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PubMed2005

[Clinical significance of detection of AML1/ETO fusion transcripts in childhood AML using real-time quantitative reverse transcription polymerase chain reaction].

This study was aimed to investigate the clinical value of quantification of AML1/ETO fusion transcripts using real-time reverse transcription PCR. Fourteen AML1/ETO positive children out of 52 AML children were selected. A serial dilution of AML1/ETO plasmid was used as a template for the AML1/ETO real-time PCR. AML1/ETO was quantified according to the expression of the GAPDH housekeeping gene at new diagnosis and during/after chemotherapy and transplantation. SPSS statistics was used to analyze the data. The results showed that the ratio of AML1/ETO: GAPDH expression level at new diagnosis varied in the range 0.219-2.080 (median 0.648) among the patients, without relevance with percentage of blasts. The detection sensitivity was up to the dilution of 1:10(5). Six patients showed a slight decline of AML1/ETO (higher than 5 x 10(-2)) at 1 month, three of whom relapsed in the early stage and one later. Five patients had a higher level than 5 x 10(-3) at 3 months, three of whom relapsed. Four patients with always a higher level than 5 x 10(-3) all relapsed in early stage. After six months, four out of them with constant low-level expression (10(-4) - 10(-6)) were in continuous complete hematological remission (CCR). In another patient, a rapid rise of AML1/ETO transcripts could be detected at CR stage and he relapsed 5 months later. The AML1/ETO gene expression leveling off by 10(-5) - 10(-6) could be detected in 3 patients at their complete remission after 9 months. It is concluded that real-time RT-PCR is a suitable approach for quantifying AML1/ETO transcripts in monitoring of AML patients with t(8;21) during/after chemotherapy and provides data of diagnostic relevance.

Acute Disease↗

PubMed1992

Longterm effects of prolonged maintenance and of very early intensification chemotherapy in AML: data from AMLCG.

In order to further improve the cure rate in AML we investigated the effect of more chemotherapy--in terms of its intensity and its duration--in 2 studies. In our 1981 study patients received TAD 1-2 courses for induction, 1 course for consolidation and randomly no further treatment or monthly myelosuppressive maintenance for 3 years. Evaluating 213 responders remission duration was clearly longer in the maintenance group with 24% CCR after 5 and 10 years. In our 1985 study the same successful strategy was further intensified by a second induction course given regardless of response to the first course to all patients up to 60 years of age while older patients received standard induction as before. This age-adapted concept resulted in a further increase of 5 years CCR in the 461 responders to as much as 34% not achieved for unselected patients in other multicenter trials. 20 patients receiving auto-BMT in first CR show the same relapse free survival as their counterparts receiving chemotherapy according to the 1985 protocol in a matched-pair analysis. We conclude that both very early intensification and prolonged maintenance contribute to a higher cure rate that is not further improved even by a maximum intensity short-term treatment. The limits of chemotherapy in AML may be overcome by modulating its myelotoxicity and antileukemic potency using GM-CSF as shown in 2 studies of our group.

Acute Disease↗

PubMed1992

Short term therapy (STT) for acute myelogenous leukaemia (AML).

Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.

Adolescent↗

PubMed1992

Randomized study of individualized induction therapy with or without VCR, and of maintenance of 4 or 12 courses in adult AML: JALSG-AML87. Japan Adult Leukemia Study Group (JALSG).

