High-dose cytosine arabinoside and m-AMSA is effective therapy in relapsed acute nonlymphocytic leukemia.

1984 ◽  
Vol 2 (6) ◽  
pp. 545-549 ◽  
Author(s):  
J D Hines ◽  
M M Oken ◽  
J J Mazza ◽  
A M Keller ◽  
R R Streeter ◽  
...  
Keyword(s):  
Complete Remission ◽  
Maintenance Therapy ◽  
Median Time ◽  
Induction Therapy ◽  
Cytosine Arabinoside ◽  
Partial Remission ◽  
De Novo ◽  
High Dose ◽  
Acute Nonlymphocytic Leukemia ◽  
Consolidation Therapy

High-dose cytosine arabinoside ( HDARAC ) and 4'-(9 acridinylamino) methane sulfon -m-anisidine (m-AMSA) was administered as induction therapy to 40 patients with relapsed or refractory acute nonlymphocytic leukemia (ANLL) with the following results: 28 patients (70%) achieved complete remission, one patient achieved a partial remission; five patients died with hypoplastic bone marrows containing less than 5% blasts; four patients died with hypoplastic marrowing containing greater than 5% blasts; and three patients failed to achieve marrow aplasia and died without significant cytoreduction in percentage of blasts. Consolidation therapy was not used and maintenance therapy was given to less than 10% (three patients) of remission patients. The median duration of remission for all patients was 6.0 months and the median time for the complete remission patients exceeded eight months. This regimen has acceptable toxicity and the results are equivalent to those obtained from conventional induction therapy of de novo ANLL patients.

scholarly journals Follicular lymphoma: first - line selection criteria of treatment

2019 ◽  
Vol 91 (8) ◽  
pp. 75-83 ◽  
Author(s):  
E S Nesterova ◽  
S K Kravchenko ◽  
A M Kovrigina ◽  
E G Gemdzhian ◽  
L V Plastinina ◽  
...  
Keyword(s):  
Complete Remission ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
Partial Remission ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
Antitumor Response ◽  
Chop Therapy

