scholarly journals Long-Term Outcome of Peripheral Blood Autologous Stem Cell Transplantation (AutoSCT) for De Novo Acute Myeloid Leukemia in Patients Achieving First Complete Remission after One Vs Two Induction Courses: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1840-1840
Author(s):  
Arnon Nagler ◽  
Jacques-Emmanuel Galimard ◽  
Myriam Labopin ◽  
Didier Blaise ◽  
William Arcese ◽  
...  
Keyword(s):  
Complete Remission ◽  
Peripheral Blood ◽  
Research Funding ◽  
De Novo ◽  
Lower Percentage ◽  
Karnofsky Performance Score ◽  
Long Term Outcome ◽  
Transplantation Outcomes ◽  
Good Risk ◽  
First Complete Remission

Abstract Background: Achieving a first complete remission (CR1) is the primary goal in the treatment of AML and is an important prognostic factor for transplantation outcome in general and even more so for autologous transplantation (AutoSCT). However, there are no data for AutoSCT indicating whether the number of chemotherapy courses (1 vs 2) needed to achieve CR1 is of prognostic significance for transplantation outcome. Methods: Using the EBMT/ALWP registry, we compared transplantation outcomes of adult patients (pts) aged ≥18 years with de novo AML that underwent a peripheral blood AutoSCT in 2000-2019 in CR1 achieved following one vs two chemotherapy courses. The primary outcome was the Leukemia Free Survival (LFS). Multivariate analysis (MVA) adjusting for differences between the groups and knowns factors were performed using Cox's proportional- hazards regression model for outcomes. Results: 1825 pts were included: 1532 (84%) with one and 293 (16%) with two induction chemotherapies courses. Time from diagnosis to AutoSCT was 4.7 (3.9-5.8) vs 5.7 (4.7-7.1) months, respectively (p<0.001). Median follow-up was 7.9 (95% CI: 7.4-8.4) and 7.7 (95% CI: 7.0-8.6) years, respectively (p=0.8). Median year of transplant was 2005 (2002-2009) and 2004 (2002-2007), respectively (p<0.001). Median age was 49 (38-57) and 47 (36 -56) years (p=0.06); 54% and 57 % of both groups were male, (p=0.35). Cytogenetic risk as defined by the Medical Research Council (MRC) classification, differed significantly between the two induction groups (p<0.001). Patients with one induction had a higher percentage of favorable-risk than those with two inductions (18% vs 14%), and a lower percentage of adverse-risk cytogenetics (6% vs 13%), while 76% and 73%, respectively, had intermediate-risk cytogenetics (missing data-11percentage). Karnofsky performance score (KPS) > 90 was higher in pts receiving 1 vs 2 inductions, 71% and 58% of pts, respectively (p<0.001). The most frequent conditioning regimen for both groups was Busulfan (Bu) /Cytoxan (Cy) 50% vs 45% and Bu / Melphalan (Mel) 17% and 19%, respectively, for induction groups 1 and 2, respectively. Day 30 neutrophil engraftment incidence was 96% and 96.5%. Five -year non-relapse mortality (NRM) was 6.2% vs 6.0% for pts achieving CR1 with 2 vs 1 chemotherapy courses, respectively, and did not differ significantly (HR=1.31 (95% CI: 0.81-2.10), p=0.27). Five -year relapse incidence (RI) was higher :67.2% vs 52.3%, (HR=1.46 (95% CI: 1.25-1.72), p<0.001), while LFS and overall survival (OS) were lower for pts achieving CR1 with 2 vs 1 course of chemotherapy: 26.6% vs 41.7% (HR= 1.42 (95% CI: 1.22-1.66), p<0.001) and 36.2% vs 53.3%, (HR=1.48 (95% CI: 1.25-1.75), p<0.001), respectively (Figure). Other significant prognostic factors in MVA were adverse- compared to good risk cytogenetics and older age (per 10 years) for all AutoSCT outcome parameters including RI, NRM, LFS and OS; intermediate compared to good risk cytogenetics for RI, LFS and OS; female gender for RI and LFS ;and year of transplant for RI and OS. Conclusions: The five -year RI was higher and transplantation outcomes significantly inferior in pts with AML undergoing AutoSCT but who received two lines of chemotherapy to achieve CR1. Such pts may benefit from additional novel therapies in the conditioning or post-AutoSCT or be considered for allogeneic transplantation in an attempt to reduce their high RI and improve outcomes. Figure 1 Figure 1. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Huynh: Jazz Pharmaceuticals: Honoraria. Mohty: Takeda: Honoraria; Jazz: Honoraria, Research Funding; Astellas: Honoraria; Janssen: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Gilead: Honoraria; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding. Pigneux: Amgen: Consultancy; Sunesis: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

