Mitoxantrone, etoposide, carboplatinum and ara-C combination therapy (MECA) in refractory and relapsed acute leukemia

The present study was undertaken to assess the feasibility, toxicity and antileukemic activity of sequential chemotherapy including mitoxantrone, etoposide, carboplatin and intermediate-dose cytarabine in adult patients with refractory and relapsed acute myelogenous (AML) or lymphoid (ALL) leukemia. Fifty-one patients with poor-risk AML and ALL received 64 courses of MECA therapy. The overall response in the entire group was 51% (43% complete remission). The stage of the disease (relapsed or primarily refractory) and the age of the patients did not strongly affect the response rate. MECA therapy was more effective in ALL than in AML, and in those patients who presented at salvage treatment with a bone marrow infiltration lower than 25% blasts. Hematological and extra-hematological toxicities were tolerable and there were 6 deaths related to the treatment (11%). The incidence of documented infectious episodes was 71%. MECA therapy is a safe treatment and has a high antileukemic activity in relapsed and primarily refractory AML or ALL.     

Etoposide in combination with intermediate dose cytosine arabinoside (ID ARA C) given with the intention of further myeloablative therapy for the treatment of refractory or recurrent hematological malignancy.

Thirty-four patients with refractory or recurrent high grade non-Hodgkin's lymphoma (NHL) or acute leukemia were treated with a combination of etoposide, 100 mg/m2 daily, and ara C, 1 g/m2 twice daily, for 5 days (VPARAC). This therapy was given in the anticipation that remissions thus achieved would be 'consolidated' with myeloablative therapy supported by bone marrow transplantation (BMT). The complete remission rate (CR) in patients with NHL was 3/18 (17 per cent) with partial responses (PR) seen in a further four patients, giving an overall response rate of 39 per cent. Four patients (three in CR, one in PR) proceeded to the planned consolidation treatment. Complete remission was achieved in 2/8 (25 per cent) patients with acute myelogenous leukemia (AML) and in 2/8 patients with acute lymphoblastic leukemia (ALL). Three of these patients subsequently had myeloablative consolidation therapy with BMT. There were four treatment-related deaths (NHL, two; AML, one; ALL, one). In poor risk patients with high grade NHL and acute leukemia, VPARAC is an effective remission induction programme in 21 per cent of patients. Seven of the original 34 patients received the intended 'curative' therapy, of whom only four are alive and well 1 year later.     

短程大剂量盐酸米托蒽醌与阿糖胞苷治疗难治复发急性白血病的临床研究

目的 :评价大剂量盐酸米托蒽醌 40 mg/ m2单剂与阿糖胞苷 (1～ 1.5 ) g/ m2连用 5 d,治疗难治复发急性白血病的疗效及推广应用价值。方法 :以该方案对 2 0例难治复发急性白血病进行 2 2例次治疗。结果 :2 2例次治疗中的 2 0例次获得完全缓解 (CR90 .9% ) ,1例次取得部分缓解 (PR4.5 4% ) ,其中 14例急淋的 16例次治疗 ,14例次取得完全缓得 ,1例次部分缓解 ,1例无效 ,6例急性粒细胞白血病治疗均取得完全缓解 ,无治疗相关死亡。结论 :短程大剂量米托蒽醌联合阿糖胞苷对难治复发急性白血病有较高的疗效 ,可提高缓解率 ,降低死亡率。     

CLAG方案治疗复发难治急性髓系白血病的疗效观察

目的:评价CLAG方案（2-CdA+Ara-C+G-CSF）治疗复发难治急性髓系白血病的疗效及安全性。方法:回顾性分析我中心2015年6月至2016年8月应用CLAG方案治疗的12例复发难治急性髓系白血病患者。结果:12例患者均系复发难治急性髓系白血病,根据NCCN急性髓系白血病指南（2017年第1版）细胞遗传学及分子生物学标记,进行危险度分级,其中预后良好组3例,预后中等组5例,预后不良组4例。所有患者均给予1疗程CLAG方案化疗,其中8例（72.7%）达到完全缓解（CR）,2例（18.2%）达到部分缓解（PR）,总有效率（OR）90.9%。所有患者均出现Ⅲ-Ⅳ级血液学毒性,主要毒副反应为粒细胞缺乏及血小板减少所导致的感染和出血,其中肺部感染8例（72.7%）,侵袭性真菌病5例（45.5%）,革兰阴性杆菌败血症2例（18.2%）。6例患者（54.5%）发生Ⅲ-Ⅳ级出血,1例因弥漫性肺泡出血早期死亡。化疗所致恶心呕吐、肝肾毒性、口腔黏膜炎等非血液学毒性均为Ⅰ-Ⅱ级。结论:CLAG方案治疗复发难治性急性髓系白血病有效率较高。化疗所致骨髓抑制较重,但合并感染、出血可控制,非血液学毒性轻微,安全性较好,可作为复发难治急性髓系白血病挽救性治疗的首选方案。     

