Microtransplantation Improves the Outcome of Older Patients With Newly Diagnosed Acute Myeloid Leukaemia: a Single-centre Study With Long-term Follow-up

Abstract Purpose: This retrospective single-centre study was to validate the efficacy and safety of microtransplantation (or micro-stem cell transplantation, MST) in the treatment of older patients with acute myeloid leukemia (AML).Methods: MST combines chemotherapy and human leukocyte antigen (HLA)-mismatched peripheral blood stem cell infusion without graft-versus-host disease (GVHD) prophylaxis. In total, 26 newly diagnosed AML patients were enrolled in our study from April 2008 to April 2018. The deadline date of follow-up was December 31, 2019. All of them received MST. Patients were divided into 2 age groups: 60~70 years (n=17) and >70 years (n=9). The outcomes of complete remission (CR) rate, overall survival (OS), leukemia free survival (LFS), hematopoietic recovery time, and treatment related toxicities were analyzed and summarized in this study.Results: 10 patients were still alive with complete remission (CR) at the deadline date, and the median overall survival (OS) was 64 months (range, 21-135 months). The CR, relapse and nonrelapse mortality rates were 84.6%, 38.5% and 30%, respectively. Both OS (p < 0.0001) and leukaemia free survival (LFS) (p < 0.0001) were significantly higher in the younger group than in the older group. The median times of neutrophil and platelet recovery were 12 days and 14 days, respectively. Conclusions: These data showed that MST could be an alternative treatment for older AML patients.

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A Randomized Clinical Trial of Lenalidomide and Dexamethasone with and without Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma: Interim Study Results,

Blood ◽

10.1182/blood.v118.21.4142.4142 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4142-4142 ◽

Cited By ~ 3

Author(s):

Lijun Dai ◽

Amy O'Sullivan ◽

Ryan Kennedy ◽

Mohammad Abbas ◽

Yongli Shuai ◽

...

Keyword(s):

