Kinetics of Bone Marrow Blasts during Remission Induction Course in Acute Myeloid Leukemia: Effect on Complete Remission and Relapse-Free Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1852-1852
Author(s):  
Masamitsu Yanada ◽  
Guillermo Garcia-Manero ◽  
Farhad Ravandi ◽  
Stefan Faderl ◽  
Hagop Kantarjian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Persistent Disease ◽  
Bone Marrow Blasts ◽  
Acute Myeloid

Abstract Achievement of complete remission (CR) is crucial to prolong survival in acute myeloid leukemia (AML). The definition of CR has been well established; however, there are no objective measures for deciding when the probability of achieving CR has become so low that a patient’s disease can be considered resistant to therapy. In particular, it can be difficult to distinguish patients with resistant disease from those with persistent disease but who subsequently will enter CR, a distinction that underlies the decision to start a second course or change therapy. We attempted to facilitate this decision by examining the relation between the % marrow blasts 21 days, and later, after start of course 1 of initial induction therapy and the subsequent probability of CR on course 1. Our database consisted of the 593 adults with AML (≥20% blasts, acute promyelocytic leukemia excepted) who had bone marrow examined 21 days after beginning induction therapy including cytarabine at cumulative dose of 5–6 g/m2 at M. D. Anderson Cancer Center from 1995 to 2004. 340 of the 593 patients had an additional bone marrow examination between day 22 and day 28 (day 22–28) of course 1; similarly, day 29–35 marrows were done in 185 patients, day 36–42 marrows in 89 patients and so on. Bone marrows were categorized as morphologic leukemia-free state (MLFS; <5% blasts), persistent disease (PD; ≥5% blasts), or too few cells to count (TFTC). 197 of the 593 patients (33%) had an MLFS on day 21. This conferred a 94% probability of CR on course 1, independent of cytogenetic group. 275 patients (47%) had PD on day 21 and 57% of these 275 entered CR on course 1, with the probability of subsequent CR being predictable from the combination of cytogenetics, day 21 bone marrow blasts, and day 21 platelet and neutrophil counts. Patients with PD on day 21, but who achieved an MLFS on day 28 were highly likely to enter CR (40/47). However, those with PD beyond day 28 were very unlikely to enter CR on course 1, and no CR was observed in patients with PD after day 43. 121 patients (20%) had a TFTC marrow on day 21, with this finding associated with a CR rate of 72% on course 1 (p<0.001 vs MLFS, and p<0.001 vs PD). Not surprisingly given the respective CR rates, patients with MLFS on day 21 had significantly longer survival than patients with PD and patients with TFTC marrow (p<0.001). However, Relapse-free survival was not different among the 3 groups (p=0.109), which was also confirmed by multivariate analysis accounting for cytogenetics, antecedent hematologic disorder, and age. These results appear useful in management of AML, and recommend that bone marrow be examined on day 28, in patients with PD on day 21 and a <50% probability of subsequent CR and in patients with TFTC on day 21. Should PD persist on day 28, and especially on day 35, a second course should be started or new therapy instituted.

scholarly journals Increased Idarubicin Dosage during Consolidation Therapy for Adult Acute Myeloid Leukemia Improves Leukemia-Free Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 338-338
Author(s):  
Bradstock Kenneth ◽  
Emma Link ◽  
Juliana Di Iulio ◽  
Jeff Szer ◽  
Paula Marlton ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Consolidation Therapy ◽  
Advisory Committees ◽  
Free Survival ◽  
Acute Myeloid