Follicular lymphoma (FL) is a tumor that develops from the B cells of the germinal center; characterized by recurrent and remitting course of the disease, the transformation of a tumor into diffuse large B-cell lymphoma (DLBCL) is possible. In generalized lesions and progression of FL, the most commonly used courses are R-CHOP and R-B. The choice of therapy for different cytological types, clinical and laboratory parameters remains disputable. Aim. To analyze the clinical, laboratory, morphological parameters of patients with FL, who got R-B and R-CHOP therapy; determine the criteria for selecting induction therapy. Materials and methods. The study included 203 patients with FL from 2000 to 2018. R-CHOP treatment was initiated in 126 patients, 14 of whom later received high - dose therapy (HDT) (R-DHAP: rituximab, dexamethasone, cisplatin, cytarabine) without autologous stem cell transplantation (autoSCT), 21 - HDT with autoSCT; treatment of 89 patients was limited to courses of R-CHOP and maintenance therapy with rituximab, two patients (in whom the disease progressed, despite R-CHOP therapy) were assigned the mNHL-BFM-90 program. The efficacy of treatment on various treatment regimens was evaluated primarily by overall survival. Results and discussion. R-B. 77 patients received R-B therapy. Complete remission of the disease was achieved in 47/77 (61%) patients (3 of them later developed a relapse of the disease), partial remission was achieved in 15/77 (19%) patients, in 13/77 (17%) cases progression was recorded tumors. 70 patients had 1-2 cytological type of tumor, 6 patients - 3A cytological type. In cases of progression, 3 of 13 patients (46%) were diagnosed with 3A cytological type FL. Median observation (at the time of analysis) - 34 months. R-CHOP. 89 patients with FL received high - dose therapy with R-CHOP (6-8 courses) and maintenance therapy with rituximab. In 39 (44%) patients, the disease remained in remission, and in 50 (56%), a relapse of the disease developed. 50 patients had 1-2 cytological types, 39 - 3 cytological types. In cases of recurrence of FL, a 3A cytologic type (36%) was diagnosed in 18/50 patients. Median observation - 93 months. R-CHOP + HDT and autoSCT. 21 patients after the R-CHOP courses continued (due to insufficient antitumor response) high - dose chemotherapy (HDT) and auto-SCT were performed. In 18/21 (86%) cases, complete remission of the disease was achieved and maintained, in 3 (14%) cases relapse developed. 16 patients had 1-2 cytological types, 5 - 3 cytological types. Median observation - 81 months. R-CHOP + HDT without autoSCT. 14 patients started therapy under the R-CHOP program as induction therapy, but then (due to insufficient antitumor response), the treatment was continued according to the HDT without autoSCT. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. 10 patients had 2 cytological types of PL, 4 - 3 cytological types. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. Median observation - 80 months. 7-year OS of patients with FL on RB therapy was 89% (95% CI 75-99), on R-CHOP therapy - 85% (95% CI 73-90), on R-CHOP + HDT and autoSCT - 87% (95% CI 57-100), on R-CHOP + HDT without autoSCT - 82%. 