Clinical Trial ◽

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Low Dose ◽

Progression Free Survival ◽

Newly Diagnosed ◽

Free Survival

Abstract Abstract 4142 Introduction: High dose chemotherapy combined with autologous stem cell transplantation (ASCT) as opposed to conventional chemotherapy improved progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM) and is currently the standard of care for newly diagnosed MM patients less than 65 years old. Over the last decade, novel agents such as lenalidomide or bortezomib have dramatically improved MM outcomes with similar response rates as ASCT and the role of upfront ASCT has become more controversial. Therefore the goal of this randomized clinical trial is to determine the role of upfront ASCT in newly diagnosed myeloma patients receiving novel agent lenalidomide and low-dose dexamethasone induction. Methods: Patients aged ≥18 years with newly confirmed, measurable MM in stage 2 and 3 (Salmon Durie) and meeting CRAB criteria were enrolled. Patients were randomized to transplant (Arm A) or to non-transplant (Arm B). Patients in Arm A received 4 cycles of lenalidomide (25mg days 1 – 21) plus low-dose dexamethasone (40mg days 1,8,15,22) followed by ASCT conditioned with 200 mg/m2 melphalan (LD+ASCT); Arm B patients received 8 cycles of lenalidomide plus low-dose dexamethasone (LD alone). Both arms received stem cell collection after 4 cycles of therapy if patients achieved at least a partial remission (PR). Patients with stable disease (SD) or progressive disease (PD) went off study. The primary objective was to compare best response. The secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS) and evaluation of secondary malignancies in both arms. Results: From February 2008 to May 2011, 44 patients with newly diagnosed MM were randomized. The patient characteristics were as follow: median age of the patients was 61.7 years (range 48∼75), 45.5% female and 55.5% male patients, ISS stage I 31%, II 51% and III 18%. 40 patients were eligible for evaluation and 20 patients were randomized to Arm A or Arm B, respectively. The data were analyzed according to latest IMWG response criteria (Blood. 2011 May 5;117(18):4691–5). In an intention to treat analysis, patients in Arm A (LD + ASCT), achieved a 100% Overall Response Rate (ORR) with 40% PR (n=8) and 60% Very Good Partial Response (VGPR) (n=12). In Arm B (LD only) the ORR was 75% (n=15), including 15% CR (n=3), 35% VGPR (n=7), 25% PR (n=5), 20% SD (n=4) and 5% PD (n=1). The ORR was significantly superior in the LD+ASCT group compared to LD alone (p=0.047). After a median follow-up of 25.3 months, 17 patients have PD (8 in LD+ASCT and 9 in LD alone), 6 have died (1 in LD+ASCT and 5 in LD alone). DOR, PFS and OS were not significantly different in both groups. OS showed a trend to be superior in patients treated with LD+ASCT (p=0.08). (Table 1). One patient in the LD+ASCT arm developed MDS 13 months after start of therapy. Conclusion: Our interim analysis of an ongoing clinical study suggests that treatment of newly diagnosed MM patients with lenalidomide plus low-dose dexamethasone induction followed by upfront ASCT resulted in significantly improved ORR. There was no difference in terms of DOR or PFS with a trend of superior OS in the LD+ASCT group. The study requires careful interpretation based on the low patient number and relatively short follow up, but supports the continued role of upfront consolidative ASCT in newly diagnosed MM patients. The incidence of secondary malignancy was low with the development of 1 MDS. Updated data on response and overall survival will be available at the time of presentation. Disclosures: Roodman: Amgen: Consultancy; Millennium Pharmaceuticals: Consultancy. Raptis:Millennium: Speakers Bureau; Celgene Corp: Speakers Bureau; Eisai: Speakers Bureau. Lentzsch:Celgene Corp: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; prIME Oncology: Honoraria; Imedex: Honoraria; Clinical Care Options: Honoraria.

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CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2017.77.6112 ◽

2018 ◽

Vol 36 (26) ◽

pp. 2684-2692 ◽

Cited By ~ 248

Author(s):

Jeffrey E. Lancet ◽

Geoffrey L. Uy ◽

Jorge E. Cortes ◽

Laura F. Newell ◽

Tara L. Lin ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Remission Rate ◽

Phase Iii ◽

Newly Diagnosed ◽

Secondary Acute Myeloid Leukemia ◽

Acute Myeloid

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

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Rituximab and Stem Cell Transplantation Produces Durable Remissions in Mantle Cell Lymphoma.

Blood ◽

10.1182/blood.v104.11.1390.1390 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1390-1390

Author(s):

Francisco J. Capote ◽

M. J. Pascual ◽

E. Gonzalez-Barca ◽

J. M. Bergua ◽

A. Jimenez ◽

...

Keyword(s):

Stem Cell ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Mantle Cell Lymphoma ◽

Cell Transplantation ◽

Cell Lymphoma ◽

High Dose ◽

Free Survival ◽

Mantle Cell

Abstract Introduction: Mantle cell lymphoma (MCL) is a CD20+ malignancy comprising up 5% of non-Hodgkin’s lymphomas, and has a poor prognosis under standard chemotherapy. The HyperCVAD-M/A regimen (fractionated high-dose cyclophosphamide, vincristine, doxorubicin and prednisolone alternated with methotraxate and cytarabine) has yielded encouraging results when combined with autologous stem cell transplantation (ASCT) in MCL, with 5-year failure-free survival of 54% and overall survival 72%. In an effort to improve these results further, we have combined rituximab in vivo purging and post-transplant consolidation with HyperCVAD-M/A plus ASCT. Methods: Patients aged <65 years with previously untreated or relapsed MCL were treated with four courses of HyperCVAD-M/A followed by four once-weekly doses of rituximab 375mg/m2 as purging prior to stem cell mobilization and harvesting, high-dose chemotherapy (ICT-CY or BEAM), stem cell reinfusion and four further doses of rituximab immunotherapy post-transplant. Results: Of the 34 patients enrolled so far, 15 (12 male, 3 female; 12 previously untreated) have been transplanted. The median age was 52 years (range 47–63 years). After the final post-ASCT immunotherapy all 15 patients were in clinical complete remission. With a median follow-up of 30 months from diagnosis (range 7–52 months), 14 patients remain alive with 13 in first complete remission. One patient died 15 months post-ASCT without evidence of disease recurrence. Kaplan-Meier estimates of 4-year overall and event-free survival are 93.3% and 86.6% respectively. Conclusions: This approach seems safe and feasible and produces durable remissions; longer follow-up of a more patients will be required to assess the effect of the procedure on survival.

