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

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

Blood ◽

10.1182/blood.v128.22.338.338 ◽

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.

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Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study

Blood ◽

10.1182/blood-2010-03-273243 ◽

2011 ◽

Vol 117 (8) ◽

pp. 2358-2365 ◽

Cited By ~ 147

Author(s):

Shigeki Ohtake ◽

Shuichi Miyawaki ◽

Hiroyuki Fujita ◽

Hitoshi Kiyoi ◽

Katsuji Shinagawa ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Complete Remission ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Standard Dose ◽

Randomized Study ◽

Survival Rates ◽

Adult Patients ◽

High Dose ◽

Acute Myeloid

Abstract We conducted a multi-institutional randomized study to determine whether high-dose daunorubicin would be as effective as standard-dose idarubicin in remission-induction therapy for newly diagnosed adult patients younger than 65 years of age with acute myeloid leukemia. Of 1064 patients registered, 1057 were evaluable. They were randomly assigned to receive either daunorubicin (50 mg/m2 daily for 5 days) or idarubicin (12 mg/m2 daily for 3 days) in combination with 100 mg/m2 of cytarabine by continuous infusion daily for 7 days as induction therapy. Complete remission was achieved in 407 (77.5%) of 525 patients in the daunorubicin group and 416 (78.2%) of 532 in the idarubicin group (P = .79). Patients achieving complete remission received intensive postremission therapy that consisted of either 3 courses of high-dose cytarabine or 4 courses of standard-dose therapy. Overall survival rates at 5 years were 48% for the daunorubicin group and 48% for the idarubicin group (P = .54), and relapse-free survival rates at 5 years were 41% and 41% (P = .97), respectively. Thus, high-dose daunorubicin and standard-dose idarubicin were equally effective for the treatment of adult acute myeloid leukemia, achieving a high rate of complete remission and good long-term efficacy. This study is registered at http://www.umin.ac.jp/ctrj/ as C000000157.

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Efficacy and Safety of Decitabine in Combination with G-CSF, Low-Dose Cytarabine and Mitoxantrone in Pediatric Refractory and Relapse Acute Myeloid Leukemia and MDS-Raebt

Blood ◽

10.1182/blood-2018-99-117850 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5175-5175

Author(s):

Liyan Fan ◽

Aili Chen ◽

Yixin Hu ◽

Peifang Xiao ◽

Jun Lu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Complete Remission ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Low Dose ◽

Pediatric Patients ◽

Efficacy And Safety ◽

Hematopoietic Stem ◽

Grade Ii ◽

Acute Myeloid

Abstract Background: It is difficult for pediatric refractory and relapse acute myeloid leukemia (RR-AML) and MDS-RAEB/RAEBT patients to achieve complete remission (CR) and these patients develop recurrence and die of either disease progression or associated complications. The CAG regimen (cytarabine, aclarubicin and G-CSF) has been widely used in treating patients with MDS-EB and AML-MRC in Asia. Likely, Short term CAG derived regimens called low dose induction therapy, MAG regimen (Mitoxantrone for 3 doses, cytarabine and G-CSF for 10 days) also showed efficacy in De Novo AML. However, MAG regimen showed less efficacy in RR-AML and MDS-5(5q-). Purpose: To evaluate the clinical efficacy and safety of low-dose decitabine in combination with low-dose MAG regimen (D-MAG regimen) in the treatment of RR-AML and MDS-RAEB/RAEBT. Method A total of 17 patients with MDS-RAEB/RAEBT and RR-AML((2 cases of MDS-RAEB, 3 cases of MDS-RAEBT, 10 cases for refractory AML, and 2 cases for relapse AML) from June 2017 to April 2018 in our center were included in the retrospective study. All the patients were treated with decitabine of 20 mg/m2 for 5 days and followed by 10 days of MAG regimen (cytarabine of 10mg/m2 q12h for 10 days, mitoxantrone of 5 mg/ m2.d for 3 days, and G-CSF of 5μg/kg.d for 10 days),called D-CAG regimen. After two cycles of induction chemotherapy, the patients who obtained CR received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results Among a total of 17 patients, the median age was the median age was 102 months (32-200 months) and 64.71 % of them were male. Characteristic features of these patients were illustrated in Table 1. Only 2 cases died of severe lung infection due to continuous agranulocytosis who had been received high dose induction therapy (Daunorubicin of 50mg/M2.d for 3 days, cytarabine of 100mg/m2 q12h for 10 days, and Etoposide of 150mg/m2.d for 5 days) for 2 cycles with poor physical condition before D-MAG. In the other 15 cases, 10 of them had complete remission (CR) after the first course of treatment, 4 cases were partial remission (PR), 1 case with a high blast cells at 25% indicated a poor response to D-MAG, and the effective rate was 93.3%. Among 4 children with PR, one case reached CR after the second courses of treatment. The most common adverse reactions in all children were hematological toxicity, grade III-IV. Liver damage was found in 2 cases, grade I and grade II respectively. There were 3 cases of oral side reactions, 1 case in grade I and 2 cases in grade II. The gastrointestinal reactions in all children were grade I - II. By July 2018, the median follow-up was 11 months (7-16months). Among 15 patients after D-MAG, 11 patients received HSCT. The twelve-month survival rate was 88.24% and the median leukemia-free survival (LFS) was 11 months. Conclusion The low-dose decitabine in combination with Low-dose MAG regimen improved CR rate for pediatric patients with MDS-RAEB and RR- AML, and is a promising treatment for pediatric patients with MDS/RR-AML. Disclosures No relevant conflicts of interest to declare.

