Treatment of acute myelogenous leukaemia in patients aged 50–65: idarubicin is more effective than zorubicin for remission induction and prolonged disease-free survival can be obtained using a unique consolidation course

From December 1987 to June 1992, 251 patients aged 50–65 with de novo acute myelogenous leukaemia (AML) were recruited to a multi-institutional randomized clinical trial. Induction therapy consisted of Ara-C (200 mg/m², continuous infusion, days 1–7) with either zorubicin (ZRB) (200 mg/m², i.v., days 1–4) or idarubicin (IDR) (8 mg/m², i.v., days 1–5). Consolidation therapy consisted of a single course of intensive chemotherapy with high-dose Ara-C (3 g/m², 3 h infusion, q 12 h, days 1–4) and m-Amsa (100 mg/m²/d, i.v., days 5–7).
The complete remission (CR) rate was (73%) with Ara-C/IDR versus (60%) with Ara-C/ZRB ( P  = 0.033). In multivariate analysis, factors found to be significant in predicting CR were normal karyotype and treatment with IDR. With a median follow-up of 73 months, the median disease-free survival (DFS) duration of all CR patients and the probability of CR at 6 years were 17 months and 29%. In multivariate analysis the only factor associated with an increased DFS duration was a normal karyotype. The median event-free survival (EFS) duration for all evaluable patients and the median overall survival duration for all eligible patients were respectively 7 and 12 months without any difference between induction arms.
The study shows that in patients aged 50–65 idarabicin is more effective than zorubicin for remission induction. However, the type of anthracycline did not influence overall survival duration. Using a unique consolidation course, we observed a prolonged DFS which compares favourably with results obtained with more prolonged consolidation therapy or maintenance treatment.     

Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia

4'-Demethoxydaunorubicin (idarubicin [IDR]) is a new anthracycline that differs from its parent compound by the deletion of a methoxy group at position 4 of the chromophore ring. This minor structural modification results in a more lipophilic compound with a unique metabolite that has a prolonged plasma half-life as well as in vitro and in vivo antileukemia activity. To determine its activity in acute myelogenous leukemia (AML), 130 consecutive adult patients between the ages of 16 and 60 with newly diagnosed disease were randomized in a single institution study to receive either IDR in combination with cytosine arabinoside (Ara-C) or standard therapy with daunorubicin (DNR) and Ara-C. The trial was analyzed using the O'Brien-Fleming multiple testing design that allowed for periodic inspection of the data at specific patient accession points. After accrual of 60 patients per arm, analysis showed that patients who received IDR/Ara-C had a superior response compared with those who received standard therapy: 48 of 60 patients (80%) achieved complete remission on the former arm compared with 35 of 60 patients on the latter (58%, P = .005). Logistic regression analysis of factors associated with complete response indicated that treatment with IDR/Ara-C offered a significant advantage to patients who presented with a high initial white blood cell count compared with treatment with DNR/Ara-C. The degree of marrow aplasia was approximately the same on each arm as was nonhematologic toxicity. Overall survival for patients on the IDR/Ara-C arm was 19.5 months compared with 13.5 months on the DNR/Ara-C arm (P = .025) at a median follow-up of 2.5 years. We conclude that IDR/Ara-C can effectively replace standard therapy with DNR/Ara-C in adult patients less than age 60 with newly diagnosed AML.     

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.     

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.     

Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia

Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.     

HA＋马利兰／HA方案初治慢性粒细胞白血病疗效观察

12例初诊的慢性粒细胞白血病(CML)接受HA+马利兰/HA方案化疗.三尖杉酯硷 2～3mg/d,阿糖胞苷100～200ng/d,7～10天为1疗程.7例在停HA后即连用马利兰4～8mg/d×5～8天.1疗程未达CR者间隔2～3周开始第2疗程直至CR.结果;1疗程CR率66.6%,有效率100%;2疗程CR率100%;达CR中位时间30天.其中2例ph_1;阳性率治疗前后对比下降平均为48.6%.提示:HA+马利兰/HA方案缓解率及有效率明显高于单一马利兰;显效快,达CR迅速,作用轻.HA+马利兰较HA能加速CML获CR.对慢性期CML细胞遗传学有较好改善.     

Mitoxantrone in combination with etoposide and cytarabine for treatment of poor prognosis acute non lymphoid leukemia patients.