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Conditioning with 8 Gy Total Body Irradiation and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia: Projected 4-Year Update.

Blood ◽

10.1182/blood.v108.11.3016.3016 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3016-3016

Author(s):

Matthias Stelljes ◽

Martin Bornhaeuser ◽

Matthias Kroger ◽

Joerg Beyer ◽

Maria C. Sauerland ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Myeloid Leukemia ◽

Dna Typing ◽

Relapse Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Unrelated Donors ◽

Total Body ◽

Acute Myeloid

Abstract Seventy-one patients with acute myeloid leukemia (AML), most of them (63/71) considered ineligible for conventional allogeneic hematopoietic stem cell transplantation (HSCT), were enrolled into a phase II study on reduced intensity myeloablative conditioning with fractionated 8 Gy total body irradiation (TBI) and fludarabine (120 mg/m2) (Blood. 2005 Nov 1;106(9):3314–21). Patients received mobilized peripheral blood stem cells (n=68) or bone marrow (n=3) from siblings (n=39) or unrelated donors (n=32). HLA-typing was performed for HLA-A, -B, -Cw (serological matching or intermediate resolution DNA typing), DRB1 and DQB1 (high resolution DNA typing). Three patients had unrelated donors with an allele mismatch in HLA DRB1 (2 with an additional mismatch in HLA Cw) and 7 patients were transplanted from unrelated donors with an antigen mismatch in HLA Cw. Thirty-six patients were transplanted in complete remission (CR) and 35 with untreated or refractory disease (non-CR). Median patient age was 51 years (range, 20–66). Sustained engraftment was attained in all evaluable patients. With a median follow-up of now 41.3 months (range, 20.4–70.4) in surviving patients, probabilities of overall survival for patients transplanted in CR and non-CR were 80% (95% CI, 66 to 94%) and 17% (95% CI, 5 – 29%) at 4 years, respectively. Relapse-free survival rates were 57% (95% CI, 39 – 75%) and 14% (95% CI, 2 – 26%). Of the 35 evaluable patients transplanted in CR, 10 patients suffered a relapse between days 68 and 868 after transplantation (cumulative incidence 29%). Five patients with late relapse (>1 year after transplantation) achieved a subsequent CR after conventional chemotherapy, blood stem cell boost and treatment with granulocyte-macrophage colony-stimulating factor, lasting 2000+, 1841+, 909+, 847+ and 480 days, respectively. Depending on donor type, relapse-free survival was similar in patients transplanted from unrelated or sibling donors. Overall survival in patients transplanted in complete remission from unrelated vs. sibling donors was 84% (95% CI, 73 – 95%) vs. 77% (95% CI, 68 – 86%). The cumulative incidence of non-relapse mortality (NRM) in CR patients was 11% at 4 years and beyond (3 patients deceased before day 100 and 1 patient 25 months after transplantation), but amounted to 37% at 4 years in non-CR patients. Nine of the 33 surviving patients (27%) have actually active chronic GvHD (5 limited and 4 extensive disease). This update confirms that allogeneic HSCT from related or unrelated donors with 8 Gy TBI/fludarabine conditioning is feasible with low NRM and preserved long-term antileukemic activity in AML patients in first or later CR.