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Results of intensive therapy in childhood acute myeloid leukemia, incorporating high-dose melphalan and autologous bone marrow transplantation in first complete remission

Blood ◽

10.1182/blood.v82.12.3730.bloodjournal82123730 ◽

1993 ◽

Vol 82 (12) ◽

pp. 3730-3738 ◽

Cited By ~ 1

Author(s):

K Tiedemann ◽

KD Waters ◽

GP Tauro ◽

D Tucker ◽

H Ekert

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Bone Marrow Transplantation ◽

Complete Remission ◽

Myeloid Leukemia ◽

High Dose ◽

Childhood Acute Myeloid Leukemia ◽

High Dose Melphalan ◽

First Complete Remission ◽

Acute Myeloid

Childhood acute myeloid leukemia (AML) has a poor prognosis with standard chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission improves the outlook only for the one third of patients with sibling donors. Autologous BMT with a lower morbidity and mortality is available to all. In this study, maximum cytoreduction was achieved by intensive early chemotherapy. Final intensification, with autologous BMT was offered to all those remaining in first complete remission (CR). Patients received two induction and two consolidation courses of intensively scheduled chemotherapy. Cytoreduction was assessed on day 14 and remission was assessed after courses 2 and 4. Bone marrow was harvested after recovery from the second consolidation course or after the first maintenance course and separated on a discontinuous percoll gradient before cryopreservation. Twenty-eight of 31 consecutively enrolled patients achieved CR. Three relapsed early and, of the 25 eligible, 24 underwent autologous BMT. Twenty-three patients received high-dose melphalan and 1 received busulphan and cyclophosphamide before autologous BMT at a median of 113 days (range, 86 to 301) after initial CR. Trilineage engraftment occurred in all. Neutrophil recovery to greater than 0.5 x 10(9)/L occurred at a median of 46 days (range, 13 to 92) after autologous BMT. Platelet recovery was delayed, with a median time to achieve greater than 20 x 10(9)/L of 42 days (range, 18 to 215). With a minimum follow up of 25 months following autologous BMT only 3 children have relapsed. The 5-year event-free survival rate (EFS) from diagnosis is 68% (95% confidence interval, 46% to 90%). Five- year EFS following autologous BMT is 87% (95% confidence interval, 67% to 100%). Autologous BMT with high-dose melphalan administration after intensive chemotherapy has produced EFS equivalent to allogeneic BMT and is associated with a strikingly low relapse rate. High-dose melphalan appears to be a valuable agent for conditioning therapy in AML.

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Clinical outcome of management of acute myeloid leukemia with idarubicin plus cytarabine

Annals of King Edward Medical University ◽

10.21649/akemu.v11i4.1100 ◽

2016 ◽

Vol 11 (4) ◽

Author(s):

Muhammad Hafeez ◽

Shaharyar , ◽

Khalid Shabbir ◽

Zafar Alauddin ◽

Muhammad Farooq ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Complete Remission ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Bone Marrow Examination ◽