Prolonged Survival of a Patient with De Novo Acute Myeloid Leukemia (AML) and Trisomy 13 with Intensive Chemotherapy and Autologous Peripheral Blood Transplantation (PBSCT): A Case Report.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4519-4519
Author(s):  
Nitin D. Joshi ◽  
Alpesh Amin ◽  
Rajneesh Nath
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Bone Marrow Biopsy ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
De Novo ◽  
Trisomy 13 ◽  
Autologous Pbsct ◽  
De Novo Aml ◽  
First Complete Remission

Abstract Trisomies are uncommon cytogenetic abnormalities in patient with de novo AML. Survival of patients with trisomy 13 ranges from 0.5 to 14.7 months. We present the treatment outcome of a 71-year-old man with de novo AML and trisomy 13 who had PBSCT in first complete remission. A 71-year Puerto Rican male was diagnosed with AML in April 2003. His CBC showed WBC count 177 K/mm3, hemoglobin 10.3 gm/dl, platelets 43 K/mm3 and blast cells 75%. Flow cytometry revealed that the leukemic blasts were CD33, CD13, CD11c and CD56 positive but negative for CD34. Cytogenetics failed to yield any metaphases. Peripheral blood FISH studies revealed trisomy 13 positivity in 300 of 325 cells analyzed. Patient received induction chemotherapy with high dose Ara-c (HiDAC) 3g/m2 QD x 5 doses and mitoxantrone 80mg/m2 on day # 2. Bone marrow done day 28 post induction chemotherapy revealed residual leukemic blasts. Cytogenetics showed that one out twenty metaphases had trisomy 13 along with translocation t (9:18) (q34; q10). 11.9% of cells had trisomy 13 by FISH analysis. The patient then received a second cycle of chemotherapy with HiDAC at 2 g/m2 Q12 x 12 doses. Bone marrow biopsy on day 35 following reinduction chemotherapy revealed normocellular-regenerating marrow in remission and FISH was negative for trisomy 13. On the third cycle of chemotherapy, patient received Etoposide 11 mg/kg. Neupogen was started on day #3 and 10.3 x 106 CD34 positive cells/kg were collected. The patient then underwent autologous PBSCT using Melphalan 160 mg/m2 as the preparative regimen. On Day +87 and Day +182 post transplant, bone marrow biopsy showed complete remission with FISH negative for trisomy 13. The patient is still alive 27 months after initial treatment and 22 months post PBSCT. Autologous PBSCT in first complete remission for AML with trisomy 13 may provide a superior survival than chemotherapy alone.

scholarly journals Expression of the multidrug resistance-associated P-glycoprotein (P- 170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications [see comments]

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2394-2398 ◽  
Author(s):  
JE Goasguen ◽  
JM Dossot ◽  
O Fardel ◽  
F Le Mee ◽  
E Le Gall ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Glycoprotein P ◽  
Kaplan Meier ◽  
Prognostic Implications ◽  
First Complete Remission

Abstract Immunocytochemical detection of the multidrug resistance (MDR)- associated membrane protein (P-170) was performed at time of diagnosis in a series of 36 children and 23 adults with acute lymphoblastic leukemia (ALL) using two monoclonal antibodies JSB1 and C219. Immunophenotypes were obtained in all cases and karyotypes were analyzed in 37 cases. Detection with JSB1 or with C219 led to similar results in terms of positive cells and cases, but the intensity of staining was higher with JSB1. In the populations studied, the rate of first complete remission differed between MDR-positive and MDR-negative in adult patients only (56% v 93%, respectively, P = .05). Of the 16 MDR-positive patients who had presented a first complete remission, 13 (81%) relapsed, compared with 13 of 35 (37%) MDR-negative (P = .008) patients. A higher rate of relapse among MDR-positive compared with MDR- negative patients was observed in adults and in children taken separately (adults 100% v 46%; children 73% v 32%, respectively). The survival rates (Kaplan-Meier method) were significantly higher in MDR- negative compared with MDR-positive populations as a whole (P = .002) and among children (P = .05) and adults (P = .03) taken separately. Event-free survival curves followed this trend. The percentage of second complete remission was very low in the MDR-positive group (15%) compared with 38% for the MDR-negative group. These results were shown by multivariate analysis to be independent of age, immunophenotypes, and karyotypes and clearly show the importance of MDR phenotype detection in ALL.