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Autologous Bone Marrow Transplantation as an Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v110.11.5121.5121 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5121-5121

Author(s):

Andre S. Jung ◽

Asad Bashey ◽

Peter R. Holman ◽

Eva Carrier ◽

Januario Castro ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myeloid Leukemia ◽

Disease Free Survival ◽

Consolidation Therapy ◽

Free Survival ◽

Risk Patients ◽

Disease Free ◽

Acute Myeloid

Abstract Introduction: Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has been investigated as a potential therapeutic option to improve outcome in patients with acute myeloid leukemia. The optimal consolidation therapy for adults in remission without a histo-compatible donor has yet to be clearly established. Patients and Methods: This was a retrospective analysis of forty patients (23 females and 17 males) diagnosed with de novo acute myeloid leukemia, who were without a histo-compatible donor, that underwent APBSCT between the year 2000 and 2006 at a single institution. The patients’ age ranged from 18 to 73 with a median age of 50. Cytogenetic analysis was available on 37 of the patients. Complete remission (CR) was confirmed by bone marrow morphology and immunophenotype analysis by flow cytometry. Patients in remission were further consolidated with variable cycles of chemotherapy prior to stem cell transplantation. For stem cell mobilization, patients received high-dose cytarabine (2000mg/m2) and etoposide (5mg/kg) for three days followed by G-CSF at 10μg/kg, starting 10 days after the chemotherapy, before the peripheral stem cell collection. The preparative regimen prior to transplantation with unpurged stem/progenitor cells consisted of a combination of intravenous busulfan (0.8 mg/kg for 16 doses) and cyclophosphamide (60 mg/kg for two doses) (37 patients) or busulfan and melphalan (3 patients). Patients were then followed for treatment-related mortality, disease free survival, and overall survival. The analysis was stratified according to age, cytogenetic risk, and remission state. Results: There was no treatment-related mortality. Nineteen out of forty patients had relapse of their disease. The relapse rate was lowest in the low risk cytogenetic group who were under the age of 60 and highest in the high risk cytogenetic group who were over the age of 60. The overall 5 year survival for all patients was 47%. When stratified for cytogenetic risk and age, the overall survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 67%, 59%, and 75% respectively. The overall survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0% respectively. The projected rate of disease free survival at 5 years was 40%. When stratified for cytogenetic risk and age, the disease free survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 33%, 52%, and 50% respectively. Disease free survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0%. Comparing patients in CR1 versus patients in CR2, the overall survival was 47% in CR1 and 50% in CR2. The disease free survival, when grouped as above, were 41% for those in CR1 and 33% for those in CR2. Conclusion: APBSCT is a reasonable and safe intensive consolidation therapy for those patients without a compatible HLA matched donor in first or second complete remissions, notably for those under the age of 60 regardless of their cytogenetic risk. The number of standard consolidations prior to APBSCT may be an important variable predicting outcome.

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Prognostic Impact of 3q21 and 3q26 Cytogenetic Abnormalities in Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v120.21.2594.2594 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2594-2594

Author(s):