Remission Induction ◽

High Dose ◽

Medical College ◽

A Prospective Study ◽

Acute Myeloid

A prospective study was conducted at Department of Clinical Oncology, King Edward Medical College / Mayo Hospital, Lahore from July 2003 to June 2004 to evaluate the effect of Idarubicin plus Cytarabine in chemo naive Acute Myeloid Leukemia (AML) patients. A total of 15 consecutive patients were enrolled with age group 15-58 years. Patients were classified according to French American British (FAB) classification. Induction therapy with Cytarabine as continuous infusion for 7 days and Idarubicin was given on day 1-3. For assessment of response, all patients were subjected to bone marrow examination fifteen days after completion of Induction chemotherapy. Consolidation Therapy with high dose Cytarabine was given on days 1, 3 and 5. Cytarabine was repeated after 28 days for 4 cycles in patients with complete remission after induction therapy. A remission induction rate of 66.7% was observed. Four patients died because of complications. One patient lost to follow up. Idarubicine and cytarabine is effective r egimen for achieving complete remission in AML Chemo-naive patients.

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Results of intensive therapy in childhood acute myeloid leukemia, incorporating high-dose melphalan and autologous bone marrow transplantation in first complete remission

Blood ◽

10.1182/blood.v82.12.3730.3730 ◽

1993 ◽

Vol 82 (12) ◽

pp. 3730-3738 ◽

Cited By ~ 40

Author(s):

K Tiedemann ◽

KD Waters ◽

GP Tauro ◽

D Tucker ◽

H Ekert

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Bone Marrow Transplantation ◽

Complete Remission ◽

Myeloid Leukemia ◽

High Dose ◽

Childhood Acute Myeloid Leukemia ◽

High Dose Melphalan ◽

First Complete Remission ◽

Acute Myeloid

Abstract Childhood acute myeloid leukemia (AML) has a poor prognosis with standard chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission improves the outlook only for the one third of patients with sibling donors. Autologous BMT with a lower morbidity and mortality is available to all. In this study, maximum cytoreduction was achieved by intensive early chemotherapy. Final intensification, with autologous BMT was offered to all those remaining in first complete remission (CR). Patients received two induction and two consolidation courses of intensively scheduled chemotherapy. Cytoreduction was assessed on day 14 and remission was assessed after courses 2 and 4. Bone marrow was harvested after recovery from the second consolidation course or after the first maintenance course and separated on a discontinuous percoll gradient before cryopreservation. Twenty-eight of 31 consecutively enrolled patients achieved CR. Three relapsed early and, of the 25 eligible, 24 underwent autologous BMT. Twenty-three patients received high-dose melphalan and 1 received busulphan and cyclophosphamide before autologous BMT at a median of 113 days (range, 86 to 301) after initial CR. Trilineage engraftment occurred in all. Neutrophil recovery to greater than 0.5 x 10(9)/L occurred at a median of 46 days (range, 13 to 92) after autologous BMT. Platelet recovery was delayed, with a median time to achieve greater than 20 x 10(9)/L of 42 days (range, 18 to 215). With a minimum follow up of 25 months following autologous BMT only 3 children have relapsed. The 5-year event-free survival rate (EFS) from diagnosis is 68% (95% confidence interval, 46% to 90%). Five- year EFS following autologous BMT is 87% (95% confidence interval, 67% to 100%). Autologous BMT with high-dose melphalan administration after intensive chemotherapy has produced EFS equivalent to allogeneic BMT and is associated with a strikingly low relapse rate. High-dose melphalan appears to be a valuable agent for conditioning therapy in AML.

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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 ◽

10.1182/blood.v124.21.2569.2569 ◽

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.

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

Blood ◽

10.1182/blood.v110.11.1852.1852 ◽

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.

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Filgrastim Administered after Early Assessment Bone Marrow Biopsy during 7+3 Induction Therapy for Acute Myeloid Leukemia Reduces Length of Hospital Stay

Blood ◽

10.1182/blood-2019-131293 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2607-2607

Author(s):

Jiasheng Wang ◽

Kirsten M Boughan ◽

Paolo F Caimi ◽

Brenda Cooper ◽

Marcos de Lima ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Induction Therapy ◽