Autologous Transplantation of Non-Cryopreserved Bone Marrow for the Treatment of High-Risk Adult Acute Lymphoblastic Leukemia in First Complete Remission.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5492-5492
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Giebel ◽  
Malgorzata Krawczyk-Kulis ◽  
Maria Sadus-Wojciechowska ◽  
Lucja Kachel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Hospital Stay ◽  
Lymphoblastic Leukemia ◽  
Autologous Transplantation ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
First Complete Remission

Abstract Autologous hematopoietic stem cell transplantation (HSCT) is a recognised option of post-consolidation therapy for adults with high-risk acute lymphoblastic leukemia (ALL) not having a donor. G-CSF-stimulated peripheral blood SCT results in faster recovery compared to cryopreserved bone marrow transplantation (BMT) and is currentlly used by the majority of centres. In the current study we analyze the feasibility of a new technique of autologous BMT, which does not require cryopreservation. 115 adult patients (median age 24.5 (16–53) years) with high-risk ALL in first complete remission (CR) were treated with autologous BMT between 1991–2004 in a single center using uniform standard operating procedures. Immune phenotype was as follows: proB 17%, preB 9%, common 44%, mature B 1%, preT 9%, mature T 19%. Initial WBC was >30 G/l in 30% of patients. 8% of patients were bcr/abl(+), 38% required >1 course of induction to achieve CR. Bone marrow was collected in general anaesthesia and further stored for 72 hours in 4degC without any processing and reinfused 24 hours after completion of myeloablative therapy. Conditioning regimen (CAV) consisted of cytarabine 2x1000 mg/m2 d. −3, −2, −1, etoposide 800 mg/m2 d. −3, −2, cyclophosphamide 60 mg/kg d. −3, −2. Median NC dose was 2.0 (0.9–10.8)x10e8, CD34+cell dose − 1.6 (0.4–15)x10e6/kg. Median recovery of ANC>0.5 G/l equaled 16(11–45) days, PLT>50 G/l – 16(10–53) days (11% patients received cytokines to stimulate NC recovery). Median duration of hospital stay since the date of BMT was 19(13–51) days. The OS rate at 10 years (median follow-up 6.5 years) equaled 57% (+/−5%), LFS rate − 47% (+/−5%). Three patients died within 100 days after ABMT of septic infections (non-relapse mortality rate − 2.6%). None of the analysed factors (age, WBC at diagnosis, immonophenotype, time to achieve CR) was found to influence the long-term outcome. We conclude that autologous transplantation of non-cryopreserved bone marrow after CAV conditioning is feasible for adults with high-risk ALL. The method is characterized by fast recovery, short hospital stay and low non-relapse mortality, and may constitute good alternative to autologous PBSCT.

Will a Peripheral Blood (PB) Sample Yield the Same Diagnostic and Prognostic Cytogenetic Data as the Concomitant Bone Marrow (BM) In Myelodysplasia? An International Study Comparing Cytogenetics and Interphase FISH Using Parallel PB and BM Samples

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2922-2922
Author(s):  
Athena M Cherry ◽  
Marilyn L. Slovak ◽  
Lynda J Campbell ◽  
Kathy Chun ◽  
Virginie Eclache ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Research Funding ◽  
De Novo ◽  
International Study ◽  
Chromosome Abnormalities ◽  
International Prognostic Scoring System ◽  
Second Phase ◽  
Interphase Nuclei ◽  
Interphase Fish