We asked 2 questions in this study. First was the additional effect of VCR in induction therapy, and the second was the duration of maintenance therapy. Adult AML were treated by an individualized response-oriented induction therapy with behenoyl Ara-C 200 mg/m2 daily + 6MP 70 mg/m2 daily + prednisolone 40 mg/m2 on days 1-4 + DNA 40 mg/m2 on days 1-3 and additionally on days 7, 8, 11, 12 (for M3, DNR 50 mg/m2 daily) (BHAC-DMP) until bone marrow became severely hypoplastic with less than 5% of blasts. Patients were randomized to BHAC-DMP or BHAC-DMP + VCR 0.35 mg/m2 on days 1-4. After obtaining CR, 3 courses of intensive consolidation therapy were given together with I.T. MTX+Ara-C+PSL. Maintenance intensification therapy was randomized to either 4 or 12 courses given every 2 months. Patients of age greater than or equal to 60 received about 2/3 reduced doses. From June 1987 to Sept. 1989, 265 consecutive adult AML were registered from 19 institutions and 258 were evaluable. Age ranged from 15 to 79 (med., 48). Out of 258, 200 (77.5%) achieved CR (80% in 209 of age less than 60 and 65% in 49 of age greater than or equal to 60). Unexpectedly, addition of VCR reduced the high CR rate of BHAC-DMP significantly (84% to 70%, p = 0.007). At the median follow-up of 37 mo., overall survival is 37%, and event-free survival (EVS) 27%. Survival, continuing CR and disease-free survival (DFS) rates of 200 CR cases are 45%, 40% and 35%, respectively. Patients received 12 courses of maintenance therapy showed better DFS (P = 0.0555). The VCR group had significantly worse EFS. By multivariate analysis, significant prognostic factors for the achievement of CR were age less than 60, PS 0-2 and no addition of VCR. Significant factors for longer DFS were induction of CR by one course, FAB M3 or M5 and age less than 50. The present multi-institutional study confirmed the high CR rates of the response-oriented individualized therapy reported from several centers in Japan, but failed to support an additional effect of VCR reported from one center.

Acute Disease↗

PubMed2005

[Application of reverse transcription-multiplex nested PCR to detect MLL rearrangement in AML-M4/M5].

OBJECTIVE: To explore the value of reverse transcription-multiplex nested PCR in detecting MLL rearrangement in lzAML-M4/M5. METHODS: Bone marrow chromosome preparation was made using direct method or short-term culture. Karyotypic analysis was carried out by R-banding technique. Five common MLL fusion genes and MLL partial tandem duplication in 40 AML cases, including 12 M4 and 28 M5 were detected by reverse transcription(RT)-multiplex nested PCR. RESULTS: R-banding karyotypic analysis revealed 11q23 translocation including t(6;11)(q27;q23), t(9;11)(p21;q23), t(11;17)(q23;q21) and t(11;19)(q23;p13.1) in 7 cases. MLL rearrangements consisting of MLL/AF6 (1 case), MLL/AF9 (1 case), MLL/AF17 (2 cases), MLL/ELL (2 cases) and MLL partial tandem duplication(2 cases) were detected in 8 cases by RT-multiplex nested PCR. Among 8 cases with MLL rearrangement, 6 were chromosome translocation, 2 were MLL partial tandem duplication. CONCLUSION: RT-multiplex nested PCR is a powerful technique in the detection of MLL rearrangement for tentativelly diagnosed AML-M4/M5.

Adolescent↗

PubMedDate not supplied

[Acute megakaryoblastic leukemia (AML-7) in a woman of 95 years].

Acute leukemia of megakaryocyte lineage (AML-7) is a rare entity defined by a blastic proliferation of which a part (>or= 50%) is represented by megakaryoblasts. We report the case of a 95 year old woman presenting a AML-7 secondary to a myelodysplastic syndrome (MDS), that represents an unusual form of MDS acutisation.

Aged, 80 and over↗

PubMed1991

[Therapy of acute myeloid leukemia in children--results of the AML II/87 multicenter study].

Fifty seven patients entered the cooperative study AML II/87 of the working group "Pediatric Hematology and Oncology" of East Germany. Two patients with initial hyperleukocytosis died prior therapy. 13 patients died within the first 4 weeks of therapy, 3 patients did not respond to therapy, and one patient is not yet in remission. 38 patients (70%) attained a complete remission. 15 patients get a bone marrow transplantation in first CR (10 autologous BMT without purging, 5 allogenous BMT). 12 of them are living and well 3 to 34 months after BMT. 9 of the 23 patients under chemotherapy relapsed, one patient is lost to follow up. 13 patients are living in continuous complete remission. The life table probabilities 48 months after the start of the protocol are 0.43 for disease free survival (DFS) and 0.60 for event free interval (EFI). The respective results of the former protocol AML I/82 were 0.34 for DFS and 0.47 for EFI.