Absolute Neutrophil Count ◽

Myeloid Leukemia ◽

Research Funding ◽

Cancer Center ◽

Early Assessment ◽

Treatment Start ◽

Acute Myeloid

Background National guidelines for acute myeloid leukemia (AML) therapy do not routinely recommend granulocyte colony stimulating factors (GCSF) during intensive induction therapy. Randomized trials have showed GCSF administration immediately after induction chemotherapy does improve time to absolute neutrophil count (ANC) recovery but is not associated with either improvements nor detriments to disease progression and survival. There are also concerns that GCSF may affect interpretation of bone marrow biopsy (BmBx) results. At the Seidman Cancer Center, GCSF has frequently been initiated AML patients (pts) undergoing induction chemotherapy after confirmation of hypoplasia in a day 14 BmBx (D14BM). Few studies have examined the potential role of GCSF initiated after confirmation of hypoplasia on D14BM. We hypothesized that this selective use of GCSF in (pts) with hypoplastic D14BM could improve short term outcomes from induction therapy. Methods Newly diagnosed adult AML pts receiving first-line inpatient induction therapy from 2003 through 2019 were retrospectively evaluated at the Seidman Cancer Center. Patients were included met criteria for hypoplasia on D14BM. Patients were stratified on whether they initiated GCSF within 5 days of the D14BM. Outcomes of interest included time from treatment start to discharge, number of febrile days, time to absolute neutrophil count (ANC) recovery to 1Î109 cells/L, effects on BmBx after count recovery, progression free survival (PFS) and overall survival (OS). Results We identified 121 patients meeting inclusion criteria. Patient characteristics are listed in Table 1. Patients receiving GCSF after D14BM were slightly more likely to be female, but overall groups were well balanced for age, race, performance status (PS), European Leukemia Net 2017 disease risk, baseline marrow blasts percentage and WBC, time from diagnostic biopsy to treatment, and specific induction regimen received. Within the GCSF after D14BM group, GCSF was started a median of 2 days (range 0-5) after D14BM. A median of 6 days of GCSF was administered in the intervention group. Patients receiving GCSF had inpatient hospital stay of 24 (95% CI 24-26) days versus 26 (95% CI 25-27) days (p = 0.0039) for those without GCSF after the start of induction therapy. Days to ANC recovery from start of induction was decreased in in the early GCSF group 23 (95% CI 22-24) vs 25 (95% CI 24-27) days (p = 0.008). There was no effect on platelet recovery, with a median of 23 versus 24 days, p = 0.53. Cox proportional hazard models were used to assess for impact of age, PS, Race, ELN risk, time to threat start, diagnostic marrow blasts percentage and WBC at time of treatment start. Only early GCSF remained significantly associated with time to discharge (Hazard ratio for discharge 1.70, 95% CI 1.02 to 2.82) or ANC recovery (Hazard ratio for ANC recovery 1.95, 95% CI 1.16 to 3.26). GCSF after D14BM was not associated with a reduction in febrile days (mean of 4.2 versus 3.3, p = 0.16). Subsequent BmBx to assess response did not have significantly increase marrow blasts for patients receiving GCSF after D14BM (mean 7.6% versus 1.4%, p = 0.08) nor was it associated with increased risk of refractory disease (Odds Ratio 1.4, 95% CI 0.46 to 4.46). Finally, early GCSF after D14BM did not result in significant changes in PFS (median 8.8 years versus 4.8 years, p = 0.24) or OS (median 9.1 years vs 4.8 years, p = 0.38). Conclusion For AML patients who achieve hypoplasia on D14BM during induction, GCSF administered after early assessment biopsy is associated with reduced time to ANC recovery and inpatient time. Interpretation of response marrows did not appear to be affected. Disclosures Caimi: Genentech: Research Funding; ADC Therapeutics: Research Funding; Celgene: Speakers Bureau. Malek:Janssen: Speakers Bureau; Medpacto: Research Funding; Sanofi: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Speakers Bureau; Adaptive: Consultancy. Metheny:Takeda: Speakers Bureau; Incyte: Speakers Bureau.

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Cladribine, Cytarabine and Mitoxantrone As Treatment Intensification for Patients with Acute Myeloid Leukemia with the Excess of Bone Marrow Blasts on Day 14 of the First Induction. Prospective, Multicenter Study By the Polish Adult Leukemia Group (PALG)

Blood ◽

10.1182/blood.v128.22.213.213 ◽

2016 ◽

Vol 128 (22) ◽

pp. 213-213 ◽

Cited By ~ 1

Author(s):

Agnieszka Pluta ◽

Kamil Brzozowski ◽

Konrad Stepka ◽

Ewa Wawrzyniak ◽

Anna Krawczynska ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Research Funding ◽

