A complete remission can be achieved despite persistence of abnormal bone marrow promyelocytes in acute promyelocytic leukemia--experience in 2 patients.

Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) and is distinguished from other subsets of AML by its distinctive morphology, specific chromosomal abnormality, associated consumptive coagulopathy, and response to treatment. Interestingly, patients with APL frequently enter complete remission without undergoing a characteristic period of bone marrow hypoplasia. In two cases in this report, complete remission was achieved without bone marrow hypoplasia without further additional course of chemotherapy despite the appearance of persistent malignant cells in the bone marrow after first induction chemotherapy. During the period of treatment, severe coagulopathy occurred in both cases but resolved as the patients entered into remission. Remission in patients with APL may occur even when induction therapy fails to cause marrow hypoplasia or to eradicate replicative cells. To avoid unnecessary exposure to toxic therapy, caution should be exercised in assessing the adequacy of remission induction treatment.     

去甲柔红霉素联合中剂量阿糖胞苷强化治疗急性髓细胞白血病（附53例报告）

目的探讨去甲柔红霉素联合中剂量阿糖胞苷(IDAra-C)治疗急性髓细胞白血病(AML)治疗效果。方法用去甲柔红霉素联合IDAra-C,对53例AML患者进行化疗,其中用于原发性治疗30例,用于难治性复发性AML诱导缓解治疗23例。结果原发性治疗组中,中位完全缓解期17个月,治疗相关死亡2例;难治性复发性AML组12例取得完全缓解。结论去甲柔红霉素联合IDAra-C,用于原发性AML的缓解治疗,可减少复发率,延长缓解期,提高无病生存率,用于难治性复发性AML的治疗也疗效明显,绝大多数病人可耐受治疗。     

Mitoxantrone and cytosine arabinoside in previously untreated adult patients with acute non-lymphocytic leukemia

Twenty-five adult patients with previously untreated acute non-lymphocytic leukemia (ANLL) were treated with mitoxantrone (Mto) 12 mg/m2 daily by 30 minutes intravenous (IV) infusion for 3 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 7 days, as an induction therapy. After complete remission (CR) was observed, they were given two more courses of consolidation therapy which was as Mto 12 mg/m2 daily by 30 minutes IV infusion for one day, and Ara-C 200 mg/m2 daily by 30 minutes IV infusion for 5 days. CR was obtained in 18 of 25 patients (72%). Median remission duration was 294 days and length of survival was 366 days. 11 patients (44%) are still in remission. Myelosupression developed in all patients following induction therapy, but it was not observed after consolidation therapies. Non-hematological side-effects consisted of nausea, vomiting, alopecia, stomatitis, and transient elevation in liver enzymes. Our therapeutic responses are similar to those obtained by others.     

Secondary myelodysplastic syndrome after treatment for promyelocytic leukemia: clinical and genetic features of two cases

Acute promyelocytic leukemia (APL) represents a biologic and clinically well-defined subtype of acute nonlymphocytic leukemia with specific morphologic and karyotypic characteristics. Although secondary leukemia and myelodysplastic syndromes (MDS) are the most frequent secondary neoplasms following chemotherapy for acute leukemia, their development after complete remission in patients with APL is uncommon. We describe the clinical and genetic features of two APL patients who achieved CR after chemotherapy and all-trans retinoid acid treatment and subsequently developed a MDS. Therapy-related MDS karyotype changes such as abnormalities of chromosomes 5 and 7 were found in the cytogenetic analysis. Since TP53 alteration was detected in one case, possible implications of these findings in the onset of MDS are discussed.     

Phase II study of cyclophosphamide, doxorubicin, and vincristine (CAV) and etoposide plus cisplatin (EP) alternating chemotherapy combined with radiotherapy in small cell lung cancer