7-year PFS of FL patients on RB therapy was 70% (95% CI 75-99), on R-CHOP therapy - 44% (95% CI 73-90), on R-CHOP + HDT and autoSCT - 74% (95% CI 57-100), on R-CHOP + HDT without autoSCT - 80%. Conclusion. The R-B is most effective in FL 1 and 2 cytological types. The cytological type does not correspond to the type of tumor growth: at 3A and 3A + 3B cytological types, nodular / nodular - diffuse and diffuse types of growth are found. When choosing an induction course, one should look at the cytological type of FL. A high proliferative activity index (according to Ki67) is a predictor of resistance to R-B therapy. The absence of an interfollicular T-cell reaction in tumor tissue FL is associated with tumor chemoresistance. The presence of the bulky factor is associated (in most patients) with the FLIPI index with values from 3 to 5, and is a predictor of a poor response to therapy. Patients with bulky, high (more than 35%) Ki67 index and FLIPI from 3 to 5 in the debut of the disease as the first line therapy, it is preferable to choose the R-CHOP mode, and in the absence of (after 4-6 courses) to complete or partial remission to continue conducting the HDT.

scholarly journals The role of timing of high-dose cytosine arabinoside intensification and of maintenance therapy in the treatment of children with acute nonlymphocytic leukemia

Cancer ◽  
1990 ◽  
Vol 66 (6) ◽  
pp. 1106-1113 ◽  
Author(s):  
William G. Woods ◽  
Frederick B. Ruymann ◽  
Beatrice C. Lampkin ◽  
Jonathan D. Buckley ◽  
Irwin D. Bernstein ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Cytosine Arabinoside ◽  
High Dose ◽  
Acute Nonlymphocytic Leukemia

High-dose cytosine arabinoside as the initial treatment of poor-risk patients with acute nonlymphocytic leukemia: a Leukemia Intergroup Study.

1987 ◽  
Vol 5 (1) ◽  
pp. 75-82 ◽  
Author(s):  
H D Preisler ◽  
A Raza ◽  
M Barcos ◽  
N Azarnia ◽  
R Larson ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Cytosine Arabinoside ◽  
Cell Mass ◽  
Leukemic Cells ◽  
Remission Induction ◽  
Poor Performance Status ◽  
High Dose ◽  
Acute Nonlymphocytic Leukemia ◽  
Anthracycline Antibiotic ◽  
Days Of Therapy

Sixty-seven patients with newly diagnosed acute nonlymphocytic leukemia (ANLL) who were considered to be poor candidates for treatment with cytosine arabinoside (ara-C)/anthracycline antibiotic therapy were treated with high-dose ara-C (HDara-C) remission induction therapy. Thirty-four of the 67 patients had a hematologic disorder before developing acute leukemia or had a history of exposure to marrow toxins, 23 patients were greater than 70 years old, and 10 patients had medical problems that were felt to be a contraindication to therapy with an anthracycline antibiotic. Forty-two percent of patients entered complete remission (CR), whereas 22% failed to enter remission because of persistent leukemia. Treatment was associated with substantial toxicity varying from nausea and vomiting to irreversible cerebellar toxicity. Thirty-four percent of patients died during therapy. Poor performance status, a low serum albumin, and a low platelet count were associated with death during remission induction therapy, whereas a high pretherapy leukemic cell mass and a large number of residual leukemic cells in the marrow after six days of therapy were associated with treatment failure due to persistent leukemia.

