Clinical effects of low-dose Ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes

Forty-eight patients with acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes (MDS) were treated with low-dose Ara-C regimen (LDAC) (10 mg/m2 or 10 mg/body subcutaneously every 12 hours). Complete remission (CR) was obtained in sixteen patients (33%) and partial remission (PR) in six (16%). Seven of eight patients with hypoplastic leukemia entered CR. However, LDAC was not effective in MDS and ANLL developing from MDS. The rate of CR was 20% in relapsed or refractory ANLL. Relapse was occurred in thirteen patients until now. The median duration of remission was 7 months (range: 3-20 months). Seven of the sixteen patients who achieved CR were received LDAC at the same dose for 10 days every month as a maintenance therapy. The duration of CR of these patients was shown to be longer than that of the patients without any maintenance therapy. Myelosuppression was observed in nearly all of them and the other clinical findings including cytogenetic analysis indicated cytotoxicity rather than differentiation as the mechanism of LDAC. LDAC was effective especially in hypoplastic leukemia and the maintenance therapy was found to prolong the duration of CR.     

A multicenter,open, non-comparative,phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine,and G-CSF as induction therapy in refractory acute myeloid leukemia - a report of the Polish Adult Leukemia Group (PALG)

OBJECTIVES: To evaluate the efficacy and toxicity of cladribine (2-chlorodeoxyadenosine, 2-CdA), cytarabine (Ara-C), and granulocyte-colony stimulating factor (G-CSF) (CLAG) regimen in refractory acute myeloid leukemia (AML) in the multicenter phase II study. METHODS: The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C2 g/m2, and G-CSF. In the case of partial remission (PR), a second CLAG was administered. Patients in complete remission (CR) received two consolidation courses based on HD Ara-C, mitoxantrone or idarubicine, with or without 2-CdA. RESULTS: Fifty-eight patients from 11 centers were registered; 50 primary resistant and eight early relapsed (CR1 < 6 months). CR was achieved in 29 (50%) patients, 19 (33%) were refractory, and 10 (17%) died early. Forty of 50 primary resistant patients received daunorubicin (DNR) and Ara-C as the first-line induction therapy (DA-7), 10 received additional 2-CdA (DAC-7). The CR rates after CLAG were 58% and 10%, respectively in each group (P = 0.015). Five of six patients with myelodysplastic syndrome (MDS)/AML achieved CR. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS, 1 yr) for the 58 patients as a whole, and the 29 patients in CR were 42% and 65%, respectively. Disease-free survival (DFS, 1 yr) was 29%. Only first-line induction treatment with DA-7 significantly influenced the probability of CR after CLAG. None of the analyzed factors significantly influenced DFS and OS. CONCLUSION: CLAG regimen has significant anti-leukemic activity and an acceptable toxicity in refractory AML. The addition of 2-CdA to the first-line induction treatment may worsen the results of salvage with CLAG. The high CR rate in patients with MDS preceding AML deserves further observation.     

Autologous blood stem cell transplantation for acute myeloblastic leukemia in first complete remission. Intensification therapy before transplantation does not prolong disease-free survival

BACKGROUND AND OBJECTIVE: To compare the clinical results of two consecutive therapeutic protocols including autologous blood stem cell transplantation (ABSCT) for patients with de novo acute myeloblastic leukemia (AML) in first complete remission (CR1). DESIGN AND METHODS: Between November 1989 and January 1997, 50 patients with AML in CR1 underwent ABSCT using two consecutive protocols. In the first one (Group A, 25 patients) peripheral blood stem cells (PBSC) were collected after induction and consolidation chemotherapy courses, and ABSCT was performed immediately thereafter. In the subsequent 25 patients (Group B), PBSC were collected after consolidation alone, and a further chemotherapy course with intermediate dose cytarabine (Ara-C 1 g/m2/12 h x3 days) and mitoxantrone (12 mg/m2/d x3 days) was administered as early intensification. The conditioning regimen consisted of busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) in every case. RESULTS: Hematopoietic engraftment was slightly quicker in Group B, with median times to reach 0.5 x 10(9) neutrophils/L and 20 x 10(9) platelets/L being 13 and 12 days in Group A and 12 and 11 days in Group B, respectively. There were three graft failures (8%) (2 in Group A and 1 in Group B) and three transplant-related deaths (8%) (2 in Group A and 1 in Group B). No significant differences were observed between the groups in terms of relapse (64% at 4-years in Group A and 81% in Group B). Likewise, the actuarial 4-year disease-free survival (DFS) was not significantly different between the two groups (32% v 18%). INTERPRETATION AND CONCLUSIONS: Our study confirms that AML patients in CR1 receiving ABSCT have rapid engraftment with low mortality. However, autologous transplants with PBSC collected after consolidation chemotherapy were still associated with a high rate of relapse (RR). This RR was not apparently reduced by the administration of intermediate dose Ara-C before transplantation.     