Adolescent↗

PubMed1991

ABMT for children AML: Italian experience. GITMO-AIEOP Groups.

We report data from an Italian survey on ABMT in 93 AML children less than 14 years in 1st or 2nd remission performed in 15 Centers. Different conditioning regimens have been employed: BAVC, an original schedule of chemotherapy; TBI plus Cy and/or other drugs (TBI + CHT); other high dose chemotherapy schedules (HD CHT). 62 patients have been transplanted in 1st CR; 38 have been conditioned with BAVC, 16 with TBI + CHT and 8 with HD CHT. Relapses were 21 in the BAVC group (DFS = 35% at 66 months), 5 in the TBI group (DFS = 61% at 48 months) and 5 in the HD CHT group; overall DFS is 39% at 66 months. 31 patients have been transplanted in 2nd CR; 14 were conditioned with BAVC and 16 with TBI + CHT; 6 patients relapsed in the first group, DFS is 56% at 50 months; in the second group 2 early deaths and 3 relapses occurred, DFS is 65% at 65 months. 1 patient in 2nd CR, conditioned with HD CHT, died during aplasia. Overall DFS is 59% at 65 months. Although no final conclusions concerning ABMT in AML children may be drawn from this retrospective study because of heterogeneity of population and methods, results obtained in 2nd CR are clearly better to those obtained with standard chemotherapy alone, confirming the role of ABMT in this high risk category of patients.

Adolescent↗

PubMed1991

Follow-up study on bone marrow reticulin fibrosis in AML.

Planimetric analysis of argyrophilic (reticulin) fibers of the bone marrow was performed on 17 patients (7 males, 10 females, median age 52 years) with acute myeloid leukemia (AML). Trephine biopsies were investigated at presentation and during the course of chemotherapy. Density of reticulin was determined by examining the total marrow area as well as the hematopoietic tissue. In about half of the patients with FAB-subtypes M4, M5 an increased amount of fibers was recognizable on admission in comparison with age-matched controls. Two to five bone marrow biopsies (total 81) of each patient were obtained at intervals ranging mostly between three and seven weeks after cytotoxic treatment. The following results could be demonstrated: in several patients with a normal or elevated fiber count at onset, partial and complete remission was characterized by an increase in reticulin in the regenerative hematopoietic tissue. On the other hand, a relapse was most frequently heralded by a reduction of the formerly increased amount of fibers. Because of the inverse relationship between the density of argyrophilic fibers and the amount of fat cells, these findings were observable only by considering the hematopoietic tissue and not the total marrow area, as has been done in previous studies. For this reason a significant decrease in reticulin fibers in the areas of regenerative hematopoiesis may be suggestive of an impending relapse of AML.

Adult↗

PubMed1991

[Differentiation antigens on normal bone marrow cells and following culture with growth factors in patients with acute myeloid leukemia (AML)].

In an attempt to detect residual leukemic cells during complete remission (CR), we used 4 monoclonal antibodies detecting markers at different stages of myeloid maturation. Bone marrow cells of AML patients at diagnosis/relapse or in CR were compared with normal controls at day 0 and 7, after incubation with colony stimulating factors, by the alkaline phosphatase/antialkaline phosphatase method. In AML patients at diagnosis/relapse, the expression of the early differentiation markers (CD34, HLA DR) was significantly increased and that of the late marker CD15 significantly decreased at day 0. After day 7 liquid cultures, the markers HLA DR and CD13 were significantly increased and CD15 significantly decreased. During CR a significant increase in day 7 liquid cultures of the markers HLA DR and CD13 was found compared to normal controls. These results may reflect the proliferation in culture of residual leukemic cells in CR patients.

Adolescent↗

PubMed1991

Aclarubicin plus cytosine arabinoside versus daunorubicin plus cytosine arabinoside in previously untreated patients with acute myeloid leukemia: a Danish national phase III trial. The Danish Society of Hematology Study Group on AML, Denmark.