Abstract Abstract 2922 The myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by ineffective hematopoiesis and a highly variable clinical course, for which novel treatments are beginning to emerge. Conventional cytogenetic studies (CCS) of bone marrow (BM) are routinely used in clinical practice to detect abnormal clones in proliferating (metaphase) cells, identifying clonal aberrations in ∼50% of de novo MDS cases. Cytogenetics is also one of the key International Prognostic Scoring System (IPSS) components used to estimate overall survival and leukemia-free survival in MDS. Chromosome abnormalities may be quantified at presentation and during treatment by the use of fluorescence in situ hybridization (FISH) with DNA probes for specific chromosome loci (e.g., chromosomes 5, 7, 8 and 20) in non-proliferating (interphase) nuclei. However, it is not clear whether or not peripheral blood CCS will yield the same diagnostic and prognostic data as bone marrow CCS at disease presentation or whether patients without apparent chromosome abnormalities by CCS have “hidden” abnormalities that can be identified by interphase FISH. To answer these questions, 15 members of the International Working Group on MDS Cytogenetics agreed to perform CCS and FISH in parallel on both peripheral blood and bone marrow samples collected from MDS patients. To be certain that all participating sites scored and interpreted their individual FISH data in a similar fashion, a quality assurance (QA) study was completed with each site studying two identical test (proficiency) samples. Concordance among sites was very good to excellent allowing for the establishment of a standardized protocol with clear scoring criteria before patient samples were processed. In the second phase of the study, a total of 77 MDS patients were accrued to the study with 61% showing an abnormal karyotype. A FISH panel consisting of eight probe sets [-5/5q-, -7/7q-/der(1;7), +8/8q-, -11/+11/11q-/add(11q), 12p-/+21/t(12;21), -13/13q-, 17p- and 20q-/i(20q)/i(20p), Abbott Molecular, Inc.] was performed on both specimen types. While CCS was frequently unsuccessful (57.5%) in the PB specimens, FISH was informative (concordant with BM/PB CCS) in 92% of cases, with 49% of PB FISH demonstrating an abnormal clone. FISH was discordant in 4 of 77 BM and PB samples (5%), while CCS and FISH on BM and PB were discordant in 6 of 77 BM specimens (8%) and 6 of 73 PB specimens (8%). The data suggest that evaluation of interphase nuclei from PB on follow-up (non-diagnostic) FISH studies on MDS patients will be equally informative (and less costly and stressful) as a BM sample. Disclosures: Slovak: PerkinElmer: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership, Research Funding. Ohyashiki:Nippon Shinyaku Co., Ltd.: Research Funding.

scholarly journals Extramedullary Disease at Diagnosis of Acute Myeloid Leukemia Does Not Influence Outcome of Patients Undergoing Allogeneic Hematopoietic Cell Transplant in First Complete Remission

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2020-2020
Author(s):  
Fotios V. Michelis ◽  
Hans A. Messner ◽  
Naheed Alam ◽  
Vikas Gupta ◽  
Dennis Dong Hwan Kim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Occurrence of extramedullary (EM) disease at diagnosis of acute myeloid leukemia (AML) has been associated with increased risk of relapse and worse outcomes post-chemotherapy. There is minimal data in the literature concerning the association with outcomes following allogeneic hematopoietic cell transplantation (HCT). The purpose of this single-centre study was to retrospectively investigate the impact of EM disease at diagnosis on the outcome of 303 patients with AML in first complete remission (CR1) that underwent HCT during the time period 2000-2013. Median age at HCT was 51 years (range 18-71), 151 (50%) patients were female. Myeloablative conditioning (MAC) was used in 202 (67%) patients, reduced-intensity (RIC) in 101 (33%) patients. Donors were related for 194 (64%) patients, unrelated for 109 (36%) patients. Grafts were peripheral blood stem cells (PBSC) in 253 (83%) patients and bone marrow in 50 (17%) patients. Median follow-up of patients alive was 63 months (range 12-168). Cytogenetics at diagnosis were available for 263 (87%) of patients, of which 16 (5%) were favorable, 185 (61%) were intermediate and 62 (20%) were unfavorable risk (MRC classification). Primary induction failure prior to achievement of CR was seen in 67 (22%) patients. In vivo T-cell depletion was performed in 71 (23%) patients. A total of 124 patients (41%) underwent HCT during the years 2000-2006 and 179 patients (59%) during the years 2007-2013. EM disease at diagnosis was seen in 39 patients (13%), of whom 11 patients had CSF disease, 7 patients had gingival infiltration and 5 patients had leukemia cutis. Univariate analysis for overall survival (OS) demonstrated that EM disease at diagnosis had no influence (HR=0.96 for EM, 95%CI=0.60-1.51, p=0.85, Figure 1). Multivariable analysis for OS including the previously described variables verified this observation. EM disease did not influence cumulative incidence of relapse (CIR) on univariate analysis (HR=0.94 for EM, 95%CI=0.45-1.96, p=0.86, Figure 2), and this also was confirmed on multivariable analysis. Moreover, EM disease did not influence cumulative incidence of non-relapse mortality on both univariate (HR=0.94 for EM, 95%CI=0.53-1.66, p=0.83) and multivariable analysis. In conclusion, EM disease at diagnosis of AML in patients achieving CR1, does not seem to influence outcomes post allogeneic HCT. This is significant in the consideration of allogeneic HCT for the treatment of this unfavorable subtype of AML. We are unable to comment on whether a similar percentage of patients with EM disease versus without EM disease, achieve CR1. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Kim: Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding.