Mario Annunziata ◽

Piera Angelillo ◽

Laura Vicari ◽

Clelia Criscuolo ◽

Felicetto Ferrara

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Platelet Count ◽

Myeloid Leukemia ◽

Median Overall Survival ◽

Chromosome 3 ◽

Prognostic Impact ◽

Acute Myeloid

Abstract Abstract 2594 Background: Abnormalities affecting long arm of chromosome 3 are rare but recurrent in Acute Myeloid Leukemia (AML) and are detected in a variable percentage of AML patients according to different series. The 2008 World Health Organization classification recognizes AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) as a distinct subtype characterized by a poor prognosis. Allogeneic stem cell transplantation seems to improve outcome in eligible patients with these aberrations. Inappropriate expression of the ecotropic viral integration site 1 (EVI1) was demonstrated in virtually all patients with t(3;3)(q21;q26.2) and inv(3)(q21q26.2); as well as in a majority of patients with other 3q26 rearrangements. Other chromosome 3 abnormalities are rarely recognized in AML patients; clinical and prognostic relevance of these alterations is not yet defined. The aim of this study is to assess the prognostic impact of chromosome 3 abnormalities on disease characteristics and treatment outcome in AML. Patients and methods: A total of 580 consecutive adult patients were diagnosed with AML at our institution between February 2002 and July 2012. Conventional cytogenetic analysis performed on diagnostic bone marrow samples detected the presence of 3q abnormalities in 16 patients (2.7%). Two patients were lost to follow-up and were not evaluated for survival analysis. Molecular status of FLT3 and NPM1 was also performed and results are available for 10 patients. Median follow-up time for patients in this series was 47 months ( range 6–125). Results: There were 10 male and 6 female patients, the median age being 64.5 years (range 33–81), 10 patients had de novo AML while 6 evolved from a previously diagnosed myelodysplastic syndrome (MDS). Karyotype from MDS phase was available in 2 patients; both acquired 3q rearrangement at time of progression to AML. At time of diagnosis median haemoglobin value was 9.0 g/dL (range 4–11); median leucocyte count was 10.5 × 103̂/L (range 2.3 – 431). Median platelet count was 116 × 109̂/L (range 28 – 529), consistently with previous studies, which have shown that these patients present with higher platelet count at diagnosis when compared with no 3q rearranged ones. Regarding cytogenetic features 3 patients had t(3;3)(q21;q26), 3 patients had inv(3) (q21; q26), 3 patients showed a balanced rearrangement involving 3q26, while 6 patients harbored a del3q. One patient showed monosomy 3. Additional chromosomal changes were demonstrated in 5 patients, two of them had a complex karyotype (see Table 1), 3 had a monosomy 7. Thirteen patients out of 14 received intensive induction chemotherapy; complete remission (CR) was achieved in 5 patients (CR rate: 35.7%), the remaining 7 patients were resistant to induction as well as to salvage chemotherapy. Four patients underwent autologous stem cell transplantation. Median overall survival in this series is 5.5 months (range 0 – 20). At present only one patient is still alive and in CR, 20 months after diagnosis. Median disease free survival (DFS) for patients achieving a CR was 9 months (range 6–20). Median overall survival for patients resistant to first-line therapy was 3 months (range 0–6). Clinical features and treatment outcome of the patients are summarized in Table 1. Conclusions: The incidence of 3q abnormalities in our single institution series is 2.4%, in keeping with previous studies. Our findings confirm the association between these alterations and thrombocytosis at diagnosis, preceding MDS or multilineage dysplasia, presence in all FAB subtypes (except M3), association with additional chromosomal abnormalities as well as the poor response to conventional chemotherapy (CR rate 35.7%), and very short DFS in spite of obtaining CR. Disclosures: No relevant conflicts of interest to declare.

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Hematopoietic Stem Cell Transplantation (HSCT) Benefits the Survival of Acute Myeloid Leukemia (AML) Patients with IDH1, NRAS and DNMT3A Mutations

Blood ◽

10.1182/blood.v120.21.1981.1981 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1981-1981

Author(s):