The development of drug resistance is the major limiting factor influencing the survival of patients with small cell lung cancer (SCLC). We have thus examined the activity of cyclophosphamide, doxorubicin and vincristine (CAV) alternating with etoposide and cisplatin (EP) in 35 patients with SCLC. The treatment courses were alternated every 3 or 4 weeks. After induction chemotherapy, patients with limited disease (LD) received thoracic radiotherapy (5000 cGy), prophylactic cranial irradiation (3000 cGy) and maintenance chemotherapy and patients with extensive disease (ED) received maintenance chemotherapy only. In this group of 35 patients, 13 had limited disease (LD) and 22 had extensive disease (ED). After completion of the therapy, 100% of the patients with LD achieved complete plus partial remission (CR + PR) and 68% of the patients with ED achieved CR + PR. The median survival time was 66 weeks (15.3 months) in patients with LD and 44 weeks (10.2 months) in patients with ED. The over all survival for patients with LD was superior to that for patients with ED (p less than 0.05). Also, median response duration for patients with LD (35 wks) was longer than that for patients with ED (17 weeks) (p less than 0.05). The primary site was the most vulnerable site to relapse (18 patients). Toxicity was mild to moderate and acceptable, and there were no treatment-related deaths. These results suggest that the alternation of CAV and EP is effective treatment strategy in the management of SCLC. A randomized controlled study will be required to discriminate the actual effect of this alternating regimen.     

Sequentielle Induktionschemotherapie und Strahlenbehandlung inoperabler kleinzelliger Bronchialkarzinome

Summary To study the potential benefit of sequential chemotherapy in inoperable small cell lung cancer (SCLC), from 1982 to 1986 ninety-one patients with histologically proven and previously untreated SCLC (median age: 53 years; median Karnofsky status: 80%) were randomly assigned to an initial therapy with adriamycin (since 1984 epirubicin), cyclophosphamide, vincristine (ACO resp. EPICO) or etoposide/cisplatin (VP16/DDP). Treatment courses were repeated every 3 weeks for a total of 6 courses with a crossover after a maximum of 3 cycles of either regimen. Limited disease (LD) patients with bronchoscopical, computertomographical and (re-) mediastinoscopical complete remission (CR) randomly received either a thoracic irradiation with 40 Gy or observation only. Overall, 60 out of 85 evaluable patients achieved an objective remission. A CR was observed in 24/51 patients (47%) with limited disease, and in 8/34 patients (24%) with extensive disease. Both, ACO (EPICO) and VP16/DDP were equally effective as initial and second-line therapy. Moreover, after failure to the initial therapy an objective remission could be achieved in 13% of the patients following the alternative second line combination. In 28% of LD patients with an otherwise complete remission residual tumor was detected by (re-) mediastinoscopy. Median survival times were 14 (CR: 16) months in LD patients and 10 (CR: 15) months in ED patients. At present, median survival is significantly improved in irradiated versus non-irradiated LD patients (25 vs. 13 months, p<0.04). The remission rates and median survival times observed in this study are comparable to those of a historical control group treated with ACO plus radiotherapy alone.

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Abkürzungsverzeichnis LD limited disease - ED extensive disease - ACO Adriamycin, Cyclophosphamid, Vincristin - EPICO Epirubicin, Cyclophosphamid, Vincristin - VP/DDP etoposide, cisplatin - CR complete remission - PR partial remission - NC no change - PD progressive disease Die vorliegende Arbeit enthält wesentliche Teile der Dissertation von Herrn W. Eberhardt.Die Untersuchungen wurden mit Mitteln des Bundesministers für Forschung und Technologie gefördert (038457).     

急性早幼粒细胞白血病患者止血和凝血分子标志物的检测分析

目的:检测急性早幼粒细胞白血病(APL)患者止血和凝血分子标志物含量变化及其临床意义。方法:采用ELISA方法检测46例APL患者于化疗前和完全缓解后的血浆血小板α颗粒膜糖蛋白-140(GMP-140)、D-二聚体(D-D)、凝血酶-抗凝血酶复合物(TAT)、凝血酶原片段F1+2、纤溶酶-抗纤溶酶复合物(PAP)含量,并与38例正常人对照。结果:化疗前46例APL患者血浆TAT、D-D、F1+2、GMP-140、PAP含量明显高于正常对照组(P<0.05~0.01),完全缓解后GMP-140、TAT、D-D、F1+2、PAP水平恢复正常;未缓解和复发患者GMP-140、TAT、D-D、F1+2、PAP水平与初诊患者无明显差异(P>0.05)。结论:APL患者凝血系统激活、纤溶亢进,但随病情好转可逐渐改善。止血和凝血分子标志物检测有助于APL病情和疗效观察。     

Refractory and relapsing Hodgkin's disease: Role of high-dose chemotherapy with bone marrow transplantation