A regimen of aclarubicin (ACR) of 75 mg/m2 daily for 3 days plus a continuous intravenous infusion of cytosine arabinoside (ara-C) of 100 mg/m2 per day for 7 days was compared with daunorubicin (DNR) 45 mg/m2/day for 3 days plus ara-C for 7 days as first-line chemotherapy of de novo acute myeloid leukemia (AML) in a randomized, nationwide Danish study. A total of 180 patients aged between 17 and 65 years were entered onto the protocol. Patients who achieved complete remission (CR) were given five courses of intensive consolidation therapy consisting of two courses of high dose ara-C, two courses of amsacrine plus etoposide, and one course of DNR plus ara-C. Of 174 evaluable patients, 99 achieved CR. The rate of CR was significantly higher on ACR plus ara-C than on DNR plus ara-C [66% versus 50% (p = 0.043)] and decreased significantly with increasing age. The hematological toxicity was identical for the two regimens. A total of 83 patients entered consolidation therapy. At 4 years, 37% of patients with CR following ACR were still in remission compared with 33% following DNR (p = 0.48), and the total survival at 4 years was 29% versus 20% (p = 0.26). The duration of remission and total survival both decreased with increasing age. ACR plus ara-C seem at least as good or better than DNR plus ara-C as first-line chemotherapy of AML.

Aclarubicin↗

PubMed1989

Standard induction and low dose ara-C treatment in patients over 60 with AML or MDS.

In this retrospective study, 61 induction treatment periods in 57 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) were evaluated. According to the WHO performance status, 6 patients received no chemotherapy, 20 had low dose cytosine arabinoside (LD ara-C) induction courses, and 35 received standard induction consisting of daunorubicin and cytosine arabinoside. Untreated patients had a poor survival. Of the 20 patients with LD ara-C induction courses, 4 (20%) achieved complete remission (CR). Three patients (15%) died during induction. Of 35 patients with standard induction, 21 patients (60%) achieved CR. Toxicity was considerable - 11 patients (31%) dying during treatment. We conclude that patients over 60 yr of age with RAEB, RAEB-t or AML had a CR rate and survival comparable to those of younger patients if treated with standard induction chemotherapy at the cost of serious therapy-related complications. In patients who were judged not to be able to tolerate standard induction and who were subsequently treated with LD ara-C, complications occurred less frequently, but the CR rate was low and survival short.

Aged↗

PubMed1989

Retrovirus-neutralizing antibodies in AML and AMMoL patients: stage-specific distribution.

Plasma samples of patients with AML or AMMoL were tested for antibodies reacting with gp70 antigens of BaEV and GaLV as well as for antibodies neutralizing BaEV or GaLV. Both frequency and titer values of antibodies were higher in remission than in blastosis. Neutralizing activity could be detected only in those plasma samples which contained antibodies to the appropriate gp70 antigen. The data suggest the presence of retroviruses in humans as antigenic stimuli for the immune system in AML and AMMoL.

Antibodies, Viral↗

PubMed1989

[Multiple myeloma following chronic neutrophilia terminated with acute monocytic leukemia (AML, M 5 b)].

A case of a 70 years old female who developed multiple myeloma during a course of neutrophilia, and later on terminated with acute monocytic leukemia (AML, M 5 b) following Melphalan therapy for five years is reported. This patient was first found to have neutrophilia in 1966, After six years, she developed monoclonal gammopathy, (IgG1 kappa type) which coexisted with the neutrophilia. She was put on Melphalan regimen for 5 years which was discontinued due to anemia, leukocytopenia and the reduction of serum IgG. By routine bone marrow examination, she was diagnosed as AMoL (AML, M 5 b) in July 1984. Thereafter, a combination chemotherapy of BH-AC, 6-MP and prednisolone was started and complete remission for the AMoL was achieved after 2 months. Sixteen months later, she relapsed and a similar combination chemotherapy for reinduction regimen was administered. However, the AMoL was resistant and after 7 months, she died of pneumonia and multiple organ failure. The association of neutrophilia with multiple myeloma, the occurrence of AMoL after prolonged Melphalan therapy for the multiple myeloma and the strategy of therapy for secondary leukemia is discussed.