Abstract Background: Anthracylines are one of the major classes of drugs active against acute myeloid leukemia (AML). Increased doses of daunorubicin during induction therapy for AML have been shown to improve remission rates and survival. The ALLG used idarubicin in induction therapy at a dose of 9 mg/m2 x 3 days (total dose 27 mg/m2) in combination with high-dose cytarabine and etoposide (Blood 2005, 105:481), but showed that a total idarubicin dose of 36 mg/m2 was too toxic in this context (Leukemia 2001, 15:1331). In order to further improve outcomes in adult AML by anthracycline dose escalation, we conducted a phase 3 trial comparing standard to an increased idarubicin dose during consolidation therapy. Methods: Patients achieving complete remission after 1 or 2 cycles of intensive induction therapy (idarubicin 9 mg/m2 daily x3, cytarabine 3 g/m2 twice daily on days 1,3,5 and 7, and etoposide 75 mg/m2 daily x7; ICE protocol) were randomized to receive 2 cycles of consolidation therapy with cytarabine 100 mg/m2 per day for 5 days, etoposide 75 mg/m2 for 5 days, and idarubicin 9mg/m2 daily for either 2 or 3 days (standard and intensive arms respectively). No further protocol therapy was given. The primary endpoint was leukemia-free survival from randomization to consolidation therapy (LFS) with overall survival (OS) as secondary endpoint. Results: A total of 422 patients with AML (excluding cases with CBF rearrangements or APL) aged 16 to 60 years were enrolled between 2003-10, with 345 (82%) achieving complete remission, and 293 being randomized to standard (n=146) or intensive (n=147) consolidation arms. The median age was 45 years in both arms (range 16- 60), and both groups were balanced for intermediate versus unfavorable karyotypes and for frequency of mutations involving FLT3-ITD and NPM1 genes. Of the randomized patients, 120 in the standard arm (82%) and 95 in the intensive arm (65%) received the second consolidation cycle (p<0.001). The median total dose of idarubicin received in the 2 consolidation courses was 36 mg/m2 (range 17-45), or 99% (47-125%) of the protocol dose in the standard arm, versus 53 mg/m2 (18-73), or 98% (33-136%) of the protocol dose in the intensive arm. The durations of grades 3-4 neutropenia and thrombocytopenia were significantly longer in the intensive arm, but there were no differences in grade 3 or 4 non-hematological toxicities. There were no non-relapse deaths during consolidation on the standard arm and 2 in the intensive (0% vs 1%; p =0.50). Subsequently, 41 patients in the standard arm and 37 in the intensive arm underwent elective allogeneic BMT during first remission. On intention to-treat analysis uncensored for transplant and with a median follow-up time of 5.3 years (range 0.6 - 9.9), there was improvement in LFS in the intensive arm compared with the standard arm (3 year LFS 47% (95% CI 40-56%) versus 35% (28-44%); HR 0.74 (95% CI 0.55-0.99); p=0.045) (Figure 1). The 3 year OS for the intensive arm was 61% (95% CI 54-70%) and 50% (95% CI 43-59%) for the standard arm; HR 0.75 (95% CI 0.54-1.05); p=0.092). Although adverse cytogenetics, presence of FLT3-ITD mutation, and absence of NPM1 mutation were all associated with poorer outcomes, there was no evidence of a benefit of intensive consolidation being confined to specific cytogenetic or gene mutation sub-groups. Conclusion: We conclude that in adult patients in complete remission after intensive induction chemotherapy an increased dose of idarubicin delivered during consolidation therapy results in improved LFS, without increased non-hematologic toxicity. Figure 1. Figure 1. Disclosures Szer: Ra Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alnylam: Honoraria, Membership on an entity's Board of Directors or advisory committees. Marlton:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wei:Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Abbvie: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Cartwright:ROCHE: Consultancy, Membership on an entity's Board of Directors or advisory committees. Roberts:Servier: Research Funding; Janssen: Research Funding; Genentech: Research Funding; AbbVie: Research Funding. Mills:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Meeting attendance sponsorship. Gill:Janssen: Membership on an entity's Board of Directors or advisory committees. Seymour:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Intensively timed induction therapy followed by autologous or allogeneic bone marrow transplantation for children with acute myeloid leukemia or myelodysplastic syndrome: a Childrens Cancer Group pilot study.