Results of conventional-dose cytosine arabinoside and idarubicin in elderly patients with acute myeloid leukemia

Summary Conventional-dose Ara-C (200 mg/m² d 1–5) combined with idarubicin (12 mg/m² d 1–3) was employed as remission induction and consolidation therapy in 23 elderly AML patients with a median age of 66 years (range, 60–75) with AML according to the FAB criteria (M1n=3, M2n=10, M4n=6, M5n=2, M6n=2), eligible for the study. In seven patients earlier MDS had been documented by previous bone marrow aspirates. The CR rate after one induction course was 65% (15/23). Toxicity was acceptable, with four patients dying during the chemotherapy-induced hypoplasia (4/23). Although 80% of the CR patients received two additional cycles of Ara-C and idarubicin as consolidation therapy, only two patients are still in continuous complete remission more than 12 months after achieving CR. The median disease-free survival of the CR patients was 11.5 months and the median survival of the entire group was 10 months. We conclude that conventional dose Ara-C/idarubicin is an effective protocol for inducing complete remission in elderly patients with AML, but that consolidation therapy consisting of two courses of the same regimen does not produce a relevant rate of long-term disease-free survival.     

LD—HA诱导治疗非M3型老年急性髓系白血病疗效观察

目的观察小剂量高三尖杉酯碱＋阿糖胞苷（LD—HA）诱导治疗非M3型老年急性髓系白血病（AML）的疗效和不良反应。方法将35例初治老年AML患者随机分为A组（19例）及B组（16例）。A组采用LD—HA方案：高三尖杉酯碱（H）1～2mg／d,阿糖胞苷（Ara—C）25mg,q12h,第1—14天化疗。B组采用标准剂量HA或DA方案。结果1个疗程结束后,A组和B组的完全缓解（CR）率分别为68．4％和37．5％;病死率分别为10．5％和18．7％,差异有统计学意义。血液学毒性两组差异无统计学意义;非血液学毒性的发生率A组低于B组。结论LD—HA诱导治疗老年AML近期疗效好,不良反应较轻。     

DBMP-85 was effective at diagnosis and LVP was effective at relapse in a case of acute mixed leukemia

A 16 year-old boy was admitted to our hospital in April 1985, because of bilateral submandibular swellings. Hematological examination revealed Hb was 7.3 g/dl, WBC was 89,000/microliters (76% blast), and platelet was 154,000/microliters. His bone marrow was hypercellular and consisted with 91% blasts. Myeloperoxidase staining was positive for 38% of blasts. Auer rods were seen in some of blasts. Thus, the diagnosis was M1 according to FAB classification. Cytogenetic studies of 20 marrow cells were performed and all cells had 46, XY, -1, -7, 3q-, 7q-, 17q+, +2mar. Eighty five percent of blasts expressed HLA-DR and 43% of blasts expressed CD2 and CD13 simultaneously. Thus, this leukemia was considered as the hybrid type of acute mixed leukemia by surface marker analysis. DBMP-85 regimen, the chemotherapy for AML, was started after admission and complete remission (CR) was attained in June 1985. After 4 courses of post remission chemotherapy, he discharged in December 1985 and was followed at our outpatient clinic without chemotherapy. His disease was relapsed in June 1986, and the combination chemotherapy with mitoxantrone, etoposide and Ara-C was applied to him but failed to attain CR. Then, LVP protocol, the chemotherapy for ALL, was started and CR was achieved. The blasts at relapse had morphologically myeloid features, and expressed HLA-DR, CD2 and CD13 as well as at diagnosis. Cytogenetic studies at relapse showed some karyotype except gaining 12p- anomaly. Therefore, same blasts were considered to emerge at relapse. Our case suggests that LVP therapy may be effective for AML expressing myeloid and lymphoid surface markers.     

Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic leukemia in older patients

The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients (age range 60–78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m²/day, intravenously, for 3 days (23 patients), or 10 mg/m²/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m² twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1–37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/ Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.     

肿瘤坏死因子相关的凋亡诱导配体受体在白血病细胞中的表达及其意义

目的研究肿瘤坏死因子相关的凋亡诱导配体(TRAIL)受体在白血病细胞中的表达及其临床意义。方法应用RT-PCR方法对76例白血病患者的骨髓,包括15例急性淋巴细胞性白血病(急淋)、10例急性淋巴细胞性白血病缓解期(急淋缓解)、16例急性非淋巴细胞性白血病(急非淋)、11例急性非淋巴细胞性白血病缓解期(急非淋缓解)、12例慢性粒细胞性白血病急性变期(慢粒急变期)和12例慢性粒细胞性白血病慢性期(慢粒慢性期)以及25例正常人骨髓或外周血白细胞表面TRAIL受体的表达进行检测。结果急淋、急淋缓解、急非淋、急非淋缓解、慢粒急变期和慢粒慢性期患者骨髓的白细胞表面死亡受体(deadreceptor,DR)DR4和DR5表达高,而诱骗受体(decoyreceptor,DcR)DcR1和DcR2表达低,且DR4的表达高于DR5的表达;缓解期DR4和DR5的表达高于患者组;正常人骨髓或外周血白细胞中DR4和DR5表达低,而DcR1和DcR2表达高。结论TRAIL受体在不同类型的白血病细胞中的表达具有明显的差异性。     

粒细胞集落刺激因子的应用对急性白血病患者预后的影响

目的观察粒细胞集落刺激因子(GCSF)的应用对急性白血病(AL)患者预后的可能影响。方法回顾性研究171例可评价AL患者。分别采用χ2、Cox回归、KaplanMeier等方法分析1疗程完全缓解(CR)率、总CR率、治疗有效率、化疗后WBC减少时间、CR期、生存期及其影响因素;采用等级相关分析GCSF用量与CR期及生存期的关系。急性髓系白血病(AML)患者交替采用以柔红霉素 阿糖胞苷(DA)或高三尖杉酯碱 阿糖胞苷(HA)或米托蒽醌 阿糖胞苷(MA)为主的方案进行诱导缓解和缓解后治疗。急性淋巴细胞白血病(ALL)患者交替采用以长春新碱 柔红霉素 泼尼松(VDP)或长春新碱 阿霉素 泼尼松(VAP)或长春新碱 米托蒽醌 泼尼松(VMP)或环磷酰胺 长春新碱 柔红霉素 泼尼松(CODP)为主的方案进行诱导缓解和缓解后治疗。用药组均在患者WBC<1.0×109/L时予以重组人GCSF(rhGCSF)(1.5～6.0μg·kg-1·d-1),一般WBC达2.5×109/L时停用。结果(1)AL患者化疗后应用GCSF可使化疗后WBC减少时间明显缩短;但不影响患者的1疗程CR率、CR率和治疗有效率;(2)使用GCSF不影响ALL患者CR期,但明显缩短AML患者CR期;(3)使用GCSF不影响ALL患者的生存期,但缩短AML患者的生存期;(4)尚未发现使用GCSF的AML患者中因子用量多少与CR期及生存期存在相关关系。结论AML患者必须非常慎用GCSF。     

Study of differentiation of fresh human leukemic cells by low dose cytosine arabinoside (LD Ara-C) and 12-O-tetradecanoylphorbol-13-acetate (TPA)

The effect of LD Ara-C (10(-8) mol/l) (Ara-C), TPA (1.6 x 10(-7) mol/l) and 13-cis-retinoic acid (RA) (10(-6) mol/l) on the differentiation in liquid culture of bone marrow cells from 5 patients with acute lymphoblastic, 17 patients with acute myelogenous leukemia, 1 patient in myeloid and 1 in lymphoid crisis of chronic granulocytic leukemia was studied. Ara-C induced morphological and cytochemical differentiation into monocytic cells in 2 cases (M1, M5 type). TPA induced convincing morphological and cytochemical features of maturation into monocytic cells in 4 cases (two M1, one M2, and one M5 type) and into differentiated myeloid cells in 2 cases (M1, M4 type). RA in one case (M2 type) out of three AML studied induced cytochemical and immunocytochemical features of maturation. The results of the study indicate that although TPA is a better inducer of blast cell differentiation than Ara-C, however, neither is a potent differentiation agent of leukemic blasts in liquid culture. The heterogeneity of leukemic blasts within the same type of leukemia was confirmed by their different response to differentiating agents.     