BACKGROUND. The proved effectiveness and relatively low extrahematological toxicity of Mitoxantrone, Ara-C and Etoposide as single agents and in combination in the treatment of acute non lymphoid leukemia (ANLL) are well established. In a phase II study the efficacy and toxicity of an induction combination regimen with Mitoxantrone, Ara-C and Etoposide were evaluated for treatment of poor risk ANLL patients. METHODS. Twenty-seven poor prognosis ANLL patients were treated with Mitoxantrone, 7 mg/sm days 1-3; VP16, 150 mg/sm days 1-3; Ara-C, 200 mg/sm continuous infusion days 1-5. Median age of treated patients was 63 (17-78): 10 de novo leukemias (4 greater than 65 yrs 3 with cardiomyopathy); 12 secondary leukemias (5 secondary to a myelodysplastic syndrome, 5 to myeloproliferative syndrome, 2 to other neoplasias); 3 relapses; 2 refractory. RESULTS. Fifteen patients (55.5%) achieved CR (8 de novo leukemias, 3 relapses, 4 secondary leukemias); 7 died in induction, 5 progressed. Median remission duration was 27 weeks (range 5-70 wks) and overall median survival 13 weeks (range 4-80). Extraematological toxicity was low, but five patients died from infections and two from hemorrhages. CONCLUSIONS. The combination tested in this trial proved effective in the treatment of "poor risk" ANLL, but the results need to be confirmed on greater numbers of patients, mainly in the group of de novo leukemias that can't be treated with more aggressive regimens.     

Effects of low dose Ara-C regimen in acute leukemias and RAEB

Recent increase of leukemia among elderly patients prompted us to investigate the types of leukemia which can be induced into remission by low-dose Ara-C (LDAC) regimen. LDAC regimen was performed in 30 cases with overt acute leukemia (A), hypoplastic leukemia (B), and RAEB (C); Group A consists of M1 (1 case), M2 (4 cases), M3 (1 case), M4 (4 cases), M6 (1 case), and ALL (2 cases), Group B AML (8 cases), ALL (2 cases), and null (1 case), Group C RAEB (2 cases), and RAEB-T (4 cases). Complete remission (CR) rate was 23% (3/13) in group A, 64% (7/11) in group B, 0% (0/6) in group C. Partial remission rate was 33% (2/6) in group C. In group A, patients with M2 were induced into CR. In group B, both AML and ALL were induced into CR. Hypocellular marrow indicating low leukemic burden related to good sensitivity to Ara-C. Duration of CR was rather short; mean duration being 5.3 months. In group C, 2 PR cases of RAEB showed partial hematological recovery. LDAC regimen is effective especially for most of hypoplastic leukemia and some of M2. Side effects were tolerable, but all CR cases passed through bone marrow hypoplasia and needed supportive cares.     

Hexamethylene bisacetamide in myelodysplastic syndrome and acute myelogenous leukemia: a phase II clinical trial with a differentiation-inducing agent.

Hexamethylene bisacetamide (HMBA) is a potent inducer of differentiation of a number of transformed cell lines in vitro. We report results of a phase II clinical trial in 41 patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) to whom HMBA was administered by continuous infusion for 10 days and repeated after an interval of 18 to 75 days. HMBA induced a complete remission (CR) in three patients and a partial remission (PR) in six patients. The median duration of CR was 6.8 months (range 1.3 to 16 months) and 3.7 months for PR (range 1 to 7 months). No significant difference was observed between responders and nonresponders with respect to the mean HMBA plasma levels, which were 0.86 +/- 0.04 mmol/L and 0.87 +/- 0.12 mmol/L, respectively. In certain patients morphologic and chromosome analyses provided evidence that HMBA induced differentiation of transformed hematopoietic precursors. The most prominent toxicity was thrombocytopenia, generally reversible on cessation of administration of HMBA.     

Low-dose cytosine arabinoside for treating hypocellular acute leukemia in the elderly.