Yang Xu ◽

Zhen Yang ◽

Hong Tian ◽

Huiying Qiu ◽

Aining Sun ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Gene Mutations ◽

Newly Diagnosed ◽

Hematopoietic Stem ◽

Acute Myeloid

Abstract Abstract 1981 Background: Gene mutations may serve as potential markers to extend the prognostic parameters in acute myeloid leukemia (AML) patients. In this study, we detected distribution of mutations in the nucleophosmin gene (NPM1), C-KIT, the fms-related tyrosine kinase 3 gene (FLT3), Isocitrate dehydrogenase gene 1 and 2 (IDH1, IDH2), the neuroblastoma RAS viral oncogene homolog (NRAS) and DNA methyltransferase 3A gene (DNMT3A) in 442 newly diagnosed AML patients (none-APL). Associations of gene mutations with clinical outcomes in these patients followed HSCT treatment or chemotherapy were further evaluated. Methods: Between February 2005 and December 2011, 442 newly diagnosed AML (none-APL) patients in our centre were retrospectively analyzed. There are 248 males and 194 females, and the median ages were 40 (16–60) years. 393 patients (88.9%) of patients were with single or normal karyotype and 49 patients (11.1%) were with complex abnormal karyotype. In addition to MICM examination, direct sequencing was employed to access the distribution of mutations in of FLT3-ITD (exon14), FLT3-TKD (exon 20), NPM1 (exon12), C-KIT (exon8, 17), IDH2 (exon 4), NRAS (exon1, 2), DNMT3A (exon23) of 445 AML patients. Complete remission (CR) was achieved in 258 patients (58.4%) followed the standard induction therapy, 128 patients received HSCT (Allo-HSCT: 121 vs. Auto-HSCT: 7) therapy after first remission or second remission while 258 patients received consolidation chemotherapy contained 4–6 cycles high dose Ara-C (HD-Ara-C). Overall survival (OS) and Event-free survival (EFS) were measured at last follow-up (censored), and Kaplan-Meier analysis was used to calculate the distribution of OS and EFS. Results: In 442 AML (None-APL) patients, 44 patients (9.7%) had C-KIT mutations, 97 patients (21.9%) had NPM1 mutations, 95 patients (21.5%) had FLT3-ITD mutations, 26 patients (5.9%) had FLT3-TKD mutations, 23 patients (5.2%) had IDH1 mutations, 48 patients (10.9%) had IDH2 mutations, 31 patients (7.0%) had DNMT3A mutations, and 40 patients (9.0%) had NRAS mutations. Using COX regression, we found that mutations in FLT3-ITD (HR:2.113; 95%CI: 1.1420 to 3.144),IDH1 (HR:3.023; 95%CI: 1.055 to 3.879), NRAS (HR:1.881; 95%CI: 1.021 to 2.945), and DNMT3A (HR: 2.394; 95%CI: 1.328 to 4.315) were independent unfavorable prognostic indicators of overall survival of AML patients. We further compared the outcomes of AML patients with such gene mutations followed different therapy (HSCT vs. HD Ara-C), and results shown that patients with mutations in IDH1, NRAS and DNMT3A received HSCT therapy had better survival. The median OS and EFS of patients with FLT3-ITD, IDH1, NRAS and DNMT3A in the two groups (HSCT vs. HD Ara-C) were as follows: IDH1 (OS: 35 months vs. 11 months, p=0.016; EFS: 34 months vs. 8 months, p=0.012), NRAS (OS: 27months vs. 8 months, p=0.008; EFS: 23 months vs. 4 months, p=0.049), DNMT3A (OS: 66 months vs. 19 months, p=0.008; EFS: 54 months vs. 13 months, p=0.002). Conclusions: Taken together, our data proved that mutant FLT3-ITD, IDH1, NRAS, and DNMT3A might serve as poor prognostic markers and hematopoietic stem cell transplantation as first-line treatment could favor the outcome of AML patients carrying IDH1, NRAS, and DNMT3A mutations. Disclosures: No relevant conflicts of interest to declare.