替尼泊苷联合方案治疗交叉表达双系相关抗原急性白血病的临床研究

目的 :探讨替尼泊苷联合方案治疗交叉表达淋系和髓系抗原急性白血病的化疗疗效。方法 :应用替尼泊苷联合阿糖胞苷、环磷酰胺、长春地辛及泼尼松组成 TA或 TA+COP方案 ,治疗伴淋系抗原表达的急性髓细胞白血病 (L y+ AML) 2 4例和伴髓系抗原表达的急性淋巴细胞白血病(My+ AL L) 1 7例。结果 :完全缓解 (CR)率为 5 6 .1 % (2 3/ 4 1 ) ,总有效率为 80 .5 % (33/ 4 1 )。与常规方案 (DA、VDL P)诱导疗效相比有显著性差异 (P<0 .0 1 )。其中 L y+ AML 的 CR率为 5 8.3% ,总有效率为 79.2 % ;My+ AL L 的 CR率为 5 2 .9% ,总有效率为 82 .4 %。复治性 L y+ AML / My+ AL L 总有效率为 72 .7% (8/ 1 1 )。两种方案的骨髓抑制明显 ,毒副作用能够耐受。结论 :L y+ AML 和 My+ AL L不宜采用常规诱导缓解方案 ,TA和 TACOP方案宜作为此类患者的首选治疗方案     

Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients

Clofarabine is a promising new chemotherapeutic agent that is active in the treatment of pediatric acute leukemia. Forty children (16 with acute myeloid leukemia [AML], 24 with acute lymphoblastic leukemia [ALL]), aged 1-20 years (median 7.6 years) with relapsed or refractory ALL or AML were treated because of resistance to first-line treatment (n =5), or for first (n =22), second (n =11) or third relapse (n =2). They received clofarabine (40 mg/m(2)/day) associated with etoposide (100 mg/m(2)/day) and cyclophosphamide (440 mg/m(2)/day) administered as one or two induction cycles (5 days of chemotherapy) in an attempt to reach complete remission (CR) or CR without platelet recovery (CRp). This was followed by 1-3 consolidation cycles (4 days of chemotherapy) for a maximum of four cycles. Seven (44%) out of 16 and 10 (42%) out of 24 evaluable children with AML and ALL, respectively, responded to treatment. The most common adverse events were infections and gastrointestinal and hepatic toxicity. Thirteen (76%) out of 17 responders underwent hematopoietic stem cell transplant. The 24-month overall survival was 25%, while it was 59% among patients who responded to the first induction cycle. Our study suggests that this drug regimen is well tolerated and can be effective in heavily pretreated pediatric patients with relapsed or refractory acute leukemia.     

米托蒽醌联合治疗儿童难治性复发性急性白血病的临床疗效观察

 目的 观察总结米托蒽醌（MTZ）联合治疗儿童难治性复发性急性白血病（RRAL）的疗效。方法 RRAL 12例,急性淋巴细胞白血病（ALL）9例,急性髓性白血病（AML）3例;ALL用VMLP／Dex方案（长春新碱、米托蒽醌、左旋门冬酰胺酶、泼尼松／地塞米松）2～4周;AML用MAE方案（米托蒽醌、阿糖胞苷、依托泊苷）或大剂量阿糖胞苷+依托泊苷。结果 9例ALL,CR 7例,PR 1例,1例未复查;3例AML,CR 2例,NR 1例。总CR率为81.8 %（9／11）,总有效率90.9 %（10／11）。用药后骨髓抑制较明显,大部分病例ANE≤0.1×109／L持续1～2周,轻微肝功能损害,未见药物相关的心脏损害。结论 MTZ不失为治疗儿童难治性复发性急性白血病的有效药物之一,用药后要注意预防和治疗骨髓抑制后出现的各种感染和出血。     