Aged↗

PubMed1987

[Allogeneic bone marrow transplantation in acute myeloid leukemia (AML): results in 14 patients].

Between February 1982 and August 1986 14 patients with AML (median age 24 years, range 10-41) underwent allogeneic bone marrow transplantation. 9 patients were grafted in first complete remission, 4 in first relapse, 1 in second relapse and 1 patient with refractory AML. Conditioning consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad). The patients received methotrexate (n = 12) or methotrexate and cyclosporine (n = 2) for prevention of graft versus host disease. Of the 14 patients, 7 are alive, 7 patients died. Causes of death were recurrence of leukaemia (n = 2), veno occlusive disease of the liver (n = 1), CMV-pneumonitis (n = 1), septicaemia (1), cerebral haemorrhage (1), acute graft versus host disease of the gut (1), necrotizing encephalopathy (n = 1). 7 patients are alive between 124 and 1784 days (median 671) in continuous complete remission. All patients but 1 have a Karnofsky-index of more than 80%.

Adolescent↗

PubMedDate not supplied

Detection of TdT in AML blasts by immunological and biochemical techniques.

The cellular level of terminal deoxynucleotidyl transferase (TdT) was measured in blasts from patients with AML. Parallel determinations were made using an immunoassay and polymerizing reaction. There was a good correlation between the two techniques (r = 0.92) and detectable levels of the enzyme was found in approximately 50% of the cases. The TdT levels found in AML blasts were 1/10 - 1/100 of that reported for cells of lymphoid origin.

DNA Nucleotidylexotransferase↗

PubMed1985

Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78.

One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by maintenance with thioguanine and cytosine arabinoside for two years and additional Adriamycin during the first year. One hundred nineteen (79%) patients achieved a complete remission. Thirteen (9%) children died of early hemorrhages. After a median follow-up time of 36 (12 to 57) months, 47 relapses have occurred, with CNS involvement in seven cases. The life table analysis revealed a probability for overall survival after almost five years of 45% (SD, 4%), for event-free survival 41% (SD, 4%), and for the event-free interval 52% (SD, 5%). Up to now, no relapse was seen after 2 1/2 years. Risk factor analysis showed that early fatal hemorrhages occurred predominantly in children with M5 FAB type and with initial leukocytosis. An initial high WBC count and liver enlargement were unfavorable parameters for achieving remission. No factors could be identified concerning the risk for relapse. These data indicate that the applied treatment strategy is successful in inducing complete remissions in about three fourths of children with AML and also in enhancing considerably the chances for long-term remission.

Adolescent↗

PubMed1984

Monoclonal antibodies differentiating between monocytic and nonmonocytic variants of AML.

Blast cells from 70 cases of acute myeloid leukemia (AML), with a preponderance of monocytic variants (M4 and M5), were stained with a panel of 10 monoclonal antibodies (MoAb) that react with normal myeloid cells. Two McAb, UCHMI and UCHALF, stained cells from nearly every case of M4 and M5 leukemia, but not cells from cases of M1/M2 leukemia. Two other antibodies, E11 and UC45, were also specific for the monocytic leukemias, but stained cells from a lesser proportion of cases. The antibodies TG1, OKM1, Smø, DA2, 28, and 5.5 stained a differing proportion of cases in both the M1/M2 and M4/M5 subtypes. Routine morphology and alpha-naphthyl acetate esterase (ANAE) staining were largely in agreement with the antibody findings, though the interpretation of the fluoride sensitivity of ANAE was apparently misleading in 10% of cases. It is concluded that these antibodies, particularly UCHMI and UCHALF, will be of considerable value in the more precise subtyping of AML and that some of this panel of antibodies will be valuable tools for the investigation of normal monocytic differentiation.

Antibodies, Monoclonal↗