Therapy-Related Myeloid Neoplasms Following Treatment for Multiple Myeloma : A Single-Center Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4261-4261
Author(s):  
Amelie Boquoi ◽  
Soraya Magdalena Banahan ◽  
Judith Strapatsas ◽  
David Lopez y Niedenhoff ◽  
Guido Kobbe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Complete Remission ◽  
Median Time ◽  
Median Survival ◽  
Partial Remission ◽  
Research Funding ◽  
De Novo ◽  
Remission Status ◽  
Support Research

Introduction Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) comprise late complications following mutagenic treatment. Limited data is available on the outcome of patients (pts) developing therapy-related MDS and AML (tMDS, tAML) after treatment for multiple myeloma (MM). Methods From 1976 to 2011, 3814 pts were entered into the Düsseldorf MDS registry. We identified 200 pts with tMDS or tAML. Of those, 41 pts had also been diagnosed with multiple myeloma (mm-MDS/AML). We compared these 41 pts to pts with de novo MDS (n=3614) and to pts with tMDS with other underlying diseases (n=159, 55 pts with other hematological diseases (34.5%), 93 with solid tumors (58.5%) and 11 with other diseases (7%)). Patient characteristics Median time between MM diagnosis and the onset of MDS was 5.5 years (range 0-28.5 years). Median age at the time of diagnosis of mm-MDS/AML was 67.8 years (range 32.5-84.6 years). Of all 41 mm-MDS pts, 13 developed AML (32%). Median time to progression from MDS to AML was 5 months (range 0.5-68 months). According to the WHO classification of 2016, there were 7 MDS-SLD, 10 MDS-MLD, 1 MDS-RS SLD, 13 MDS-RS MLD, 7 MDS-EB I, 2 EB-2, 1 MDS del(5q). 58% of mm-MDS pts had a complex karyotype, mostly affecting chromosomes 5 (22%) and 7 (17%), less often affected were chromosomes 17 (13%), 20 (13%) and 21 (13%). At MDS diagnosis, 11 MM pts were in complete remission (22%), 29 pts showed partial remission (58%), and 10 pts a stable disease (20%). 84.4% of pts with mm-MDS/AML had received conventional chemotherapy, mostly anthracyclines and alkylating agents. 94.4% had received melphalan. 15% of pts had received novel agents including immunomodulatory drugs and proteasome inhibitors. Results Both mm-MDS pts and tMDS pts were significantly younger than de novo MDS pts, however, there was no age difference between mm-MDS and tMDS (mm-MDS: mean 67.8 years, range 32-85, tMDS: mean 64.3 years, range 21-85, p<0.05, de novo MDS: 71,9 years, range 18-105; p<0.05). Both mm-MDS pts and de novo MDS pts showed significantly more males than females (mm-MDS 67% male versus 33% female, de novo MDS 57% versus 43%, p<0.05) while tMDS pts showed an equal ratio (48% versus 52%). When we compared risk group distribution according to IPSS-R we found significantly fewer mm-MDS pts to be in the lower risk categories (p<0.05 for both mm-MDS versus t-MDS and mm-MDS versus de novo MDS). Both mm-MDS and tMDS pts had a significantly worse karyotype when compared to de novo MDS (p<0.05). More cell lineages were affected in mm-MDS and tMDS pts than in de novo MDS (p<0.05). 50% of mm-MDS pts were pancytopenic versus 26% of de novo pts (p<0.05). Hemoglobin levels were significantly lower in mm-MDS and tMDS pts than de novo MDS pts (p<0.05). mm-MDS pts showed significantly higher blast counts in the bone marrow than all tMDS (p<0.05). Progression to AML occurred significantly more often in mm-MDS pts. At 12 months we discovered 12% of de novo MDS pts to have transformed to AML, 19% of tMDS and 24% of mm-MDS. At 36 months, 20% of de novo MDS pts had transformed to AML, 34% of tMDS and 39% of mm-MDS (p<0.05). When mm-MDS pts transformed to AML their survival was very poor, however, not significantly different compared to mm-MDS without AML transformation (7 months versus 11 months, p>0.05). Median survival of de novo MDS pts was 32 months (CI 29.940 - 34.192, range 1-345 months). In contrast, median overall survival of both mm-MDS and all other t-MDS was significantly shorter with 13 months in both groups (p<0.05, mm-MDS: CI 5.262 - 20.692, range 1-99 months; tMDS: CI 10,016 - 15,939, range 0-160 months). Myeloma remission status had no impact on survival: pts in complete remission showed a median survival of 6 months (95% CI, range 0 - 35 months), pts with partial remission 7 months (95% CI, range 5 - 9 months) (p>0.05). Conclusion Pts developing a myeloid neoplasm after treatment for multiple myeloma present with biological characteristics similar to those seen in pts with other tMDS. However, both clinical and molecular features are more severe with higher bone marrow blast counts, worse karyotypes, a more unfavourable IPSS-R score, and a significantly higher rate of transformation to AML. Yet despite a more aggressive phenotype, prognosis is equally poor and independent of myeloma remission status in mm-MDS/AML pts suggesting secondary myeloid neoplasia to govern the stem cell niche independent of previous disease or treatment. Disclosures Boquoi: Celgene: Other: Travel, Accommodation, Expenses; Janssen: Other: Travel, Accommodations, Expenses; BMS: Honoraria; Amgen: Honoraria, Other: Travel, Accommodations, Expenses. Kobbe:Takeda: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support; Medac: Honoraria, Other: Travel support; Jazz: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; Neovii: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support; Pfizer: Honoraria, Other: Travel support; Biotest: Honoraria, Other: Travel support; Celgene: Honoraria, Other: Travel support, Research Funding; Amgen: Honoraria, Other: Travel support, Research Funding. Gattermann:Takeda: Research Funding; Novartis: Honoraria; Alexion: Research Funding. Germing:Amgen: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria. Schroeder:Celgene Corporation: Consultancy, Honoraria, Research Funding. Fenk:Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria, Other: Travel, Accomodation, Expenses; Amgen: Honoraria; Celgene: Honoraria, Research Funding.