1993 ◽  
Vol 11 (8) ◽  
pp. 1448-1457 ◽  
Author(s):  
W G Woods ◽  
N Kobrinsky ◽  
J Buckley ◽  
S Neudorf ◽  
J Sanders ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Cancer Group ◽  
Acute Myeloid

PURPOSE Childrens Cancer Group (CCG) protocol 2861 was designed to test the feasibility of aggressively timed induction therapy followed by autologous or allogeneic bone marrow transplantation (BMT) as the sole postremission therapy for newly diagnosed children with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). PATIENTS AND METHODS Between April 1988 and October 1989, 142 patients were eligible for study. All patients entered received a timing-intensive five-drug induction of dexamethasone, cytarabine (Ara-C), thioguanine, etoposide, and daunorubicin (DCTER) over 4 days with a second cycle administered after 6 days of rest, irrespective of hematologic status at that time. Most patients subsequently received a second two-cycle induction course. Those who achieved remission were eligible for bone marrow ablative therapy with busulfan and cyclophosphamide, followed by 4-hydroperoxy-cyclophosphamide (4-HC)-purged autologous or allogeneic BMT rescue. RESULTS One hundred eight (76%) patients achieved remission: 19 (13%) died of complications of the leukemia and/or chemotherapy, and 15 (11%) failed to achieve remission. Seventy-four patients subsequently underwent BMT with either autologous (n = 58) or allogeneic (n = 16) rescue. For patients who received autologous rescue with 4-HC-purged grafts, the actuarial disease-free survival (DFS) rate at 3 years from the day of transplant is 51%, compared with 55% for patients who received allogeneic grafts (P = .92). At 3 years, the overall actuarial survival rate for all 142 patients entered on this study is 45%, with an event-free survival (EFS) rate of 37%. Adverse prognostic factors for outcome included an elevated WBC count or the presence of CNS leukemia at the time of AML diagnosis. CONCLUSION Results suggest that aggressively timed induction therapy followed by marrow ablation and BMT rescue with either autologous or allogeneic grafts for children with newly diagnosed AML or MDS is both feasible and effective.

Childhood acute myeloid leukemia: outcome in a single center using chemotherapy and consolidation with busulfan/cyclophosphamide for bone marrow transplantation.

1994 ◽  
Vol 12 (10) ◽  
pp. 2138-2145 ◽  
Author(s):  
P J Shaw ◽  
M E Bergin ◽  
M A Burgess ◽  
L Dalla Pozza ◽  
S J Kellie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Survival Rate ◽  
Complete Remission ◽  
Relapse Rate ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Free Survival ◽  
Acute Myeloid

PURPOSE To report the impact of bone marrow transplantation (BMT) with busulfan/cyclophosphamide (BuCy) as end consolidation in a cohort of consecutively diagnosed children with acute myeloid leukemia (AML). PATIENTS AND METHODS Between May 1987 and November 1992, 43 patients were diagnosed with AML. Tissue typing at diagnosis determined whether patients would proceed to autologous or allogeneic BMT as end consolidation after six cycles of chemotherapy. Conditioning for BMT was with BuCy, followed by allogeneic or unpurged autologous marrow infusion. RESULTS Of 37 patients who received chemotherapy, 35 achieved remission (95%) after one to six courses of treatment and 34 (92%) were transplanted. Five relapsed before BMT, four were subsequently transplanted in second complete remission (CR2) (n = 3) or untreated first relapse (n = 1), and one failed to respond to further therapy. All other patients proceeded to BMT in first complete remission (CR1). Eleven patients received allografts: one relapsed and one died of graft-versus-host disease (GvHD), for a leukemia-free survival rate of 90% at a median of 41 months after BMT (range, 3 to 60). For 23 autografts, there were two toxic deaths and eight relapses, with a leukemia-free survival rate of 61% at a median of 11 months after BMT (range, 0 to 66). The high relapse rate following autologous BMT led us to escalate the dose of Bu from 16 mg/kg to 600 mg/m2 using a single daily dose of Bu. CONCLUSION With modern supportive therapy, most newly diagnosed children with AML will enter remission and are eligible for intensification therapy. BuCy is well tolerated in children, which allowed us to escalate the dose of Bu in recent patients. Further follow-up is needed to determine whether this has an impact on the relapse rate following autologous BMT.

scholarly journals Kinetics of bone marrow blasts during induction and achievement of complete remission in acute myeloid leukemia