Risk Group ◽

Median Number ◽

Platelet Concentrate ◽

High Dose ◽

Treatment Intensification ◽

Acute Myeloid

Abstract Objectives The treatment results of acute myeloid leukemia (AML) patients (pts) younger than 60yo are still unsatisfactory. The strategy of double induction in AMLis based on two courses of chemotherapy depends on percentage of bone marrow (BM) blast at 7-14 days of treatment. This therapy intensification may induce higher response rate but toxicity appeared as early death (ED) rates still a medical dilemma. The advantage from addition of cladribine (2CdA) to standard induction and reinduction treatment was previously confirmed in PALG's trials. Aim The aim of this study was an estimation of efficacy and toxicity of treatment intensification based on BM blast at 14 day (D14) by second early induction, CLAM (2CdA + cytarabine + mitoxantron) Methods We performed multicenter, prospective, non-randomized trial where pts received DAC induction treatment with subsequent second early induction according as D14 BM biopsy results. When BM examination revealed >10% of blast without hypocellular marrowand pts met all criteria to intensive chemotherapy, second intensive induction with CLAM protocol (2CdA 5mg/m2 iv days 1-5, Cytarabine 2g/m2 iv days 1-5, Mitoxantron 10mg/m2 iv days 1-3) from day 16 was applied. The pts were allocated to risk-adjusted postremission treatment with high-dose cytarabine (HD-AraC) for low-risk group according to European Leukemia Net (ELN) classification and allogeneic stem cell transplantation (allo-SCT) recommended for intermediate and high-risk group. Results One hundred seventy one newly diagnosed AML pts from 8 PALG's centers were enrolled to the study. The median age was 47 yo (range19-60). According to WHO 2008 classification, our group consisted of 9% AML with recurrent genetic abnormalities, 19% AML related to myelodysplasia, 3% therapy-related AML and 69% AML not otherwise classified. Analysis of cytogenetic-molecular risk factors based on ELN classification revealed favorable, intermediate-1, intermediate-2, poor-risk groups in 17%, 44%, 18% and 21% AML pts, respectively. Twenty-six (15%) out of 171 pts had elevated BM infiltration of blasts at D14, with the median 44% (range 11-100%). Overall, 22 of 26 pts were judged as eligible to receive second induction, reasons for exclusion being in all cases active infection. Response evaluation was available in 150 pts, 21 pts were still ongoing in the protocol. Complete remission (CR) rate after single DAC induction course was 71% (n=106), partial remission (PR), non-remission (NR) and ED was 8% (n=12), 18% (n=28) and 3% (n=4), respectively. Response after double induction was evaluated in 21 out of 22 cases; one patient still has not reached time of measurement. CR was observed in 14/21 pts (67%), NR in 5% (n=1), ED 28% (n=6). The CR rate after inductiontreatment applied to first hospitalization (DAC or DAC+ CLAM) was 81% (n=120). Twelve pts who had <10% of blasts at day 14 and achieved PR after first induction were allocated to second DAC induction. Six out of them achieved CR leading to the overall CR rate 85%.In 27 pts who achieved CR allo-SCT was performed till June 2016, however there are pts who are still awaiting allo-SCT. The median duration of hospital stay was 31 (11-73) and 66 (52-76) days respectively for the DAC and the DAC + CLAM induction. During the single DAC induction the median number of days with neutropenia <0.5 G/l was 24 (12-101), and with thrombocytopenia <20 G/l was 12 (0-51). The median number of transfused packed red blood cell (PRBC) was 9 (0-32) and the number of platelet concentrate units was 15 (2-124). During DAC+CLAM double induction the median number of days of the neutropenia <0.5 G/l was 53 (17-73) and thrombocytopenia <20 G/l was 19 (4-57). The median number of PRBC was 18 (10-44) and the number of platelet concentrate units was 30 (5-153). With the median time of follow-up 16 months the median overall survival (OS) was not reached. The probability of 1-year OS was 59% and the probability of 1-year disease free survival was 83% (Figure 1, Panel A and B). Conclusion The preliminary results of our study suggest that early second induction CLAM is a feasible and effective treatment option in younger AML patients which further improves the CR rate and do not compromise the feasibility of allo-SCT. Disclosures Grzybowska-Izydorczyk: BMS: Honoraria; Novartis: Honoraria. Warzocha:BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Wierzbowska:Novartis: Consultancy, Honoraria; Janssen Cilag: Consultancy.

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