scholarly journals G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Acute Leukemia Patients in the First Complete Remission: A Registered Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan-Ru Ma ◽  
Xiaohui Zhang ◽  
Lanping Xu ◽  
Yu Wang ◽  
Chenhua Yan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Clinical Outcomes ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Haploidentical Transplantation ◽  
First Complete Remission

G-CSF-mobilized peripheral blood (G-PB) harvest is the predominant graft for identical sibling donor and unrelated donor allogeneic hematopoietic stem cell transplantation (HSCT) recipients, but it was controversial in haploidentical related donor (HID) HSCT. In this registry study, we aimed to identify the efficacy of HID G-PB HSCT (HID-PBSCT) for acute leukemia (AL) patients in first complete remission (CR1). Also, we reported the outcomes for the use of G-PB grafts in comparison with the combination of G-BM and G-PB grafts in HID HSCT recipients. Sixty-seven AL patients in CR1 who received HID-PBSCT were recruited at Institute of Hematology, Peking University. Patients who received haploidentical HSCT using the combination of G-BM and G-PB harvests in the same period were enrolled as controls (n=392). The median time from HSCT to neutrophil and platelet engraftment was 12 days (range, 9–19 days) and 12 days (range, 8–171 days), respectively. The 28-day cumulative incidence of neutrophil and platelet engraftment after HSCT was 98.5% and 95.5%, respectively. The cumulative incidences of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) were 29.9% (95%CI 18.8–40.9%) and 7.5% (95%CI 1.1–13.8%), respectively. The cumulative incidences of total and moderate-severe chronic GVHD were 54.9% (95%CI 40.9–68.8%) and 17.4% (95%CI 6.7–28.0%), respectively. The cumulative incidences of relapse and non-relapse mortality were 13.9% (95%CI 5.4–22.5%) and 3.4% (95%CI 0–8.1%), respectively. The probabilities of overall survival (OS) and leukemia-free survival (LFS) were 84.7% (95%CI 74.7–94.7%) and 82.7% (95%CI 73.3–92.1%) respectively. Compared with the HID HSCT recipients using the combination of G-BM and G-PB grafts, the engraftments of neutrophil and platelet were both significantly faster for the G-PB group, and the other clinical outcomes were all comparable between the groups. In multivariate analysis, graft types did not influence the clinical outcomes. Overall, for the patients with AL CR1, G-PB graft could be considered an acceptable graft for HID HSCT recipients. This study was registered at https://clinicaltrials.gov as NCT03756675.

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.