Oral Idarubicin and Low Dose Cytarabine as the Initial Treatment of Acute Myeloid Leukemia in Elderly Patients

Idarubicin (IDR) is an anthracycline that can be administered orally. Low dose cytarabine (LDARAC) has been commonly used in the treatment of acute myeloid leukemia (AML) in elderly patients. A comination of oral IDR (20 mg/m² for 3 days) and LDARAC (10 mg/m² q12 hours for 10 days) was given in 32 patients aged 65 to 82 years (median 76) with de novo AML. Eight patients whose marrow remained blastic by day 20 received a second course (IDR for 2 days and LDARAC for 5 days). Complete remission (CR) was achieved in 13 cases (40.5%), (one course 12, two courses 1). There was 1 early death, 3 deaths in aplasia, 2 partial remissions and 13 failures. All but 5 patients were entirely managed in hospital. The median duration of neutropenia was 18 days and only 1 patient obtained CR without therapeutic aplasia. The extrahematologic toxicity was mild with 3 reversible cardiac events. These results are comparable to those obtained with conventional chemotherapy and this regimen could be proposed as induction treatment of AML in elderly patients.     

Oral idarubicin and low dose cytarabine as the initial treatment of acute myeloid leukemia in elderly patients

Idarubicin (IDR) is an anthracycline that can be administered orally. Low dose cytarabine (LDARAC) has been commonly used in the treatment of acute myeloid leukemia (AML) in elderly patients. A comination of oral IDR (20 mg/m(2) for 3 days) and LDARAC (10 mg/m(2) q12 hours for 10 days) was given in 32 patients aged 65 to 82 years (median 76) with de novo AML. Eight patients whose marrow remained blastic by day 20 received a second course (IDR for 2 days and LDARAC for 5 days). Complete remission (CR) was achieved in 13 cases (40.5%), (one course 12, two courses 1). There was 1 early death, 3 deaths in aplasia, 2 partial remissions and 13 failures. All but 5 patients were entirely managed in hospital. The median duration of neutropenia was 18 days and only 1 patient obtained CR without therapeutic aplasia. The extrahematologic toxicity was mild with 3 reversible cardiac events. These results are comparable to those obtained with conventional chemotherapy and this regimen could be proposed as induction treatment of AML in elderly patients.     

Sequential combination of high dose ARA-C (HiDAC) and asparaginase (ASP) for the treatment of advanced acute leukemia and lymphoma

Thirty patients with advanced acute leukemia and lymphoma were treated with the sequential combination of high dose ARA-C (HiDAC 3 gm/m2 infused i.v. over 3 h at 0, 12, 24, 36 h) and asparaginase (ASP 6.000 IU/m2 i.m. at hour 42). The sequence was given on day 1 and 8 irrespective of the degree of myelosuppression. Of 22 patients with leukemia there was only one who was absolutely refractory to therapy. Complete remission was induced in 3 patients with ANLL (30%) and in 3 with ALL (30%). Three patients became hypoplastic but recovered with blasts and 12 died from infection, complicated by intracranial hemorrhage in 3, during hypoplasia. Of 8 patients with lymphoma, 2 were clearly refractory to therapy, one died from sepsis and the remaining 5 all entered remission (2 CR + 3 PR, 62%). Activity of HiDAC/ASP against CNS disease is suggested by the clinical response seen in patients with overt meningeal or intracerebral involvement. Toxicity associated with HiDAC/ASP was mainly hematologic. All but one patient experienced hypoplasia and severe pancytopenia; documented infections and major hemorrhages occurred in 80 and 20% of patients respectively. We conclude that HiDAC/ASP is a regimen with definite activity against acute leukemia and lymphoma including CNS disease. Alternate treatment schedules should be explored in order to reduce marrow toxicity.     

Causes of death--other than progressive leukemia--in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML): the Dutch Childhood Oncology Group experience.