Haematologica ◽  
2008 ◽  
Vol 93 (8) ◽  
pp. 1263-1265 ◽  
Author(s):  
M. Yanada ◽  
G. Borthakur ◽  
F. Ravandi ◽  
C. Bueso-Ramos ◽  
H. Kantarjian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Kinetics Of ◽  
Bone Marrow Blasts ◽  
Acute Myeloid

Etoposide and mitoxantrone in newly diagnosed acute myeloid leukemia patients with persistent leukemia after a course of induction therapy with cytarabine and idarubicin

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7073-7073
Author(s):  
W. M. McHayleh ◽  
R. Redner ◽  
R. Sehgal ◽  
A. Raptis ◽  
M. Agha ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Median Duration ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Acute Myeloid

7073 Background: The goal of induction chemotherapy in acute myeloid leukemia (AML) is complete remission with restoration of normal bone marrow. If residual leukemia is present after the first course of induction therapy, patients receive a second course identical to the first or receive a non-cross resistant antileukemic regimen. Methods: In a retrospective study of adult patients with newly-diagnosed AML treated at the University of Pittsburgh Cancer Institute between December 2002 and May 2008, we evaluated the efficacy and toxicity of mitoxantrone (10 mg/m2/d) and etoposide (100 mg/m2/d), both administered intravenously within 5 days as second course therapy of patients not responding to first-course induction therapy with cytarabine and idarubicin. Univariate and multivariate associations between patient characteristics and complete response (CR) were assessed by logistic regression, with overall- and relapse-free survival estimated by Kaplan-Meier analysis. Results: 74 AML patients (mean age 56 years, range: 18–73 years) completed treatment with etoposide and mitoxantrone; 29 (39%) achieved CR. Lower CR rate was associated with unfavorable cytogenetic risk status at diagnosis and higher percent blasts prior to treatment with mitoxantrone and etoposide. Ten (14%) patients died due to infectious complications. No grade 3 or 4 hepatic toxicities were observed. One patient developed grade 3 cardiac toxicity. Median duration of neutrophil recovery following therapy in patients achieving CR was 29 days. Median overall survival was 9.0 months (95% CI 5.8–14.9 months). The 29 patients who achieved CR received postremission therapy: 16 of these eventually relapsed, while 4 others died without evidence of relapse. Median duration of relapse-free survival in these 29 patients was 11.0 months (95% CI: 9.0–19.3 months). Conclusions: Our study suggests that the combination of etoposide and mitoxantorne is an active and well-tolerated regimen as second-course therapy in newly diagnosed AML patients who have persistent leukemia after a first course of induction therapy with cytarabine and idarubicin. No significant financial relationships to disclose.

Homoharringtonine-Based Induction Regimens for Patients with De Novo Acute Myeloid Leukemia: A Multicenter Randomized Controlled Phase 3 Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 45-45 ◽  
Author(s):  
Jie Jin ◽  
Jianxiang Wang ◽  
Feifei Chen ◽  
Depei Wu ◽  
Jiong Hu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Phase 3 ◽  
Free Survival ◽  
Cytogenetic Profile ◽  
To Receive ◽  
Acute Myeloid