Allogeneic Stem Cell Transplantation after Conditioning with Treosulfan, Etoposide and Cyclophosphamide for Patients with Acute Lymphoblastic Leukemia (ALL) Not Eligible for TBI-Containing Regimens: A Phase II-Study on Behalf of the German ALL Study Group (GMALL) and the German Cooperative Transplant Study Group

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2461-2461
Author(s):  
Nicolaus Kröger ◽  
Martin Bornhäuser ◽  
Matthias Stelljes ◽  
Uwe Pichlmeier ◽  
Christoph Schmid ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
One Year ◽  
First Complete Remission

Abstract Total-body-irradiation (TBI) based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with acute lymphoblastic leukemia (ALL). Within a multi-center prospective phase II study we have investigated the toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide, and cyclophosphamide in patients with ALL. Inclusion criteria were complete remission, non-eligibility for TBI or patient’s wish to avoid TBI. Between July 2007 and August 2010, 50 patients with a median age of 46.5 years were enrolled at ten German centers. 74% of the patients were in 1. CR and 26% 2. or higher CR.The conditioning regimen consisted of treosulfan (12 g/m²) given intravenously on three consecutive days (-7, -6, and -5) plus etoposide (30 mg/kg BW) infused on day -4, and cyclophosphamide (60 mg/kg BW) intra­venously on day -3 and -2. GvHD prophylaxis consisted of ATG-Fresenius (Fresenius Biotech, Gräfelfing, Germany), 20 mg/kg on day -3, -2, and -1 for unrelated donors, and optional for matched related donors. All patients received cyclosporine A and short course methotrexate (days 1, 3 and 6). Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. Primary graft-failure was observed in three patients. The toxicity was moderate including VOD in four patients. Acute graft-versus-host disease (GvHD) grade II - IV and grade III/IV was noted in 53 % and 14 %, respectively. Chronic GvHD at one year was seen in 41 %, which was extensive in 14 %. After a median follow-up of 24 months, the cumulative incidence of non-relapse mortality (NRM) at one year was 8 %, and of relapse 36 % and 51 % at one and two years, respectively. Patients in first complete remission showed a 12-months relapse-rate of 23 % compared to 69 % in patients beyond first complete remission. After 24 months, the respective rates were 34 % compared to 92 %. The estimated 2-year disease-free and overall survival was 36 % and 48 %, respectively. Patients in first complete remission experienced a median DFS of 25.7 months versus 8.9 months in patients beyond first complete remission. The 12- and 24-months DFS-rates were 69 % and 50 %, respectively, compared to 23 % and 0 %, respectively. Overall, we conclude that a conditioning regimen containing treosulfan, etoposide, and cyclophosphamide resulted in a low NRM , but a high risk of relapse in 2. or higher complete remission. This regimen might represents an alternative therapy for patients with ALL in 1.complete remission who need allogeneic stem cell transplantation but are not eligible for total-body irradiation. (registered under NCT00682305) Disclosures Kröger: Medac: Research Funding; Fresenius: Research Funding; Pierre Fabre: Research Funding. Off Label Use: Treosulfan is not approved for stem cell transplantation. Kobbe:Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Medac: Other; Astellas: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Other.

Phase II Study of the Frontline Hyper-CVAD in Combination with Ofatumumab for Adult Patients (pts) with CD-20 Positive Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1295-1295 ◽  
Author(s):  
Koji Sasaki ◽  
Paul B. Koller ◽  
Hagop M. Kantarjian ◽  
Deborah A Thomas ◽  
Maria R. Khouri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Multiple Organ Failure ◽  
Research Funding ◽  
De Novo ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Multiple Organ ◽  
Free Survival ◽  
Minimal Residual