We analyzed causes of death, other than resistant disease or relapse, in 875 children with acute lymphoblastic leukemia (ALL) and 229 with acute myeloid leukemia (AML), treated on three different Dutch Childhood Oncology Group (DCOG) ALL and three AML protocols. Overall, 23 (2.6%) ALL and 44 (19.2%) AML patients died. Early death (ED, before remission was reached) occurred in nine ALL (1%) and thirty AML (13.1%) patients, including three and ten deaths before treatment was initiated. Chemotherapy-related mortality in remission (CRM) occurred in nine ALL (1.1%) and eight AML (4.4%) patients. For ALL, both ED and CRM declined over time, although this was not statistically significant. For AML a decrease in ED was observed (from 26% to approximately 10%), but counter-balanced by an increase in CRM (from 3 to 8%), maybe related to the scheduling of intensification blocks in AML-92/94. Including transplant-related mortality, death in CR rates in AML increased from 3 to 15% in the last study. The main cause of ED was hemorrhage, often associated with hyperleucocytosis, and infection for CRM. We conclude that mortality dropped favorably in ALL, but not in AML. Especially for AML, effective but less toxic therapy and better supportive care guidelines need to be developed.     

Carboplatin plus cytarabine in the treatment of high-risk acute myeloblastic leukemia.

Thirty-one patients (20 male and 11 female; median age 51 years (16-79)) with high-risk acute myeloblastic leukemia (AML) (20 refractory AML and 11 secondary AML (s-AML) (four to myelodysplastic syndrome, five to chemo/radiotherapy, one to aplastic anemia and one blastic chronic myelogenous leukemia (B-CML)) were treated with CBDCA (300 mg/m2/day x 5 days in continuous i.v. infusion) plus intermediate-dose Ara-C (500 mg/m2/day x 3 days in rapid i.v. infusion). Nine patients (29%) achieved CR (five s-AML (three myelodysplastic syndromes, one CML and one ALL) and four refractory AML) and 11 patients had resistant disease. There were 11 early deaths (35%). Median disease-free survival of the nine responders was 4 months. The main toxicity was hematological, febrile episodes took place in nearly all the patients (96%). The CBDCA plus Ara-C regimen showed an evident antileukemic activity in high-risk leukemia. However, the lack of long-term disease-free survivors shows the need for innovative postremission strategies. The high initial response rate seen in AML secondary to myelodysplastic syndromes (MDS) warrants further investigation of CBDCA in combination regimens for MDS patients.     

Fludarabine and cytarabine as a sequential infusion regimen for treatment of adults with recurrent, refractory or poor prognosis acute leukemia

We did a retrospective analysis on the safety and efficacy of sequential infusion fludarabine and cytosine arabinoside (ara-C) in treating refractory, recurrent or poor prognosis acute leukemia in adult patients. Forty-five adult patients with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) received a total of 68 courses of sequential continuous infusion of fludarabine for 2 days (total dose 71.5 mg/m(2) ) followed by 3 days of ara-C (total dose 7590 mg/m(2) ). Thirty-nine patients had refractory or recurrent disease, and six had other adverse prognostic features. Thirty-six patients had AML, seven had ALL, and two had CML in blastic phase. Complete remission was seen in 20 patients (44%), and partial remission in 5 patients (11%), giving a total response rate of 56%, similar for both AML and ALL. Duration of response to prior therapy did not affect the response rate. All 3 patients with Philadelphia chromosome positive ALL obtained complete remission. Median remission duration was 4.7 months (range 0.6-36.6), and median overall survival was 5.0 months (0.7-40+). Median overall survival was 10.1 months in responders. Pulmonary toxicity was seen in 8 patients, of whom 2 died from adult respiratory distress syndrome. No cardiac toxicity was observed, but 3 patients had transient cerebellar toxicity. Profound myelosuppression was seen in all patients. We conclude that the sequential infusion of fludarabine and ara-C is an effective non-cardiotoxic regimen for adults with refractory, recurrent or poor prognosis acute leukemia, may be particularly useful for resistant Philadelphia chromosome positive ALL, and may warrant further investigation in this subset. Pulmonary rather than neurological toxicity may be a unique side effect of the regimen.     

2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia.