Abstract Abstract 45 Background Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukemia (AML), which have shown to improve the rate of complete remission (CR) and long-term survival. We aimed to further evaluate its efficacy and safety in treatment of de novo AML. Methods This phase 3 study was done in 17 institutions in China. Patients between the age of 14 and 59 with untreated AML were randomly assigned to receive HAA (homoharringtonine 2 mg/m2/day, days 1–7; cytarabine 100 mg/m2/day, days 1–7, aclarubicin 20 mg/day, days 1–7), HAD (homoharringtonine 2 mg/m2/day, days 1–7; cytarabine 100 mg/m2/day, days 1–7; daunorubicin 40 mg/m2/day, days 1–3) or DA (daunorubicin 40–45 mg/m2/day, days 1–3; cytarabine 100 mg/m2/day, days 1–7) regimen as induction therapy. Patients who achieved partial remission or had a decrease of blast ¡Ý60% could receive a same second induction course. All patients who had a complete remission were offered the same consolidation chemotherapy according to the cytogenetic-risk. The primary endpoints were CR and event-free survival (EFS). The trial is registered in Chinese Clinical Trial Register, number ChiCTR-TRC-06000054. Results 620 patients were randomly assigned to receive HAA (n=207), HAD (n=206) and DA (n=207) regimens. HAA or HAD regimen, as compared with DA regimen, resulted in a higher rate of CR in the first course of induction therapy (67.5% vs. 54.0%, P=0.005; 64.9% vs. 54.0%, P=0.026, respectively). The overall CR rate remained significantly higher in the HAA arm as compared with DA arm (75.0% vs. 61.9%, P=0.005). HAA or HAD regimen has similar rates of adverse events as compared with DA regimen, but was associated with significantly increased risk of induction death (5.8% vs. 1.0%, P=0.007; 6.6% vs. 1.0%, P=0.003, respectively). The EFS was greatly improved in the HAA arm (3-year EFS 35.4±3.5% vs.23.1±3.1%, P=0.002), while not significantly in the HAD arm (3-year EFS 32.7±3.5% vs.23.1±3.1%, P=0.078) as compared with the DA arm. Overall survival (OS) and relapse-free survival (RFS) did not differ significantly in the HAA or HAD arm as compared with DA arm, but an OS and RFS advantage of the HAA arm over the DA arm was observed in patients with favorable or intermediate cytogenetic profile (OS: P=0.014; RFS: P=0.022, respectively). Patients in the HAD arm with NPM1 but not FLT3ITD mutations, as compared with the patients in the DA arm, had an improved EFS (P=0.038). In intermediate cytogenetic profile, patients with mutant CEBPA had prolonged RFS in the HAA arm as compared with the DA arm (P=0.045). Conclusions Homoharringtonine-based induction regimens are associated with a higher rate of CR and improved survival as compared with DA regimen in AML. The toxicity is mild with the exception of a higher rate of induction death. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Achieving Early Remission By Induction Therapy Predicts a Favorable Outcome in Patients with Acute Myeloid Leukemia and an Intermediate Risk Karyotype Undergoing Allogeneic Stem Cell Transplantation in First Complete Remission