FLAG方案再诱导化疗急性髓细胞白血病临床观察

目的:初步探讨氟达拉滨(FDR)、高剂量阿糖胞苷(Ara-C)和粒细胞集落刺激因子(G-CSF)即FLAG方案在急性髓细胞白血病(AML)再诱导化疗中的疗效及不良反应。方法:12例经标准HA、DA、MA或IA方案化疗1疗程后未达完全缓解(CR)、骨髓原始细胞下降低于60%的AML患者,予FLAG方案再诱导化疗,即FDR30mg.m-2.d-1静脉滴注,d1～5;Ara-C1g/m2,静脉滴注,每12h1次,d1～5;G-CSF300μg/d皮下注射,第0天开始至白细胞恢复正常。结果:9例(75%)患者获得CR,3例(25%)患者获得部分缓解(PR)。主要不良反应为骨髓抑制,非血液学不良反应不明显。结论:FLAG方案再诱导化疗AML耐受性较好,有效率较高,不良反应可耐受。     

FLAG-IDA方案可改善高危急性髓细胞性白血病患者初始诱导缓解治疗的疗效

目的: 分析高危急性髓细胞性白血病（AML）患者采用FLAG-IDA方案 [甲氧柔红霉素（IDA）联合氟达拉滨（Flu）、阿糖胞苷（Ara-C）和粒细胞集落刺激因子（G-CSF）]进行初始诱导缓解治疗的临床疗效及预后。方法：将2010年1月至2017年1月廊坊市中医医院急诊科诊治的80例AML患者纳入研究，采用随机数字表法将患者分为FLAG-IDA组（41例）和对照组（39例），FLAG-IDA组予甲氧柔红霉素、氟达拉滨、阿糖胞苷及粒细胞集落刺激因子进行初始诱导缓解治疗，对照组予甲氧柔红霉素联合阿糖胞苷组成的IA/DA（3+7）方案进行初始诱导缓解治疗，记录患者治疗过程中出现的不良反应，比较2组患者在第一次诱导治疗结束后的临床疗效，并在患者第一次初始诱导缓解治疗结束后对患者进行为期24个月的随访，记录患者疾病复发或进展情况，比较2组临床疗效及预后。结果：FLAG-IDA组第一次诱导治疗后的完全缓解率、总有效率、总生存率及无病生存率明显高于对照组，未缓解率明显低于对照组（P均＜0.05）；2组部分缓解率及总不良反应发生率比较，差异无明显统计学意义（P均＞0.05）。结论：FLAG-IDA方案用于高危AML患者初始诱导缓解治疗具有较好的临床疗效，且近期总生存率及无病生存率较高，无严重不良反应。     

低增生骨髓增生异常综合征的由来和转归

目的探讨低增生骨髓增生异常综合征（ＭＤＳ）的由来和发展。方法对我院１０年中确诊的２５例低增生ＭＤＳ进行了系统分析,对其中１７例患者进行长期追访。结果（１）低增生ＭＤＳ占同期确诊为ＭＤＳ的２１９例患者中１１．４％,确诊时平均年龄为（４４．８±１４．７）岁。（２）ＦＡＢ分型：难治性贫血（ＲＡ）１１例,难治性贫血伴原始细胞增多（ＲＡＥＢ）１４例。（３）低增生ＭＤＳ很可能是ＭＤＳ患者病程中一个阶段,其骨髓增生活跃和低下可以相互转化,这种转化不但可以发生在同一ＦＡＢ亚型内,也可以发生在不同亚型相互转化时。（４）长期随访的１７例患者中有７例转为急性白血病,占４１．２％,６例为急性粒细胞白血病,１例为急性淋巴细胞白血病;７例中３例转为低增生白血病,４例为增生活跃或极度活跃白血病。（５）１７例患者中７例自低增生ＲＡＥＢ转为急性白血病时间为１～７４个月,中数为２７个月。（６）低增生ＭＤＳ的产生与治疗药物无明显相关。结论低增生ＭＤＳ很可能为ＭＤＳ病程中一个阶段而非一种特殊类型。     