PURPOSE: The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and showed promising anti-leukemic activity in a phase I trial conducted at St Jude Children's Research Hospital. To substantiate and extend this result, we performed a phase II trial in a representative group of children and young adults with relapsed acute leukemia. PATIENTS AND METHODS: Twenty-four patients (median age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual blast cells 10 days after treatment received a second course of 2-CDA that was identical to the first. Detailed pharmacokinetic studies were performed on plasma collected from five patients. RESULTS: Eight (47%) of the 17 patients with AML had complete hematologic remissions (four after the initial course of 2-CDA), and two (12%) had partial remissions, for a total response rate of 59%. Only one child with ALL achieved remission. Seven of the responding patients underwent allogeneic or autologous bone marrow transplantation, with six remaining free of leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug-induced toxicity was hematologic, with severe neutropenia and thrombocytopenia (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses of 2-CDA. In responding patients, the median times to recovery of neutrophil counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54 nmol/L). CONCLUSION: 2-CDA given by prolonged continuous infusion has clinically significant activity against AML and merits further testing in multidrug regimens for this disease.     

Etoposide and cytosine arabinoside combination chemotherapy for refractory acute lymphocytic leukemia in childhood

Eighteen children with refractory acute lymphocytic leukemia (ALL) who had been heavily pretreated, were treated with combination etoposide and cytosine arabinoside (ara-C) chemotherapy. Seventeen of these 18 patients were in their first to third relapses; the remaining patient had never responded to induction therapy. The drug combination of etoposide followed by ara-C was administered as an intravenous (IV) infusion twice a week for two consecutive weeks, a total of four doses. The dosage was 150 mg/m2/dose for each drug. Seven (39%) of the 18 patients attained a complete remission (CR) and three (17%) attained a partial remission (PR). Complete response was obtained in two of eight patients in first marrow relapse, and in five of nine patients in second and third relapse. Five patients achieved a CR after one course of therapy and two achieved a CR after two courses of therapy. Of three patients who had previously received teniposide, two attained a CR with this combination. The duration of these responses was brief with a median of 1 month, ranging from 0.5 to 3 months, with the exception of one case, which has been in remission for 2.5 + months. Although myelosuppression was observed, none of the patients died from infection or bleeding. Allergic reaction with fever and rash was observed in two patients. The efficacy of the etoposide and ara-C combination for refractory childhood ALL is encouraging in several current reinduction regimens.     

异基因造血干细胞移植治疗血液肿瘤5例

目的；探讨基因造血干细胞移植对血液肿瘤的疗效。方法：采用异基因造血干细胞移植治疗血液肿瘤５例，包括２例第一次完全缓解（ＣＲ１）急性粒细胞白血病，１例ＣＲ１急性淋巴细胞白血病，１例急性粒细胞白血产现任昨发和１例非霍奇金氏淋巴瘤Ⅳ期ＣＲ１。其中异基因骨髓移植４例，异基因外周血造血干细胞移植１例。所有病例均采用ＴＢＩ＋ＣＹ＋ＣＣＮＵ作预处理。结果：所有病例均移植成功。２例发生急性移植抗宿主病，２例发生慢     

CAT方案治疗难治性急性髓系白血病的临床观察

目的：初步观察CAT(环磷酰胺、阿糖胞苷、拓扑替康)方案对难治性急性髓系白血病(AML)的近期临床疗效并评价此方案的不良副作用。方法：选择8例难治性AML(原发难治性AML3例，AML伴多系形态发育异常，此前有MDS病史患者3例，慢性粒细胞白血病AML变2例)．应用CAT方案治疗，其中4例治疗1疗程，其余4例治疗2疗程。结果：1例在骨髓抑制期死于感染性休克．可评价疗效7例，1例达完全缓解(CR)，3例达部分缓解(PR)，1例CML急变患者经2疗程后回到慢性期，总有效率71．4％(5/7例)，中位生存期为6．5(0．3—22^ )个月。主要不良副作用为骨髓抑制。结论：CAT方案为高危MDS、加速／急变期CML和继发于MDS的AML患者的一个有效且毒性可耐受的治疗新方案。     

Mitoxantrone and intermediate-dose cytosine arabinoside for poor-risk acute leukemias: response to treatment and factors influencing outcome.