scholarly journals Midostaurin in Combination with Intensive Induction and As Single Agent Maintenance Therapy after Consolidation Therapy with Allogeneic Hematopoietic Stem Cell Transplantation or High-Dose Cytarabine (NCT01477606)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 322-322 ◽  
Author(s):  
Richard Schlenk ◽  
Konstanze Döhner ◽  
Helmut Salih ◽  
Andrea Kündgen ◽  
Walter Fiedler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
High Dose ◽  
Consolidation Therapy ◽  
Hematopoietic Stem ◽  
High Dose Cytarabine ◽  
Induction Cycle

Abstract Background: Internal tandem duplications (ITD) in the receptor tyrosine kinase FLT3 occur in roughly 25% of younger adult patients (pts) with acute myeloid leukemia (AML), implicating FLT3 as a potential target for kinase inhibitor therapy. The multi-targeted kinase inhibitor midostaurin shows potent activity against FLT3 as a single agent but also in combination with intensive chemotherapy. Aims: To evaluate the feasibility and efficacy of midostaurin in combination with intensive induction therapy and as single agent maintenance therapy after allogeneic hematopoietic stem cell transplantation (alloHSCT) or high-dose cytarabine (HIDAC). Methods: The study includes adult pts (age 18-70 years (yrs)) with newly diagnosed FLT3-ITD positive AML enrolled in the ongoing single-arm phase-II AMLSG 16-10 trial (NCT: NCT01477606). Pts with acute promyelocytic leukemia are not eligible. The presence of FLT3-ITD is analyzed within our diagnostic study AMLSG-BiO (NCT01252485) by Genescan-based fragment-length analysis (allelic ratio &gt;0.05 required to be FLT3-ITD positive). Induction therapy consists of daunorubicin (60 mg/m², d1-3) and cytarabine (200 mg/m², continuously, d1-7); midostaurin 50 mg bid is applied from day 8 onwards until 48h before start of the next treatment cycle. A second cycle is optional. For consolidation therapy, pts proceed to alloHSCT as first priority; if alloHSCT is not feasible, pts receive three cycles of age-adapted HIDAC in combination with midostaurin from day 6 onwards. In all pts maintenance therapy for one year is intended. This report focuses on the first cohort of the study (n=149) recruited between June 2012 and April 2014 prior to the amendment increasing the sample size; the amendment to the study is active since October 2014. Results: At study entry patient characteristics were median age 54 years (range, 20-70, 34% ≥ 60 yrs); median white cell count (WBC) 48.4G/l (range 1.1-178G/l); karyotype, n=103 normal, n=3 t(6;9), n=2 t(9;11), n=20 intermediate-2 and n=7 high-risk according to ELN recommendations, n=14 missing; mutated NPM1 n=92 (62%). Data on response to first induction therapy were available in 147 pts; complete remission (CR) 58.5%, partial remission (PR) 20.4%, refractory disease (RD) 15% and death 6.1%. A second induction cycle was given in 34 pts. Overall response after induction therapy was CR 75% and death 7.5%. Adverse events 3°/4° reported during the first induction cycle were most frequently gastrointestinal (n=34) and infections (n=81). During induction therapy midostaurin was interrupted, dose-reduced or stopped in 55% of the pts. Overall 94 pts received an alloHSCT, 85 in first CR (n=65 age&lt;60 yrs, n=20 age ≥60 yrs) and 9 pts after salvage outside the protocol or after relapse (n=70 from a matched unrelated and n=24 from a matched related donor). In pts receiving an alloHSCT within the protocol in median 2 chemotherapy cycles were applied before transplant (range 1-4) and the cumulative incidence of relapse and death at 12 months were 9.2% (SE 3.3%) and 19.5% (SE 4.8%). Maintenance therapy was started in 52 pts, 40 pts after alloHSCT and 12 pts after HIDAC. Only 4 adverse events 3°/4° were attributed to midostaurin. First analyses revealed a low cumulative incidence of relapse irrespective of the FLT3-ITD mutant to wildtype ratio (&lt;0.5 versus ≥0.5) in patients proceeding to alloHSCT with 12% and 5% as well as for those after HIDAC consolidation with 28% and 29%, respectively. Conclusions: The addition of midostaurin to intensive induction therapy and as maintenance after alloHSCT or HIDAC is feasible and compared to historical data may be most effective in those patients with a high FLT3-ITD mutant to wildtype ratio. Disclosures Schlenk: Novartis: Honoraria, Research Funding. Salwender:Celgene: Honoraria; Janssen Cilag: Honoraria; Bristol Meyer Sqibb: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Götze:Celgene Corp.: Honoraria; Novartis: Honoraria.

Early and Late Complications in 247 Adult Autologous Stem Cell Transplant Recipients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5242-5242
Author(s):  
Elisabetta Terruzzi ◽  
Chiara Scollo ◽  
Fausto Rossini ◽  
Matteo Parma ◽  
Pietro Pioltelli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Median Time ◽  
Partial Remission ◽  
Late Complications ◽  
Nutrition Support ◽  
Cardiac Complications ◽  
High Dose ◽  
Cell Transplant ◽  
Conditioning Treatment