Detection of cytarabine resistance in patients with acute myelogenous leukemia using flow cytometry

Cytarabine (Ara-C) is currently used in the treatment of adult acute myeloid leukemia (AML). To predict the results of induction chemotherapy, it could be useful to detect leukemic cells that are resistant to Ara-C in patients with AML. Using a bromodeoxyuridine/DNA (BrdUrd/DNA) staining method in flow cytometry (FCM), we have developed a cell resistance index to Ara-C (RI). The technique has been applied to 121 bone marrow (BM) samples from patients with de novo AML treated by a regimen containing Ara-C and daunorubicin (DNR). Ninety-seven patients achieved a complete remission (CR), and 24 patients did not and were considered drug-resistant (DR). The BM cells collected at diagnosis were cultured for 48 hours and underwent BrdUrd/DNA analysis. Among 25 patients with no or very low proliferative activity (<3% of cells in S-phase), the proportion of DR patients (nine of 25) was significantly higher than in a second group of 96 patients with detectable proliferative activity (15 of 96) (P < .025). Within this second group, there was a first group of nine patients with high RI values, which included only DR patients; a second group of 63 patients with low RI values, which included 62 CR patients; and a third group of 24 patients with intermediate RI values, which included 19 CR and five DR patients. In view of this series, our results show that it is possible to detect a majority of DR patients treated by Ara-C.     

应用大剂量强化治疗延长急性白血病患者缓解期和生存期

采用大剂量阿糖胞苷及柔红霉素(HD-AD)治疗缓解急性髓系白血病(AML)22例,大剂量氨甲喋呤及左旋门冬酰胺酶(HD-MA)治疗缓解期急性淋巴细胞白血病(ALL)8例。使AML和ALL的平均缓解期分别达到26.6月和32.5月,明显优于一般巩固化疗效果(分别为11.6月和7.0月),2年以上的生存率达57%,3年以上者27%,表明大剂量化疗用于急性白血病的巩固治疗是延长缓解期和生存期的有效措施之一。     

Daunorubicin,cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety,tolerance and early outcome—Polish Adult Leukemia Group (PALG) pilot study

In 1992–1993, synergistic interaction of ribonucleotide reductase inhibitors (fludarabine, cladribine) and cytarabine (Ara-C) increasing Ara-CTP concentration in myeloblasts was proved. Based on these findings and encouraging results of the addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early outcome. The DAF regimen consisted of daunorubicine 60 mg m⁻² day⁻¹ iv on days 1–3 and fludarabine 25 mg m⁻² day⁻¹ iv on days 1–5 given before cytarabine 200 mg m⁻² day⁻¹ in ci on days 1–7. Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study between September 2003 and August 2004. Achieved response rate in the whole study population was 56%; n = 16 patients with complete remission (CR), and n = 3 patients with partial remission (PR). Fifteen of 16 patients achieved CR after the first course of therapy. Only 9% of total population died before the assessment of remission. All patients developed severe neutropenia. Serious infections were observed in 47% of the cases. Severe thrombocytopenia was observed in 72% of the patients. All patients required substitution of platelet concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis, vomiting were of low frequency. Liver, kidney, or circulatory failure, diarrhea, or polyneuropathy were not observed. The probability of overall survival (OS) for 1 year for the whole study population (34 patients) and the group of 16 patients in CR was: 44% (95% confidence interval [CI] 36–52%) and 69% (95% CI 55–83%), respectively. The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI 22–54%). Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable toxicity and early efficacy.     

Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: A phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group

 Twenty-one patients with acute myeloid leukemia (AML) who failed to enter complete remission (CR) after first-line standard-dose remission-induction therapy with 7 days of cytarabine and 3 days of daunorubicin were treated with a salvage regimen containing intermediate-dose cytosine arabinoside (Ara-C) 2×500 mg/m²/day during 7 days in combination with continuous infusions of idarubicin 12 mg/m²/day on days 1, 3, and 5. Twenty patients were considered primary resistant, and one patient had a partial remission after two remission-induction courses. Overall, 11 patients (52%, 95% confidence interval: 30–74%) entered CR. Three patients died during hypoplasia and seven patients had resistant disease or a partial remission. The remission rate in this study compares favorably with the results obtained in similar patient categories. The toxicity of this salvage regimen was remarkably mild. No extramedullary toxicity was observed except for hepatic dysfunction in seven patients. The median duration of remission was 8.5 months, and ultimately, all complete remitters have relapsed except the patient who died from infectious complications after allogeneic bone marrow transplantation (BMT). This study shows that new intensive chemotherapy regimens may be effective after failure of primary treatment. Salvage regimens containing intermediate/high-dose Ara-C and/or alternative anthracyclines or anthracenes should be induced in the treatment of young patients with de novo AML. Received: 12 September 1995 / Accepted: 24 November 1995     