Ten previously untreated elderly patients with hypocellular acute leukemia received a low dose of cytosine arabinoside (Ara-C), 10 mg/m2 injected subcutaneously every 12 hours for 14-28 days. Six patients achieved a complete remission (CR) for periods ranging for 6-23 months (median 8.5 months) and the others had a partial remission (PR). Relapse has occurred in three patients to date. The median survival ranged from 10-24 months (median 14.5 months). Only two of the six patients, in whom bone marrow biopsy was performed at CR, had a normal cellularity. This change, however, did not appear to be a significant prognostic factor in those patients. In seven patients who achieved a CR or PR low-dose Ara-C was administrated as maintenance therapy at the same low dose for 10 days each month. Treatment was well tolerated in all patients despite for myelosuppression. There were no drug-related deaths. These observations suggest that low-dose Ara-C is effective in treating elderly patients with hypocellular acute leukemia.     

BAVC regimen and autologous bone marrow transplantation in patients with acute myelogenous leukemia in second remission

Twenty-one acute myelogenous leukemia (AML) patients were submitted in second remission (II CR) to BAVC conditioning regimen followed by unpurged ABMT. Transplant was done after a median of 2 months from II CR (range, 1 to 13). Median first remission (I CR) duration was 16 months (range, 1-35). Conditioning regimen was well tolerated, with no major extra-medullary toxicity. One patient died during aplasia from fungal sepsis. Of the 20 evaluable patients, nine relapsed after a median time of 6 months (range, 2 to 18). Eleven patients are in continuous complete remission (CCR) after a median follow-up of 40 months (range, 24 to 63). The duration of II CR has exceeded the duration of I CR in all patients in CCR. Projected probability of disease-free survival is 52% at 63 months.     

Randomized trial of response-oriented individualized versus fixed-schedule induction chemotherapy with idarubicin and cytarabine in adult acute myeloid leukemia: the JALSG AML95 study

A multicenter, prospective, randomized study was conducted to compare a response-oriented individualized remission induction therapy with a standard fixed-schedule induction therapy, using idarubicin (IDR) and cytarabine (Ara-C), in adult patients with acute myeloid leukemia (AML). Newly diagnosed patients with AML of age less than 65 were randomly assigned to receive either of the two schedules. Both groups received IDR (12 mg/m²) for 3 days and Ara-C (100 mg/m²) for 7 days. In the individualized group, if the bone marrow on day 8 did not become hypocellular with less than 15% blasts, patients received additional IDR for one more day and Ara-C for 2 or 3 more days. Patients achieving complete remission (CR) received the same post-remission therapy. The CR rate was 79.4% for the individualized group (n = 209) and 81.9% for the fixed group (n = 221) (p = 0.598). At a median follow-up of 81 months, 7-year predicted overall survival was 37% for the individualized group and 39% for the fixed group (p = 0.496), and 7-year predicted event-free survival was 22% for the individualized group and 23% for the fixed group (p = 0.546). Thus, the present study could not demonstrate any advantage of a response-oriented individualized induction therapy over a fixed-schedule induction therapy in this protocol setting.     

Mitoxantrone and etoposide: an effective regimen for refractory or relapsed acute myelogenous leukemia

23 adult patients with refractory or relapsed acute myelogenous leukemia (AML) received salvage chemotherapy with mitoxantrone and etoposide. The regimen consisted of mitoxantrone, 10 mg/m2/d by 30-min infusion, and etoposide 100 mg/m2/d by 30-min infusion, given 12 h apart for 5 consecutive d. Of 23 patients treated, 13 met the criteria for highly refractory disease (6 primary resistant; 4 with early relapse during maintenance; 3 relapsed and refractory to reinduction). 10 patients had relapsed off-therapy more than 6 months after achieving first CR. Overall, 14 patients (61%) achieved a complete remission (CR): 6/13 (46%) with refractory AML, and 8/10 (80%) with relapsed AML. 2 patients had a partial remission, 2 died in aplasia, and 5 were nonresponders. In responding patients, the median time for recovery of granulocyte count was 27 d. The most important nonhematologic side effect was oral mucositis, which was severe in 35% of cases. No signs of cardiac toxicity were observed. The median CR duration was 5 months (range, 2 to 12+ months). The combination of mitoxantrone and etoposide appears a highly effective and relatively well tolerated salvage regimen for refractory and relapsed AML. Its incorporation into first-line induction and consolidation programs for newly diagnosed AML patients should be considered.     