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Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.4554.4554 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4554-4554

Author(s):

Catherine Garnett ◽

Chrissy Giles ◽

Osman Ahmed ◽

Maialen Lasa ◽

Holger W. Auner ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Stem Cell Transplant ◽

Progression Free Survival ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

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WT1 Monitoring of Minimal Residual Disease (MRD) in Patients with Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v124.21.3695.3695 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3695-3695 ◽

Cited By ~ 1

Author(s):

Michele Malagola ◽

Crisitina Skert ◽

Enrico Morello ◽

Francesca Antoniazzi ◽

Erika Borlenghi ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myeloid Leukemia ◽

Research Funding ◽

Residual Disease ◽

Newly Diagnosed ◽

End Of Treatment ◽

Minimal Residual ◽

Acute Myeloid

Abstract Background: Although a complete remission (CR) can be achieved in 70-80% of newly diagnosed acute myeloid leukemia (AML) patients, relapses occur in up to the 50% of cases. Thus, minimal residual disease (MRD) monitoring is a major issue for early detection of patients at high-risk of treatment failure and relapse. Aim: to dynamically evaluate WT1 pan-leukemic molecular marker of MRD in patients with AML. Matherial and methods: 107 newly diagnosed AML patients consecutively treated between 2010 and 2013 were monitored with quantitative WT-1 from bone marrow (BM) and peripheral blood (PB) at baseline, after induction, after the first consolidation course, before allogeneic stem cell transplantation (allo-SCT), at the 3rd and the 6th month after transplantation Results: At diagnosis, 104/107 (97%) had increased PB and BM WT1 levels assessed according to the ELN assay. Eighty-eight out of 107 patients (82%) achieved a complete remission (CR) after induction, 30/88 (34%) relapsed during follow up and 24/107 (22%) were addressed to allogeneic stem cell transplantation (allo-SCT). By univariate analysis, PB-WT > 50x10^4/ABL and BM-WT1 > 250x10^4/ABL after induction (PB: p=0.02; BM: p=0.04), after consolidation (PB: p=0.003), at the end of treatment (PB and BM: p=0.001), at 3rd month of follow up (PB and BM: p=0.005) and at 6th month of follow up (PB: p=0.005) were associated with a reduced overall survival (OS). By multivariate analysis, a BM-WT1 > 250 x 10^4/ABL at the end of treatment was significantly associated with a reduced OS. In order to adapt the cut-off of WT1 in our series of patients, we considered WT1 levels as continuous variables and categorized them at approximately the 25th, 50th, and 75th percentile. A cut-off of PB-WT1 > 25x10^4/ABL and BM-WT1 > 125x10^4/ABL at the end of the treatment program was identified as correlated with reduced leukemia-free survival (LFS) and OS (p=0.001). Similarly, and restricting the analysis on the 24 patients allo-transplanted in CR, 8/11 (73%) with pre-transplant PB-WT1 ≥ 5 and 4/13 (31%) with PB-WT1 < 5 relapsed, respectively (p=0.04). The incidence of relapse was higher in AML patients with PB-WT1 ≥ 5 measured at 3rd (56% vs 38%; p=0.43) and 6th month (71% vs 20%; p=0.03) after allo-SCT. Interestingly, 5/5 (100%) patients with pre-transplant PB-WT1 ≥ 5 who never reduced this level at 3rd or 6th month after allo-SCT experienced a disease recurrence. Conclusions: our data, although retrospectively collected, show that WT1 monitoring may be useful to predict the relapse in AML patients. Acknowledgments: This work was supported in part by Banca di Credito Cooperativo di Pompiano e Franciacorta and Lions Club Bassa Bresciana Association. Disclosures Russo: Celgene: Research Funding; Gilead: Research Funding; Novartis: Consultancy.

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Event-Free Survival at 12 Months and Subsequent Overall Survival in Patients with Peripheral T-Cell Lymphoma

Blood ◽

10.1182/blood.v126.23.1501.1501 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1501-1501

Author(s):

Matthew J Maurer ◽

Fredrik Ellin ◽

James Cerhan ◽

Stephen Ansell ◽

Brian K Link ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Research Funding ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Newly Diagnosed ◽