Efficacy of fludarabine, intermittent sequential high-dose cytosine arabinoside, and mitoxantrone (FIS-HAM) salvage therapy in highly resistant acute leukemias

Patients with refractory acute leukemias after intensive induction and salvage attempts have a particularly poor prognosis and therapeutic options are limited. In the current study, the pharmacologically based FIS-HAM regimen was applied, which included fludarabine 15 mg/m2 q 12 h (days 1, 2, 8, and 9), cytosine arabinoside as a 45-min infusion every 3 h at 750 mg/m2 per single application (days 1, 2, 8, and 9), and mitoxantrone 10 mg/m2 (days 3, 4, 10, 11). Twenty-six intensively pretreated patients [median age: 38 years; range: 22-65; 16 cases of acute myeloid leukemia (AML) and 10 of acute lymphoblastic leukemia (ALL)] were included. Of 16 patients with AML, 5 achieved a complete remission (CR, 31%), 1 a partial remission (PR, 6%), 2 were nonresponders (13%), and 8 succumbed to early death (ED, 50%). Of 10 patients with ALL, 5 achieved a CR, 1 a PR, 1 was a nonresponder, and 3 died early. Overall, the CR rate was 38%. The median disease-free survival time was 50 days and median survival 90 days. Two patients underwent allogeneic bone marrow transplantation and are alive after 27 and 28 months. Neutropenia amounted to a median of 46 days. Toxicity WHO III/IV included infection (61%), diarrhea (48%), nausea/vomiting (43%), impairment of heart function (30%), and mucositis (26%). The current data indicate a significant activity of FIS-HAM chemotherapy in advanced acute leukemias. However, due to its pronounced toxicity, this regimen should be restricted to third-line therapy for patients expecting a suitable donor for allogeneic transplantation, and supportive treatment should be optimized.     

A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an alternative treatment to patients with high-risk acute leukemia lacking a human leukocyte antigen-matched donor. We analyzed 173 adults with acute myeloid leukemia (AML) and 93 with acute lymphoblastic leukemia (ALL) who received a haplo-HSCT in Europe. All grafts were T cell-depleted peripheral blood progenitor cells from a direct family or other related donor. At transplantation, there were 25 patients with AML in CR1 (complete remission 1), 61 in more than or equal to CR2, and 87 in nonremission, and 24 with ALL in CR1, 37 in more than or equal to CR2, and 32 in nonremission. Median follow-up was 47 months in AML and 29 months in the ALL groups. Engraftment was observed in 91% of the patients. Leukemia-free survival at 2 years was 48% plus or minus 10%, 21% plus or minus 5%, and 1% for patients with AML undergoing transplantation in CR1, more than or equal to CR2, and nonremission, and 13% plus or minus 7%, 30% plus or minus 8%, and 7% plus or minus 5% in ALL patients, respectively. In conclusion, haplo-HSCT can be an alternative option for the treatment of high-risk acute leukemia patients in remission, lacking a human leukocyte antigen-matched donor.     

T-Cell Acute Lymphoblastic Leukemia as a Secondary Leukemia after a 3-Year Remission of Acute Myelocytic Leukemia

Therapy-related myelodysplastic syndrome and therapy-related acute myelocytic leukemia (AML) are now recognized as hematologic malignancies that occur a few years after chemotherapy for primary malignancy with alkylating agents or topoisomerase II inhibitors. The secondary leukemia is usually AML and sometimes is preceded by a myelodysplastic syndrome. Acute lymphoblastic leukemia (ALL) as a secondary leukemia is quite rare, and secondary T-cell ALL after AML is even rarer. We report a case of a 56-year-old woman who developed T-cell ALL after a 3-year remission of AML (M2). We thought that this case would be extremely valuable for studying the etiology and biological characteristics of T-cell ALL as a secondary leukemia after AML.