Phase II study of mitoxantrone and cytarabine in acute myeloid leukemia

Thirty-eight patients with acute myeloid leukemia (AML) were treated with mitoxantrone (Mto) combined with cytarabine (Ara-C). Five patients had received no previous treatment for acute myeloid leukemia, seven were refractory to treatment with standard first-line chemotherapy, eight had relapsed during treatment, and 18 had relapsed after treatment was stopped. Eleven of these relapses were early (within 6 months of stopping treatment). Mto was given for 5 days by iv bolus injection at a dose of 10 mg/m2 to 12 patients and at 12 mg/m2 to 26. Ara-C was given at a dose of 1 g/m2 twice daily by a 2-hour infusion for 3 days to 37 patients. One patient received Ara-C at a dose of 500 mg/m2 twice daily for 3 days. Toxicity was acceptable except for cerebellar toxicity in two patients, which was irreversible in one. Twenty-two patients (56%) achieved complete remission (CR), and four achieved partial remission (10%). Seventy-five percent of the patients who had relapsed during treatment and 58% of those who had relapsed after treatment was stopped achieved CR. Eleven patients remain in CR at a median time of 10 months (range, 3-17) after treatment. In five patients remissions have lasted greater than 1 year, one in a patient treated in second relapse and one in a patient treated in third relapse. Mto and Ara-C appear to be effective salvage therapy in acute myeloid leukemia and should be considered for incorporation into first-line induction regimens.     

Diaziquone given as a continuous infusion is an active agent for relapsed adult acute nonlymphocytic leukemia

Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of diaziquone-induced cytotoxicity for human and murine leukemia cells with increased duration of drug exposure and the relatively short terminal plasma half-life of diaziquone, 49 patients (34 acute nonlymphocytic leukemia [ANLL], six chronic myelogenous leukemia in blast crisis [CML-B], five acute lymphocytic leukemia [ALL], four 2 degrees ANLL) with leukemia were given diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL. Thrombocytopenia in these patients was felt to be a manifestation of diaziquone effect, not persistence of leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease. Diaziquone produced prolonged aplasia in patients with secondary ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed ANLL render diaziquone of interest as second-line therapy or consolidation therapy in first remission for patients with ANLL.     

Intensive chemotherapy in patients with chronic myelogenous leukaemia (CML) in accelerated or blastic phase--a report from the Swedish CML Group

In attempting to restore the chronic phase (CP) of chronic myelogenous leukaemia (CML), the Swedish CML group utilized an intensive chemotherapy protocol for 83 patients (aged 16-79 years) in accelerated (AP, n = 22) or blastic phase (BC, n = 61). Most patients received a combination of mitoxantrone (12 mg/m2/d) and etoposide (100 mg/m2/d) together with cytosine arabinoside (1 g/m2 b.i.d) for 4 d. Overall, 39 patients (47%) achieved a second CP (CP2)/partial remission (PR). Responding patients < 65 years were eligible for ablative chemotherapy followed by an allogeneic (SCT) or a double autologous stem cell transplant (ASCT). Seventeen of 34 responders < 65 years failed to proceed to transplantation as a result of early disease progression (n = 15) or disease-related complications (n = 2). The remaining 17 patients underwent SCT (n = 9; including four unrelated donor SCT) or ASCT (n = 8). Only one of the eight ASCT patients had a second ASCT; the remaining seven failed because of progression (n = 5) or hypoplasia (n = 2). The median duration of CP2/PR was 6 months (range 1-72 months). Five patients achieved a longer CP2/PR than CP1. The 1 year survival was 70% for SCT/ASCT patients (median survival 21 months), 50% for responding patients overall, but only 7% for non-responders (P < 0.001). Three SCT/ASCT patients are long-term survivors (65+, 66+ and 73+ months). In conclusion, approximately half of the patients achieved a CP2/PR after intensive chemotherapy, with a clear survival advantage for responders vs non-responders. Subsequent SCT/ASCT was feasible for half of the responders (< 65 years), and one individual underwent double ASCT. Novel therapeutic options for CML patients in AP/BP are needed.     