Abstract High-dose therapy supported by autologous stem cell transplantation (ASCT) has became a widely applied therapy in many haematological malignancies during two decades. ASCT may be curative and even more commonly leads to prolonged survival. Along with the use of mobilised blood progenitor cells and improved supportive care after ASCT, the early treatment-related mortality (<100 d) has declined and is now in the order of 2–3%. Although relapse or progression of underlying malignancy is the most common cause of death in ASCT recipient, also late (>100 d) non-relapse mortality (NRM) occurs. We have analysed a cohort of 191 patients (108 male and 83 female) who received ASCT (247 transplant) in 1994–2005 in Bone Marrow Transplant Unit of San Gerardo Hospital. The median age was 49 years (16–70). The most common diagnoses included lymphoma (88), multiple myeloma (67), acute leukemia (32), chronic lymphocitic leukemia (2) and myelodysplastic syndrome (2). At the time of transplant (247 transplant) 93 patients was in complete remission, 67 patients in partial remission and 86 patients in persistent/progression malignancies. The most common conditioning treatment ASCT included: Melphalan (200 mg/m2 or 140 mg/m2) in 55% of case, BEAM in 30%, Busulfan-Cyclophosphamide in 4%, others in 11% (Thiotepa- Cyclophosphamide, Busulfan-melpalan, Mitoxantrone-melphalan, TBI- Cyclophosphamide). The median dose of CD34+ reinfused was 5.21 × 10^6/kg (1.2–15 × 10^6/kg). The median time to achieve an absolute neutrophil count >0.5 × 10^9/l was 12 days (range 0–49) and to achieve a platelet count > 20 × 10^9/l was 19 (range 0–36). The median time of hospitalisation was 22 days (range 10–93). During hospitalisation 158 patients (63%) developed oral mucositis: 100 (53%) of them developed mucosites of grade 1–2, 58 (37%) of grade 3–4. High dose chemotherapy with BEAM was more toxic on the oral mucose than high dose of Melphalan alone. In 41% of patients total parenteral nutrition support was necessary. During hospitalisation 180 patients (73%) developed sepsis: possible infection 61%, Gram + 20%, Gram − 12%, miscellaneous 3%, fungi 2%, viral 1%, Pneumocistis Carinii 1%. Regimens including cyclophosphamide was responsible for most sepsis. 44 patients presented a positive antigenemia of Cytomegalovirus; all of them were seropositive for CMV before ASCT; only one case of primary infection was seen and this patient died after 55 days after ASCT. At 100 days from ASCT 173 patients were in complete remission, 53 of them had a relapse of hematologic malignancies in a median time of 1 year (range 51 days-6 year), 32 patients in partial remission and 35 patients in persistent/progression malignancies. The late complications were: cardiac (30%), hepatic (16%), renal (3%), gastrointestinal (12%), CNS (8%), other (MGUS, cataract, aseptic necrosis of bone, diabete)(31%). The most important cardiac complications were: atrial fibrillation, sinusal tachycardia, arrhythmia, pericarditis. 61 patients (32%) died after ASCT. Death was due to complications related to disease progression in 62% of patients. 25% of patients died from infections. Secondary malignancies (acute myeloid leukemia) were the cause of late non relapse mortality in 2 patients. Fatal cardiovascular complications were observed in 4 patients (acute myocardial infarction or cardiomyopatia most probably due to previous anthracycline therapy).

No Benefit of Combining Additional Compounds with Standard High Dose Cytarabine Consolidation: Results of the Prospective Randomized AML2003 Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 255-255 ◽  
Author(s):  
Stefani Parmentier ◽  
Martin Bornhäuser ◽  
Christian Thiede ◽  
Christoph Röllig ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Complete Remission ◽  
Induction Therapy ◽  
High Dose ◽  
Unrelated Donor ◽  
Consolidation Therapy ◽  
Event Free Survival ◽  
Long Term Outcome ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
The Impact