Abstract Background: The hyper-CVAD regimen is an effective frontline regimen for de novo adult ALL. Expression of CD20 was identified as an adverse prognostic factor, associated with a higher incidence of relapse, lower 3-year complete remission duration (CRD) and lower 3-year overall survival (OS) rate. The addition of rituximab to the hyper-CVAD regimen in pts with CD20-positive ALL (≥20% expression by multicolor flow cytometry - FCI) improved outcome with 3-year CRD and OS rates by 68% and 65%, respectively. Ofatumumab (HuMax-CD20) targets a membrane proximal small-loop epitope on the CD20 molecule and was found to be more potent than rituximab in promoting complement-dependent cytotoxicity in vitro. Ofatumumab's safety and efficacy has been proven in chronic lymphocytic leukemia. Therefore a combination of the hyper-CVAD regimen and ofatumumab may be associated with better response rates, higher 3-year CRD and overall survival rates. Methods: Pts with newly diagnosed ALL and pts who received one prior course of chemotherapy received 4 courses of hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin, dexamethasone; the odd courses 1, 3, 5, 7); ofatumumab was given on courses 1 and 3, and 4 courses of MTX-Ara-C (methotrexate-cytarabine; the even courses 2, 4, 6, 8); ofatumumab was given on courses 2 and 4. This treatment would be followed by POMP (6-mercaptopurine, MTX, VCR, prednisone) maintenance therapy for approximately 30 months, interrupted by intensifications months 6, 7 and 18, 19 with MTX/Pegylated asparaginase and hyper-CVAD-ofatumumab. Central nervous system prophylaxis with MTX and ara-C was administered. When indicated local radiotherapy was administered in patients with bulky mediastinal disease Results: To date 37 pts with de novo ALL and 4 pts in complete remission (CR) previously treated (2 with prior cycle of hyper-CVAD, 1 post fludarabine-cytarabine based regimen, 1 with cyclophosphamide and dexamethasone) have received a median of 6 cycles (1-8) of therapy. Median age is 46 years (32-71). Median WBC at diagnosis was 5.4 x 109/L (1 -202 x 109/L). CD20 expression above 20% was found in 27 pts (66%), between 10 and 20% in 3 (7%) and below 10% in 11 (27%). 2 pts (5%) had concomitant CNS disease at diagnosis. Among the 34 pts with evaluable baseline cytogenetic analysis, 20 (49%) were abnormal. All but one pt (97%) achieved a CR after cycle 1 (4 pts were in CR at the start); 1 pt died of septic shock and multiple organ failure at day 21 of cycle 1. Thirty-eight (95%) pts achieved minimal residual disease (MRD) negativity as assessed by FCI; of whom 23 (64%) achieved MRD negativity after induction. Ten (27%) pts did not receive the full 8 planned courses of induction-consolidation; 16 (43%) pts are receiving maintenance in CR; 4 (11%) pts finished all treatment; 5 (%) pts were referred to allogeneic stem cell transplantation due to multiple cytogenetic abnormalities and delay in achieving negative MRD. Median time to neutrophil and platelet recovery for cycle 1 was 18 and 22 days after induction chemotherapy, respectively. Grade ≥ 3 toxicity included increase of LFT's in 13 pts (32%), increase of bilirubin in 7 (17%), nausea/vomiting in 4 (10%), mucositis in 3 (7%), neuropathy in 3 (7%), and thrombotic events in 1 (2%). Febrile neutropenia episodes during induction and consolidation cycles were reported at rates of 67% and 89%, respectively. With a median follow up of 15 months (1-45), 35 pts are alive; 6 pts relapsed and one had molecular relapse only. Six pts died: 1 at C1D22 of sepsis and intracranial bleed; 1 at C3D17 of sepsis and multiple organ failure; 1 at maintenance C16D35 of sepsis; 1 of relapse post ASCT; 1 post salvage therapy for minimal residual disease relapse; 1 of progressive disease after relapse. The 2-year PFS and OS rates were 68% and 87% respectively. Conclusion: The combination of hyper-CVAD with ofatumumab is safe and highly effective in pts with CD20-positive ALL. Table 1. Patient characteristics and outcome N (%)/Median [range] N=41 Age (yrs) 44 [22-71] Sex Male 25 (61) Female 16 (39) PS 0-1 38 (93) 2-3 3 (7) WBC (x 109/L) 5.4 [0.7-201.7] CNS disease positivity 2 (5) CD20 + (%) 1-10 9 (22) 10-20 3 (7) >20 27 (66) Pos 2 (5) CG Diploid 14 (34) Abnormal 20 (49) IM/ND 7 (17) Response CR 37/38 (97) CR after induction 37/38 (97) MRD at CR 23/36 (64) MRD overall 38/40 (95) Early death 1 (3) Figure 1. Progression-free survival and overall survival Figure 1. Progression-free survival and overall survival Disclosures Cortes: Teva: Research Funding; BerGenBio AS: Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Chahoud:American Society of Hematology (ASH): Other: 2015 HONORS Award recipient. Verstovsek:Incyte Corporation: Research Funding. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. O'Brien:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding.

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