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2569-2569
Author(s):  
Philipp G. Hemmati ◽  
Theis H. Terwey ◽  
Il-Kang Na ◽  
Philipp le Coutre ◽  
Christian F. Jehn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Intermediate Risk ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Purpose: Acute myeloid leukemia (AML) is a highly heterogeneous disease. In addition to patient-related factors (co-morbidities, age, physical performance) and disease-specific variables (genetic risk profile) response to treatment is an important prognostic factor. In particular, the rapid achievement of hematologic remission by induction therapy was shown to predict overall outcome irrespective of the type of post-remission therapy employed. Here, we specifically investigated the impact of achieving early remission (ER), i.e. absence of leukemic blasts in the bone marrow at the end of the first course of induction therapy, as compared to delayed remission (DR) on the outcome of patients with AML who underwent allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1) at our center. Patients and Methods: We retrospectively analyzed 132 consecutive patients (ER: N=79, DR: N=53) with AML and an intermediate risk karyotype transplanted at our center between 1994 and 2013. Median age at alloSCT was 48 years. Before referral to transplantation, all patients were treated in a German multicenter AML trial. Patients aged <60 years were treated according to a double induction strategy, which consisted of one course of “7+3” followed by one course of high-dose cytarabine (HD-AraC) (3000 mg/m²). Patients aged ≥60 years were treated with a single course of “7+3”. In case of residual leukemic blasts, i.e. 5% or more in the bone marrow on day +16, first induction was followed by either one additional course of the same regimen or one course of HD-AraC (1000 mg/m2). Depending on the timing of alloSCT, one (N=78) or two (N=7) additional courses HD-AraC consolidation were given. For transplantation, myeloablative conditioning (MAC) (N=58) consisted of 12 Gy total body irradiation (TBI) and 120 mg/m2 cyclophosphamide (CY). Reduced-intensity conditioning (RIC) (N=74) consisted of fludarabine (FLU) 150 mg/m2, oral busulfan (BU) 8 mg/kg and anti-thymocyte globulin (ATG)(Fresenius®) 40 mg/kg. Transplants were from related (N=60) or unrelated (N=72) donors and were HLA-matched (10/10 antigens) (N=119) or HLA-mismatched (N=13) according to high-resolution molecular typing. Immunosuppression consisted of short course methotrexate (MTX) and cyclosporine in patients treated with MAC or cyclosporine and mycophenolate mofetil (MMF) in patients treated with RIC prior to alloSCT. Results: After a median follow-up of 56 (4-220) months for the surviving patients, 87 patients (66%) are alive and in CR. 26 patients (20%) relapsed after a median interval of 8 (1-133) months, whereas 19 patients (14%) died from NRM. Projected overall survival (OS) of the entire cohort after 1, 3, 5 and 10 years was 81%, 68%, 65%, and 61%. At the same time points the cumulative incidence of relapse (CI-R) or non-relapse mortality (CI-NRM) was 12%, 19%, 22%, and 22% or 13%, 13%, 13%, and 17%. In contrast to patients showing DR, patients achieving ER had a significantly higher 3-year OS and disease-free survival (DFS) of 76% versus 54% (p=0.03) and 76% versus 53% (p=0.03). Likewise, 3 years after alloSCT the CI-R was significantly lower in the ER subgroup as compared to patients achieving DR, i.e. 10% versus 35% (p=0.004). In contrast, NRM did not differ significantly between the ER and the DR subgroup. Multivariate analysis identified DR as an independent prognosticator for an inferior DFS (HR 3.37, p=0.002) and a higher CI-R (HR 3.55, p=0.002). Notably, there was no significant difference in OS, DFS, or CI-R between patients treated with MAC versus RIC in the ER or the DR subgroup. Conclusions: Taken together, these data indicate that rapid achievement of remission may predict a favorable outcome in patients with intermediate risk AML undergoing alloSCT in CR1. In turn, the adverse effect of DR may not be necessarily overcome by alloSCT. Disclosures No relevant conflicts of interest to declare.

Hyper-recovery of platelets after induction therapy is a predictor of relapse-free survival in acute myeloid leukemia

2016 ◽  
Vol 58 (1) ◽  
pp. 104-109 ◽  
Author(s):  
Etsuko Yamazaki ◽  
Heiwa Kanamori ◽  
Megumi Itabashi ◽  
Eriko Ogusa ◽  
Ayumi Numata ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Acute Myeloid

scholarly journals Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children's Oncology Group

Blood ◽  
2012 ◽  
Vol 120 (8) ◽  
pp. 1581-1588 ◽  
Author(s):  
Michael R. Loken ◽  
Todd A. Alonzo ◽  
Laura Pardo ◽  
Robert B. Gerbing ◽  
Susana C. Raimondi ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Oncology Group ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Relapse Risk ◽  
Acute Myeloid

Abstract Early response to induction chemotherapy is a predictor of outcome in acute myeloid leukemia (AML). We determined the prevalence and significance of postinduction residual disease (RD) by multidimensional flow cytometry (MDF) in children treated on Children's Oncology Group AML protocol AAML03P1. Postinduction marrow specimens at the end of induction (EOI) 1 or 2 or at the end of therapy from 249 patients were prospectively evaluated by MDF for RD, and presence of RD was correlated with disease characteristics and clinical outcome. Of the 188 patients in morphologic complete remission at EOI1, 46 (24%) had MDF-detectable disease. Those with and without RD at the EOI1 had a 3-year relapse risk of 60% and 29%, respectively (P < .001); the corresponding relapse-free survival was 30% and 65% (P < .001). Presence of RD at the EOI2 and end of therapy was similarly predictive of poor outcome. RD was detected in 28% of standard-risk patients in complete remission and was highly associated with poor relapse-free survival (P = .008). In a multivariate analysis, including cytogenetic and molecular risk factors, RD was an independent predictor of relapse (P < .001). MDF identifies patients at risk of relapse and poor outcome and can be incorporated into clinical trials for risk-based therapy allocation. This study was registered at www.clinicaltrials.gov as NCT00070174.