Summary Thirty percent of adult patients with Hodgkin's disease fail primary treatment or relapse after treatment. Whereas overall mortality for Hodgkin's disease is about 20%, half the patients who relapse will die.Among patients with refractory or relapsing disease, about a third can be rescued by conventional salvage treatment. Unfortunately, except for patients with late relapse, remission after conventional salvage treatment is generally not of long duration.However, durable complete remissions can now be achieved in nearly a third of patients with refractory or relapsing disease by means of very aggressive (myeloablative) chemotherapy with consecutive autologous bone marrow transplantation (aBMT).The rate of durable complete remissions seems to be even higher if previous exposure to chemotherapeutic agents is not in excess of two different treatment protocols (optimal timing of aBMT) and if responsiveness to cytotoxic drugs is preserved (low degree of drug resistance).Bone marrow transplantation should be restricted to patients whose resulting long-term prognosis justifies such radical treatment. Reflecting ongoing clinical therapy-studies, in particular in Germany, the role of bone marrow transplantation in a general concept of salvage treatment should be pointed out. Patients should be considered candidates if they fail alternating primary chemotherapy or develop an early relapse after this treatment, but still show responsiveness to chemotherapeutic agents.List of Abbreviations aBMT autologous bone marrow transplantation - pS pathological staging - C[M]OPP/ABVD Cyclophosphamide [Mustargen], Vincristine (Oncovin), Procarbazine, Prednisone/Doxorubicin (Adriamycin), Bleomycin, Vinblastine, Dacarbazine - CEVD Lomustine (CCNU), Etoposide, Vindesine, Dexamethasone - Dexa-BEAM Dexamethasone, Carmustine (BCNU), Etoposide, Cytarabin (Ara-C), Melphalan - COPP/ABV/IMEP Cyclophosphamide, Vincristine (Oncovin), Procarbazine, Prednisone/Doxorubicin, Bleomycin, Vindesine/Ifosfamide, Methotrexate, Etoposide, Prednisone - CEP Lomustine (CCNU), Etoposide, Prednimustine - MIME Mitoguazone, Ifosfamide, Methotrexate, Etoposide - CVB Cyclophosphamide, Etoposide (Vepeside), Carmustine (BCNU) - CR complete remission - n.r. not reported     

Spotlight on Gemtuzumab Ozogamicin in Acute Myeloid Leukaemia

Gemtuzumab ozogamicin (Mylotarg) is a conjugate of a monoclonal antibody and calicheamicin, which targets the membrane antigen CD33 in CD33-positive acute myeloid leukaemia (AML) and, after cell internalization, releases a derivative of the cytotoxic calicheamicin component. In the US, it is approved as monotherapy in patients aged>or=60 years with a first relapse of AML who are ineligible for other cytotoxic therapy.Monotherapy with gemtuzumab ozogamicin results in complete remission (CR) or CR with incomplete platelet recovery (CRp) in approximate, equals 25% of adults (including those aged>or=60 years) with CD33-positive AML in first relapse. Preliminary data indicate a potential role for gemtuzumab ozogamicin as a component of induction or consolidation regimens in adults and, based on an early study, in the treatment of children with AML, although randomized, controlled studies are needed. Serious adverse events, notably hepatotoxicity, characterize its tolerability profile, but gemtuzumab ozogamicin is comparatively well tolerated by most patients. Gemtuzumab ozogamicin is a valuable new treatment option for patients aged>or=60 years with CD33-positive AML in first relapse for whom other cytotoxic chemotherapy is not considered appropriate; patients with a first CR (CR1) of >12 months are likely to have the best outcome.     

Adult T Cell Leukaemia

Adult T cell leukaemia (ATL) is an aggressive clonal malignancy of mature activated T cells, caused by the human T cell lymphotropic virus type I (HTLV-I) infection. ATL continues to have a very bad prognosis because of the intrinsic resistance of leukaemic cells to conventional or even high-dose chemotherapy and because of the associated severe immunosuppression. Even though conventional chemotherapy remains the standard treatment in acute and lymphomatous types of the disease, the benefit of this intensive approach is not well established in chronic and smouldering ATL. Combination chemotherapy regimens, in particular those designed for the treatment of aggressive non-Hodgkin's lymphomas or acute lymphoblastic leukaemia, have little effect in the treatment of ATL. Different combination regimens of conventional chemotherapy have been investigated in Japan, and recent results of intensive induction therapy showed a complete remission (CR) rate of about 40% in the aggressive forms of the disease. However, most of the patients relapsed and eventually died. Allogeneic bone marrow transplantation has been used in the treatment of a very small number of patients with ATL. High toxicity and transplant-related mortality were observed in these immunocompromised patients. New cytotoxic agents have also been used in pilot phase II studies in refractory or relapsed ATL patients, but significant results have only been observed with deoxycoformycin. Recently, promising results have been obtained with anti-Tac monoclonal antibodies directed against the alpha-chain of the interleukin-2 receptor (CD25), which is highly expressed on ATL cells but not on normal resting lymphocytes. Promising results were also reported in 2 phase II studies with combination therapy comprising the antiretroviral agent zidovudine and interferon-alpha (IFNalpha). In previously untreated patients with acute ATL, high and rapid (usually within 2 weeks) response rates were reported. In contrast, in lymphomatous ATL, both studies suggested a milder and slower effect of zidovudine and IFNalpha. In this case, this combination may be used as maintenance therapy after a CR or good partial response induced by polychemotherapy. Since cross resistance between chemotherapy and zidovudine and IFNalpha does not seem to occur, a combination with best induction polychemotherapy is warranted.     