Mitoxantrone (MIT, 12 mg/m2, i.v. 5 days) and intermediate-dose cytosine arabinoside (IDAC 1 g/m2/12 h, i.v. 3 days) was given to 43 patients with poor-risk acute leukemias (AL). Moderate or severe toxicity was infrequent. The proportion of complete remissions (CR) in the main patient categories was as follows: 15/18 (85 per cent) in acute myeloid leukemia (AML) in the first relapse, 2/6 in ALL in the first relapse, 0/2 in AML in relapse after bone marrow transplantation (BMT), 2/7 in AML refractory to first-line treatment (REF-AL), and 1/6 in postmyelodysplastic (PMD-AL) plus secondary AL (S-AL). The mortality rate during induction was 23 per cent. Median duration of CR was 24 weeks. The multivariate prognostic factor analysis on CR obtention showed that data concerning treatment for the first relapse and platelet count higher than the median of the series were favourable. On the contrary, PMD-AL, S-AL and REF-AL were unfavourable situations. A percentage of marrow erythroblasts superior to the median was a favourable prognostic factor for survival. Finally, the duration of CR after MIT-IDAC was directly related to the duration of previous CR. In conclusion, MIT-IDAC was highly effective to attain CR in AML in the first relapse. However, due to the poor long-term results in these patients, additional measures are recommended after CR.     

Fludarabine and Cytarabine as a Sequential Infusion Regimen for Treatment of Adults with Recurrent, Refractory or Poor Prognosis Acute Leukemia

We did a retrospective analysis on the safety and efficacy of sequential infusion fludarabine and cytosine arabinoside (ara-C) in treating refractory, recurrent or poor prognosis acute leukemia in adult patients. Forty-five adult patients with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) received a total of 68 courses of sequential continuous infusion of fludarabine for 2 days (total dose 71.5 mg/m²) followed by 3 days of ara-C (total dose 7590 mg/m²). Thirty-nine patients had refractory or recurrent disease, and six had other adverse prognostic features. Thirty-six patients had AML, seven had ALL, and two had CML in blastic phase. Complete remission was seen in 20 patients (44%), and partial remission in 5 patients (11%), giving a total response rate of 56%, similar for both AML and ALL. Duration of response to prior therapy did not affect the response rate. All 3 patients with Philadelphia chromosome positive ALL obtained complete remission. Median remission duration was 4.7 months (range 0.6-36.6), and median overall survival was 5.0 months (0.7-40+). Median overall survival was 10.1 months in responders. Pulmonary toxicity was seen in 8 patients, of whom 2 died from adult respiratory distress syndrome. No cardiac toxicity was observed, but 3 patients had transient cerebellar toxicity. Profound myelosuppression was seen in all patients. We conclude that the sequential infusion of fludarabine and ara-C is an effective non-cardiotoxic regimen for adults with refractory, recurrent or poor prognosis acute leukemia, may be particularly useful for resistant Philadelphia chromosome positive ALL, and may warrant further investigation in this subset. Pulmonary rather than neurological toxicity may be a unique side effect of the regimen.     

Treatment of refractory acute lymphoblastic leukemia in adults with high dose cytosine arabinoside and mitoxantrone (HAM)

In a clinical phase II study the combination of high dose cytosine arabinoside and mitoxantrone (HAM) was applied to 24 patients with refractory acute lymphoblastic leukemia (ALL). All patients had received a standardized first line treatment and were considered refractory against conventional chemotherapy as defined by nonresponse to induction treatment (n = 8), nonresponse to an alternative salvage regimen at first relapse (n = 9), second and third relapses (n = 5) and relapse after bone marrow transplantation (n = 2). Therapy consisted of HD-araC 3 g/m2 q 12 hr days 1-4 and mitoxantrone 10 mg/m2/d days 2-5 or 2-6. Twelve of the 24 patients (50%) achieved a complete remission (CR), one patient had a partial remission, and five patients were nonresponders. Five patients died in aplasia due to infections, one additional patient succumbed to HD-araC related CNS toxicity. Nonhematologic side effects consisted predominantly in infection, nausea and vomiting, mucositis and diarrhea. Recovery of blood counts occurred at a median of 28 days from the onset of treatment; the median time to CR was 33 days. Three of the 12 responders underwent subsequent bone marrow transplantations and one is alive disease free at 40+ months. The median remission duration for the remaining nine patients is 3.5 months, with one case in ongoing CCR at 36+ months; the median survival time is 5 months. Considering the selection of a highly unfavorable group of patients, these data demonstrate a significant antileukemic activity of HAM in refractory ALL and support its application as consolidation treatment during first line ALL therapy.