A Phase II Study of High Dose Lenalidomide as Initial Therapy for Acute Myeloid Leukemia in Patients > 60 Years Old.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 842-842 ◽  
Author(s):  
Ravi Vij ◽  
Alissa Nelson ◽  
Geoffrey L. Uy ◽  
Camille Abboud ◽  
Peter Westervelt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Disease Progression ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Low Dose ◽  
High Dose ◽  
Acute Myeloid

Abstract Abstract 842 Background: AML pts over the age of 60 years (AML ≥ 60) have a poor prognosis and warrant novel therapeutic approaches. Lenalidomide used at the approved starting dose of 10mg/day, with dose reductions for neutropenia/thrombocytopenia, has been shown to produce clinically significant unilineage erythroid responses in pts with myelodysplastic syndromes. However, even in these trials lenalidomide was shown to reduce the bone-marrow blasts. We hypothesized that using a higher potentially myelosuppressive fixed dose for induction therapy may be active in the therapy of AML ≥ 60 yrs. Methods: Eligibility criteria: untreated AML ≥ 60 with intermediate- or poor-risk cytogenetics (chromosome 5q- excluded), ECOG PS 0-2, and adequate organ function. Treatment included 2 cycles of high dose lenalidomide (50 mg/day) x 28 days (induction), followed by low dose lenalidomide (10 mg/day) × 28 days for an additional 12 months in non-progressing pts. The primary endpoint was complete remission (CR), including cytogenetic complete remission (CRc), morphologic complete remission (CRm) and complete remission with incomplete blood count recovery (CRi). Results: 33 pts were enrolled in this cohort, with a median age of 71 (range 60-88) years. 21 pts (64%) had intermediate risk and 12 (36%) poor risk cytogenetics. 23 pts (70%) had de novo AML and 10 pts (30%) had AML transformed from MDS/secondary to prior therapy. Median peripheral WBC at presentation was 4200 (range 600-44,000)/mm3. Median duration on therapy was 64 (range 3-267) days. Median follow-up from time of enrollment was 143 (range 6-401) days. In the intent-to-treat (ITT) population CR has been observed in 30%(10/33) and includes 3 CRc, 2 CRm, and 5 CRi. 45% (10/22) pts completing the entire 56 day induction regimen and 50% (10/20) pts with a presenting circulating blast count <1000/mm3 achieved CR. Responses were rapid with two pts confirmed to be in CR on day 15, five additional pts on day 28 and the 3 remaining pts on day 56. For the 7 pts that achieved a CR and had a clonal cytogenetic abnormality at diagnosis, 6 pts had resolution of the cytogenetic abnormality at the time of CR. Median CR duration was 5 (range 1 to ≥ 8) months, with 4 pts in CR currently remaining on low dose therapy at >8, >7, >7, and >4 months after achieving remission. No pt experienced bone-marrow aplasia according to biopsies performed on days 15, 28 and 56 of induction therapy. Median days of hospitalization were 6 (range 0-40). Reasons for treatment discontinuation were disease progression in 61%(20/33) and adverse events in 24%(8/33) and patient preference in 3% (1/33). The 60 day mortality was 27% (9/33) with 7 of these deaths due to disease progression. Treatment associated Grade (Gr) 3-4 hematologic toxicities included thrombocytopenia (67%), anemia (55%) and neutropenia (33%). Gr 3-4 febrile neutropenia occurred in 27%, pneumonia in 24% and bacteremia in 24%. Other Gr 3-4 non-hematologic toxicities in >10% of patients included fatigue (15%) and hypoxia (15%). Conclusions: High dose single agent lenalidomide represents a novel and effective therapeutic option with rapid onset of responses in older AML patients. Additional studies are needed to better understand the mechanism whereby lenalidomide induces CR in AML. Disclosures: Vij: CELGENE: Honoraria, Research Funding, Speakers Bureau. Off Label Use: LENALIDOMIDE IN ACUTE MYELOID LEUKEMIA. Fehniger:CELGENE: Research Funding.

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