Recent progress in the treatment of adult acute leukemia

In 3 studies for adult acute myelogenous leukemia (AML) treated with BHAC-DMP, BHAC-DMP(II) and M-85 from 1979 to 1987, intensive induction resulted in a higher cure rate, since reduction of the blasts in bone marrow at 2 weeks after the initiation of therapy to less than 20% was the most significant prognostic factor to predict the long complete remission (CR), followed by initial WBC counts (less than 60,000/cmm) and achievement of CR within 50 days or by one course of induction therapy. However, it seemed impractical to give very intensive chemotherapy during the induction because of the high frequency of complications due to prolonged myelosuppression. Consolidation should be as intensive as possible. Non-cross resistant drugs will theoretically produce better results. In M-85 protocol, 71% of 41 adult AML achieved CR. The predicted 3.5-year survival and CR length of CR cases are 74 and 56%; respectively. The preliminary results of JALSG-AML87 and -ALL87 were also reviewed.     

Kidney transplantation in a patient with end stage renal disease after complete remission of acute promyelocytic leukemia

In general, a 2-yr disease-free duration is recommended before kidney transplantation (KT) in end-stage renal disease (ESRD) patients who also have acute leukemia. However, the optimal disease-free interval has not been specified for all subtypes of acute leukemia. Among these subtypes, acute promyelocytic leukemia (APL) shows a favorable prognosis and low relapse rate compared to other types of leukemia. We here report KT after complete remission (CR) of APL in an ESRD patient. Irreversible kidney injury developed in a 23-yr-old man with APL. First, we induced CR and subsequently performed KT 7 months after the achievement of CR. The patient's clinical course after KT was favorable, without allograft rejection or relapse of APL up to 1 yr after KT. On the basis of our clinical experience, it is suggested that a long wait may not be necessary before KT in patients with ESRD and APL.     

Fetal liver infusion in acute myelogenous leukaemia

Forty-five patients with acute myelogenous leukaemia (AML) received induction chemotherapy with either a conventional dose of cytarabine and daunorubicin (27 patients) or a low dose of cytarabine (18 patients). Maintenance chemotherapy was given to all responders. In 14 of 39 evaluable patients, infusion of fetal liver cells from 10-24 weeks old foetuses was given following induction as well as maintenance therapy. Six of 14 patients (43%) achieved a complete remission; 2 showed evidence of transient engraftment documented by analysis of sex chromosomes and RBC antigens (1 patient each). Fetal liver infusion within 6 days of completing induction chemotherapy appeared more effective than when given later. Five of 25 patients (20%) who did not receive fetal liver infusion achieved a complete remission. The present work suggests that fetal liver infusion given following induction chemotherapy may increase the remission rate in AML either by temporary engraftment or by accelerating the rate of haematological recovery.     

