwent transplant and 25 (36%) relapsed, a median of 120 days later. The median percentage of bone marrow blasts at relapse was 24, the median donor chimerism was 73% and new karyotypic abnormalities occurred in 8 out of 20 (40%) evaluable patients. Twenty-one patients (84%) received aggressive treatment for relapse, including chemotherapy (60%), second hematopoietic cell transplantation (HCT; 52%) and/or donor lymphocyte infusion (DLI; 12%). Thirteen achieved a complete response (CR) and four remain in CR. Median overall survival (OS) after relapse was 6 months (95% confidence interval=2.7-9.9 months), and actuarial 1 year OS was 24%. Most deaths were due to disease progression (17/20, 85%). We did not observe an advantage for cellular therapy (DLI or second transplant) compared to chemotherapy. Salvage therapy for relapse after reduced intensity HCT is feasible, associated with low treatment-related mortality, and may result in prolonged survival in select patients. Studies exploring the optimal treatment for relapse following reduced intensity HCT are warranted.     

Fludarabine/melphalan conditioning for allogeneic transplantation in patients with multiple myeloma

The purpose of the study was to determine the feasibility and efficacy of a reduced intensity conditioning regimen of fludarabine and melphalan for allogeneic transplantation in patients with multiple myeloma. From August 1996 to December 2000, 22 patients received a reduced intensity conditioning regimen with fludarabine and melphalan. Median age was 51 years (range, 45-64), median time from initial therapy to transplant was 36 months (range, 3-135 months). Disease phase prior to transplant was primary refractory in two patients, refractory relapse in 11 patients, sensitive relapse in eight patients and initial remission consolidation in one patient. The median number of prior therapies was five (range, 1-7), and median beta 2 microglobulin prior to transplant was 3.0 mg/l (range, 1.0-7.3). All patients received unmanipulated grafts from either HLA matched sibling donors (n = 13) or matched unrelated donors (n = 9). Eighteen patients received fludarabine 30 mg/m(2) for 4 days with melphalan 140 mg/m(2) as a single dose and four patients received fludarabine 25 mg/m(2) for 5 days with melphalan 90 mg/m(2) daily for 2 days. All 21 patients evaluable for engraftment achieved a neutrophil count of >0.5 x 10(9)/l after a median of 12 days (range, 9-24), 18 patients achieved platelet transfusion independence after a median of 14 days (range, 8-47). All engrafting patients had 100% donor cell engraftment. Seven patients achieved a complete remission. Six patients are currently alive with a median follow-up of 15 months (range, 10-47 months). The actuarial survival and progression-free survival is 30 +/- 11% and 19 +/- 9% at 2 years. Non-relapse mortality at 100 days was 19 +/- 10% and 40 +/- 10% at 1 year. Fludarabine/melphalan combinations are feasible and allow consistent engraftment of allogeneic progenitor cells from both related and unrelated donors in patients with multiple myeloma and should be explored in patients with less advanced disease.     

Haplotype mismatched transplantation using high doses of peripheral blood CD34+ cells together with stratified conditioning regimens for high-risk adult acute myeloid leukemia patients: a pilot study in a single Korean institution

A total of 11 high-risk Korean acute myeloid leukemia (AML) patients received stem cell transplantation from human leukocyte antigen (HLA) haploidentical donors. Specifically, for eight patients with 2-3 mismatched antigens and bidirectional vectors, we used a newly designed conditioning regimen that consists of total body irradiation, busulfex, ATG, and fludarabine. The median number of CD34+ cells infused was 15.4 x 10(6)/kg (range, 8-21.2). These patients received neither graft-versus-host disease (GvHD) prophylaxis nor post transplantation G-CSF. All of the patients who were followed up for a median of 6 months (range, 17 days-28 months) showed stable primary engraftment and had no acute GvHD or transplant-related mortality for 100 days post transplant. Three patients with high-risk or refractory disease eventually died in relapse, even with GvH-directed NK alloreactivity. However, the patients in complete remission (CR), with the exception of one patient who is alive at 18 months EFS, died at 4, 6, and 8 months post transplantation due to infections that were associated with delayed immune recovery. Our findings suggest that haploidentical transplantation represents a feasible treatment for patients with high-risk AML in CR, provided that a plan for the enhancement of immune recovery is implemented.     

Dose intensification with autologous stem cell transplantation in relapsed and resistant Hodgkin's disease

BACKGROUND AND OBJECTIVES: Patients affected by Hodgkin's disease (HD) resistant to induction therapy or who have a brief duration of first remission have a poor outcome. DESIGN AND METHODS: We retrospectively reviewed the clinical data of 28 patients affected by Hodgkin's disease who relapsed 6 to 24 months from completion of treatment (14 patients) or who were refractory to first-line therapy or relapsed very early (14 patients). All the 28 patients were treated with salvage chemotherapy plus a conditioning regimen followed by peripheral blood stem cell transplant (PBCST) or autologous bone marrow transplant (ABMT). RESULTS: At a median follow-up of 35.5 months (range 14-119), of the 14 patients responding to first-line therapy but who relapsed > 6 months off therapy, 10 (72%) are alive, well and in complete remission (CR), 2 (14%) are alive with disease at 39 and 83 months from transplant, and 2 (14%) died 26 and 63 months after their transplant from acute myeloid leukemia and HD, respectively. At a median follow-up of 39 months, the overall survival (OS) is 68% and the event-free survival (EFS) is 56%. At a median follow-up of 30 months (1-98), of the 14 patients refractory to first-line therapy or who relapsed very early, 9 (64%) are alive in CR, 1 (7%) is alive with disease and 4 (29%) have died of their disease (3 patients) or myelodysplastic syndrome (1 patient). The OS is 58% and the EFS is 52%. There are no statistically significant differences in terms of OS and EFS between the two groups of patients. INTERPRETATION AND CONCLUSIONS: Our study shows that salvage chemotherapy followed by a conditioning regimen and autotransplant is an effective, feasible and well-tolerated scheme of therapy not only for patients with HD who relapse after first-line treatment, but also for those resistant to first-line treatment.