Phase II trial of HyperCVAD and Dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia

Dasatinib is a second generation tyrosine kinase inhibitor, with activity in imatinib resistant Ph‐positive ALL. We have treated 34 patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) (n = 19) or lymphoid blast phase of chronic myelogenous leukemia (CML‐LB) (n = 15) with the combination of dasatinib and the hyperCVAD regimen. Prior regimens included hyperCVAD plus imatinib (n = 11, 4 had transplant in first CR), other combination chemotherapy (n = 12), monotherapy with kinase inhibitors other than dasatinib (n = 9), and investigational agents (n = 2). Pretreatment ABL mutations were noted in 10 patients. The overall response rate was 91%, with 24 patients (71%) achieving complete response (CR), and 7(21%) CR with incomplete platelet recovery (CRp). Two patients died during induction and one had progressive disease. Twenty‐six patients (84%) achieved complete cytogenetic remission after one cycle of therapy. Overall, 13 patients (42%) achieved complete molecular response, and 11 patients (35%) had major molecular response (BCR‐ABL/ABL<0.1%). Nine patients proceeded to allogeneic transplantation. Grades 3 and 4 toxicities included hemorrhage, pleural and pericardial effusions and infections. The median follow‐up for patients with CML‐LB is 37.5 months (range, 7–70 months) with a 3‐year overall survival of 70%; 68% remained in CR at 3 years. For ALL patients, the median follow‐up is 52 months (range, 45–59 months) with a 3‐year survival of 26%; 30% remain in CR at 3 years. The combination of HyperCVAD regimen with dasatinib is effective in patients with relapsed Ph‐positive ALL and CML‐LB. Am. J. Hematol. 89:282–287, 2014. © 2013 Wiley Periodicals, Inc.     

Homozygous deletions of the p16 tumor-suppressor gene are associated with lymphoid transformation of chronic myeloid leukemia

The p16 gene, also referred to as MTS1, INK4, CDK4I, or CDKN2, at chromosome 9p21 has recently been described as a tumor suppressor that may be involved in a wide range of tumors. We have used a semiquantitative multiplex polymerase chain reaction assay to search for deletions of the p16 gene in 34 patients with chronic myeloid leukemia in blast crisis (CML BC), 19 patients with acute lymphoblastic leukemia (ALL), and 25 patients with acute myeloid leukemia (AML). Homozygous deletions of p16 exons were found in 5 of 10 (50%) patients with CML in lymphoid BC and in 5 (26%) ALL patients, but in only 1 (2%) case with AML. No deletions were found in CML BC of nonlymphoid phenotype. Comparison of chronic phase DNA or remission DNA with acute leukemia DNA in 5 individuals showed that the p16 deletions were acquired and not inherited, directly implicating these lesions in the pathogenesis of the disease. We conclude that functional elimination of the p16 gene, or a closely mapping gene, is involved in a significant number of patients with CML in lymphoid transformation.     

Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital

Fifty-seven adult patients with acute promyelocytic leukemia (APL) were treated between 1974 and 1984 with daunorubicin (DNR) or 4-(9- acridinylamino)methanesulfan-m-anisidide (AMSA) in combination with arabinosylcytosine (Ara-C) and 6-thioguanine (TG); they also received prophylactic heparin. Forty-one patients (72%) achieved complete remission (CR), including 11 of 12 patients who received the AMSA- containing regimen. The incidence of early fatal hemorrhage was 14%, lower than that of earlier studies or other published reports. Elevated WBC and serum lactate dehydrogenase levels at diagnosis were associated with an increased incidence of life-threatening hemorrhage and shorter remission duration. Advanced age was an unfavorable prognostic factor for male patients. Both DNR and AMSA in combination protocols are effective treatments for APL. The incidence of CR is similar to that achieved in other types of acute nonlymphoblastic leukemia (ANLL) with the same protocols, but the median duration of remission is significantly longer in APL (24 v 9 months) and the percentage of remissions longer than 60 months is also higher in APL (35% v 5%).     

Combination therapy with mitoxantrone and etoposide in refractory acute myelogenous leukemia

We have investigated the efficacy of mitoxantrone in combination with etoposide in patients with refractory acute myelogenous leukemia. The regimen consisted of 10 mg/m2/day of mitoxantrone given iv on Days 1-5; and 100 mg/m2/day of etoposide as short infusion, initially on Days 1-3 and extended to Days 4 and 5 as appropriate. Of the 26 patients treated with this combination, nine (34.6%) have achieved complete remission and two have achieved partial remission. The median duration of continuous complete remission was 85 days (range, 21-183+). Toxicity was mild and only one case of early death was observed. This combination seems to be an active regimen in refractory acute myelogenous leukemia, and its incorporation in front-line therapy seems warranted.