Intensive short-term chemotherapy in patients with advanced breast cancer

Summary Aiming at a high complete remission rate with an intensive induction regimen, 27 patients with advanced breast cancer were given three cycles of VAC chemotherapy consisting of vinde-sine 3 mg/m² i.v. on days 1 and 12, adriamycin 40 mg/m² i.v. on days 1 and 12, and cyclophosphamide 200 mg/m² p.o. on days 3–6 and 14–17 together with medroxyprogesterone acetate (MPA) 1,500 mg p.o. daily during the induction phase and 1,000 mg p.o. thereafter until relapse. These VAC double cycles were repeated twice with 3-weekly intervals for a total induction period of 15 weeks. In responders, including no change, the chemotherapy was discontinued thereafter, and the patients were observed until relapse with a maintenance therapy of MPA 1,000 mg p.o. daily.A complete remission (CR) was achieved in 8 (29.6%) and a partial remission (PR) in 13 (48.2%) of the 27 patients (CR + PR 77.8%). A no change (NC) status was found in 6 patients (22.2%). There were no nonresponders. The median duration of the CR was 20 (5–42) months with two patients still in CR at 33 and 36 months, of the PR 8.3 (4–13.5) months, and of the NC 6.7 (2–13) months. The treatment was tolerated without life-threatening toxicity or interval prolongation by all patients. No dose-limiting cardiac toxicity was observed in these patients regularly controlled by left ventricular ejection fraction (LVEF). The high response rate of this intensive induction regimen warrants further investigation. Complete remission was achieved only in patients without previous chemotherapy, with marked tumor regression after the first chemotherapy cycle and when there was no extensive bone involvement.Abbreviations ADR Adriamycin - CK Creatinine kinase - CK-MB Cardiac muscle specific isoenzymes - CMF Cyclophosphamide, methotrexate, 5-FU - CNS Central nervous system - CR Complete remission - CYC Cyclophosphamide - DFI Disease-free interval - ECG Electrocardiogram - LMF Chlorambucil, methotrexate, 5-FU - LVEF Left ventricular ejection fraction - MPA Medroxyprogesterone acetate - NC No change - PD Progressive disease - PR Partial remission - VAC Vincristine, adriamycin, cyclophosphamide - VEC Vincristine, epirubicin, cyclophosphamide - VDS Vindesine - WBC White blood cell count     

Trisomy 21 and other chromosomal abnormalities in acute promyelocytic leukemia

We describe a case of acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) and trisomy 21 as an additional change in a patient who died at relapse after achieving complete remission (CR) for the duration of 20 months. A survey of 42 cases of APL with cytogenetic study performed at our institution over the past 10 years showed 12 cases (28.6%) having chromosomal changes in addition to t(15;17). Trisomy 8 and trisomy 21 as additional changes were noted in 4 and 2 cases, respectively, with one patient showing both trisomies simultaneously. Two cases showed t(15;17) in hyperdiploid clones. Among the 10 patients with follow-up data, all eventually relapsed and none achieved continuous complete remission 1. Survival analysis performed in APL patients with adequate follow-up data showed no significant difference in overall and disease free survival between those with and without additional cytogenetic changes. After excluding cases with one induction death, the overall survival was significantly in favor of the group without additional cytogenetic abnormalities (P = 0.022). Late relapses may therefore be significantly more common in APL patients with additional cytogenetic abnormalities, and may not be reflected by analysis focused at three-year survival only. As APL is now considered a curable disease, any confirmed long-term survival impact of additional cytogenetic changes is expected to have important management implications.     

Complete Remission Status before Autologous Stem Cell Transplantation Is an Important Prognostic Factor in Patients with Multiple Myeloma Undergoing Upfront Single Autologous Transplantation

Upfront high-dose myeloablative chemotherapy followed by a single autologous stem cell transplantation (ASCT) is the standard therapy for patients under the age of 65 years with newly diagnosed multiple myeloma (MM). Because disease status after induction chemotherapy is variable, we evaluated the prognostic effect of disease status before ASCT, especially in patients who were initially chemosensitive. We retrospectively analyzed the initially chemosensitive MM patients (≥ partial remission [PR]) enrolled in the Korean Multiple Myeloma Working Party Web-based registration system (www.myeloma.or.kr). Between November 1996 and January 2007, 197 MM patients (median age 53 years) were treated with induction chemotherapy followed by a single ASCT. All patients received peripheral blood stem cell (PBSC) support after conditioning with melphalan (Mel) alone. We considered those patients with no detectable M-protein regardless of the result of immunofixation to be in complete remission (CR) in this study. The median follow-up times were 29.2 months (range, 5.4 to 103.8 months) from the day of diagnosis and 22.4 months (range, 0.4 to 96.0 months) from the day of ASCT. Before ASCT, 63 patients (32%) were in CR and 134 (68%) were in partial remission (PR). The patients in CR had significantly longer overall survival (OS) from the day of ASCT compared with those in PR (P = .0015). Among the patients who received induction chemotherapy with vincristine, adriamycin, and dexamethasone (n = 162), the same difference in OS was seen between those in CR and those in PR before ASCT (P = .0016). CR after ASCT also predicted longer OS (P = .0135); however, patients with continued CR after ASCT had significantly higher OS after ASCT compared with patient with induced CR after ASCT who were in PR before ASCT (P = .0178). Multivariate analysis indicated that remission status pre-ASCT (CR vs PR) is a significant prognostic factor for predicting OS after ASCT (P = .012, Cox proportional hazard analysis; odds ratio = 2.83; 95% confidence interval = 1.25 to 6.37). We conclude that patients with MM who are in CR before ASCT have a better OS than those in PR before ASCT. Continued CR after ASCT may be an important prognostic factor as well. Our findings suggest that the development of more effective induction regimens, including novel antimyeloma agents to improve initial response, should be pursued to enhance clinical benefits post-ASCT.     

Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse. A Pediatric Oncology Group Study

We devised a plan of intensive chemotherapy to address the problem of inadequate results of treatment in children with acute lymphoblastic leukemia in first bone marrow relapse. Immediately after remission was induced with four conventional drugs, a two-week intensification course of teniposide and cytarabine was given to eradicate subclinical leukemia. Patients in remission were then treated for two years with rapid rotation of pairs of drugs that were not cross-resistant and periodic courses of the same agents used to induce remission. A second complete remission was induced in 31 of the 39 patients in whom response to chemotherapy could be assessed. The probability of maintaining bone marrow remission in these patients for one year was 0.38 +/- 0.19 (95 percent confidence interval); the two-year probability was 0.29 +/- 0.17. Seven patients completed the treatment program, five of whom have been in continuous second complete remission 17 to 20 months after the cessation of therapy. Children whose initial bone marrow remission lasted less than 18 months had significantly poorer responses to retreatment than did those with a longer first remission (P = 0.004). Intensive chemotherapy, as described here, may save half of the children with acute lymphoblastic leukemia in whom bone marrow relapse occurs after a relatively long initial remission.     

Acute promyelocytic leukemia is a distinct subset of acute myelocytic leukemia with unique clinicopathologic characteristics including longer duration of relapse free survival: experience in 13 cases.

Acute promyelocytic leukemia(APL) is a subtype of acute myelocytic leukemia(AML) associated with unique features such as the presence of atypical promyelocytes and bleeding tendency due to disseminated intravascular coagulation(DIC). In a retrospective study, we analyzed 96 cases of AML seen at our hospital between June, 1989 and December 1993. Thirteen cases of APL(14%) were identified and their clinicopathologic characteristics were analyzed. The 86 cases of other types of AML served as controls. The distinct clinicopathologic features of APL as contrasted to other types of AML included younger age of patients, shorter duration of symptom before diagnosis, higher level of albumin at presentation, and a higher proportion of patients having coagulation abnormalities (75 vs. 25%). Bone marrow cellularity was higher in APL when compared to other types of AML (100 vs. 90%, P = 0.013). Of 13 patients with APL, 4 died of bleeding/sepsis between days 2 to 4 after admission. Seven of 9 patients who received induction therapy achieved complete remission(CR). CR rate in APL was similar to other types of AML (78 vs. 64%, P = 0.743). Five of seven patients who achieved CR remain in continuous CR at 9+ to 42+ months. CR duration is significantly longer in APL when compared to other types of AML (P = 0.029). In conclusion, this study showed that APL is a distinct entity among subtypes of AML with clinically significant bleeding tendency and rapidly fatal course if untreated. With appropriate antileukemic therapy, CR can be achieved in the majority of patients and the patients show a longer duration of CR when compared to other types of AML.     

Acute nonlymphocytic leukemia with normal karyotype. Is its in vivo drug susceptibility age-dependent?

Nineteen patients with acute nonlymphocytic leukemia (ANLL) de novo who had no detectable chromosomal abnormalities received intensive remission induction chemotherapy. After the first chemotherapy cycle, ten of 14 (71%) patients aged 60 years or less entered complete remission (CR) whereas none of five patients aged more than 65 years attained CR. On the other hand, leukemia showed a drug resistance in three (21%) of the former patients and in four (80%) of the latter patients. One patient in each group died during induction. Generally, older ANLL patients have an inferior CR rate after chemotherapy and a poor prognosis. This has been explained by the facts that the risk of induction death increases and that specific chromosomal abnormalities associated with poor prognosis are considerably more frequent in older patients. Our data may indicate, however, that in ANLL with normal karyotype older patients show a low initial response rate because of drug resistance.