Abstract Abstract 255 Introduction: Standard treatment of acute myeloid leukemia (AML) comprises one or two cycles of chemotherapy to induce complete remission (CR) followed by postremission treatment in order to prevent relapse of the disease (consolidation therapy). In 2003, we initiated a prospective multicenter randomized trial to investigate the impact of different consolidation strategies on long-term outcome in AML patients ≤ 60 years. Consolidation options comprised upfront allogeneic stem cell transplantation (allo SCT) in aplasia after induction therapy, autologous SCT, and three cycles of standard high-dose-cytarabine-based consolidation. For patients receiving high-dose cytarabine, the main study aim was to evaluate the benefit of adding additional mitoxantrone and amsacrine to cytarabine consolidation. Design: From 2003 to 2009, 1182 patients (median age, 48 years; range 16–60 years) with untreated AML were randomly assigned at diagnosis to different consolidation strategies after classical 7+3 induction. According to the risk-adapted treatment strategy of the trial, cytogenetically or molecular intermediate-risk (IR) and adverse-risk (AR) patients should receive an allo SCT as consolidation treatment if an HLA-identical-sibling donor (IR) or HLA-matched related or unrelated donor (AR) was available. IR and AR patients with no available donor should receive autologous SCT. All favorable risk patients and patients with no available donor were scheduled for high-dose cytarabine based consolidation. Half of the patients were randomized for high dose cytarabine based consolidation. Half of the patients were randomized for high dose cytarabine alone while the other half received high dose cytarabine with the addition of amsacrine and mitoxantrone. Standard chemotherapy consisted of three cycles with high dose cytarabine (2 × 3 g/m2, day 1,3,5) whereas combined consolidation contained two cycles of MAC (cytarabine 2 × 1g/m2, day 1–6, mitoxantrone 10 mg/m2, day 4–6) plus one cycle of MAMAC (cytarabine 2 × 1 g/m2, day 1–5, amsacrine 100 mg/m2, day 1–5). In order to evaluate the effect of the two cytarabine based consolidation strategies, we determined overall survival (OS) and event free survival (EFS) using the method of Kaplan Meyer. Survival distributions were compared using the log rank test. Results: 1182 patients were randomized for further intervention (Arm A+B: n=582, 49.3%; Arm C+D: n=600, 50.7 %). Median follow-up was 41.4 months (95%-CI 39.3–43.6). A total number of 375 patients received allogeneic (n=322) or autologous SCT (n=53) and 807 patients were consolidated with cytarabine. Of these patients, 407 were randomized for cytarabine alone and 400were randomized to receive cytarabine plus mitoxantrone and amsacrine (MAC/MAC/MAMAC). Complete remission rate (CR) after second induction therapy was 59.1% (n=698). Between the four arms, there were no significant differences of the CR rates. Five-year OS of patients receiving high dose cytarabine alone was 47.1% (95%-CI 42.0–52.2%), for patients receiving MAC/MAMAC as consolidation therapy it was 46.8% (95%-CI 42.3–51.3%; p = 0.610). Three-year event free survival (EFS) was also not significant with 30.5% (95%-CI 26.6–34.4%) for patients receiving high dose cytarabine alone and 35.6% (95%-CI 31.7–39.5%; p = 0.059) for patients receiving MAC/MAMAC. Conclusions: According to our data, the addition of mitoxantrone and amsacrine to high dose cytarabine consolidation confers no benefit for treatment outcome in younger AML patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Treatment of acute nonlymphocytic leukemia: use of anthracycline- cytosine arabinoside induction therapy and comparison of two maintenance regimens

Blood ◽  
1979 ◽  
Vol 53 (3) ◽  
pp. 455-464 ◽  
Author(s):  
HD Preisler ◽  
Y Rustum ◽  
ES Henderson ◽  
S Bjornsson ◽  
PJ Creaven ◽  
...  
Keyword(s):  
Complete Remission ◽  
Induction Therapy ◽  
Cytosine Arabinoside ◽  
Remission Rate ◽  
Leukemic Cell ◽  
Remission Induction ◽  
Prior History ◽  
Acute Nonlymphocytic Leukemia ◽  
Remission Maintenance ◽  
History Of

Abstract Patients with acute nonlymphocytic leukemia were given remission induction therapy consisting of cytosine arabinoside and an anthracycline. Those patients who experienced complete remission received two courses of consolidation therapy and were randomized to receive maintenance therapy consisting of either daily chemotherapy with reinforcements every 3 mo or reinforcement therapy only every 6 wk. The overall complete remission rate was 66%, with 80% complete remission for previously untreated patients less than 60 yr of age who did not have a prior history of malignancy. Remission durations were the same for patients treated with both maintenance regimens. The major determinant for successful remission induction therapy was patient age, with older patients frequently succumbing to intercurrent infection. Documented leukemic cell resistance to the therapy employed was only rarely encountered. Once remission was achieved, age was no longer a determinant of patient survival, since duration of remission was independent of age. Remission durations were directly related to leukemic cell retention of cytosine arabinoside triphosphate. Hence therapy for acute nonlymphocytic leukemia can be divided into two separate areas: remission induction and remission maintenance.

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