Event Free Survival ◽

Free Survival ◽

T Cell Lymphomas

Abstract Background: Peripheral T-Cell lymphomas (PTCLs) constitute approximately 10% of lymphoid malignancies and consist of several distinct entities based on pathologic and clinical characteristics. With the exception of a few subtypes (e.g., ALK-positive anaplastic large cell lymphoma (ALCL) and some primary cutaneous or leukemic forms of PTCL), a majority of PTCLs are aggressive as characterized by poor treatment response, rapid disease progression and poor overall survival. We have shown that landmark timepoints of event-free survival after diagnosis can stratify subsequent overall survival (OS) in diffuse large B-cell and follicular lymphoma. Here we evaluate this approach in newly diagnosed aggressive PTCLs treated with anthracyline-based or related chemotherapy. Methods. Newly diagnosed PTCL patients were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2012. Clinical data were abstracted from medical records using a standard protocol. For this analysis, we included patients receiving anthracycline-based or other multiagent chemotherapy for the following PTCL subtypes: ALK-negative ALCL (N=24); angioimmunoblastic T-cell lymphoma (AITL, N=34); PTCL, not otherwise specified (NOS; N=60); enteropathy-associated T-cell lymphoma (EATL, N=8); extranodal NK/T-cell lymphoma, nasal type (ENKTL, N=11); and hepatosplenic T-cell lymphoma (HSTCL, N=1). Patients were prospectively followed, and event-free survival (EFS) was defined as time from diagnosis to progression, re-treatment, or death due to any cause. Landmark EFS timepoints were assessed at 12 (EFS12) and 24 (EFS24) months after the date of diagnosis. Subsequent OS was defined as time from a specific endpoint (diagnosis, event or EFS landmark). Replication was performed in a population-based cohort of T-cell lymphomas diagnosed from 2000-2009 from the Swedish Lymphoma Registry. Results. 138 eligible patients were enrolled in the MER from 2002-2012, the median age at diagnosis was 58 years (range, 19-88), 66% were male, 73% had Stage III-IV disease, and 33% had IPI 0-1. At a median follow-up of 47 months (range 11-120), 87 patients (63%) had an event and 70 patients (51%) had died. From diagnosis, only 60 patients were event-free at 12 months (EFS12 45%). Patients who failed to achieve EFS12 had a poor subsequent OS from event (median OS = 6.8 months, 95% CI: 5.3-14.0, figure 1). In contrast, patients who achieved EFS12 had a favorable subsequent OS (median unreached, figure 2). Of the 427 eligible patients in the Swedish registry, the median age at diagnosis was 66 years (range, 18-88), 63% were male, 68% had Stage III-IV disease, and 25% had IPI 0-1. PTCL subtypes were: ALK-negative ALCL (N=89); AITL (N=80); PTCL, NOS (N=183); EATL (N=44); ENKTL (N=24); and HSTCL (N=7). At a median follow-up of 86 months (range 40-158), 333 patients (79%) had an event and 316 patients (74%) had died. From diagnosis, 183 patients were event-free at 12 months (EFS12 44%). Similar to the MER cohort, Swedish patients failing EFS12 had poor subsequent survival (median OS = 3.7 months, 95% CI: 2.9-5.3, figure 1). Swedish patients achieving EFS12 had a favorable subsequent OS (median OS = 89 months, figure 2). Similar results were obtained when conducting landmark analysis at 24 months after diagnosis (EFS24). Conclusion. Relapse and re-treatment events within the first 12 months of diagnosis are associated with very poor OS in PTCL treated with anthracyclines or related chemotherapy, while patients achieving EFS12 have encouraging subsequent OS. Stratifying patients into prognostically distinct subsets using EFS12 may help focus biologic and biomarker studies. EFS12 has potential as an early endpoint for studies of newly diagnosed PTCL. Further investigation of determinants related to post-EFS12 survival is needed. Disclosures Maurer: Kite Pharma: Research Funding. Cerhan:Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Thompson:Kite Pharma: Research Funding. Relander:Respiratorius: Patents & Royalties: valproate for DLBCL.

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