A Comparative Study of the Outcome of High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation in Patients with High-Risk or Standard-Risk Myeloma Treated Concurrently,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4156-4156
Author(s):  
Syed Kazmi ◽  
Gary Lu ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Standard Risk

Abstract Abstract 4156 Background: Chromosomal abnormalities detected either by conventional cytogenetics (CC) or interphase fluorescence in situ hybridization (FISH) have emerged as important prognostic markers in patients with multiple myeloma (MM) and are used to stratify patients into standard-risk (SR) or high-risk (HR) disease. HR myeloma is associated with shorter remission and survival even with novel agents and autologous hematopoietic stem cell transplantation (auto-HCT). In this report, we describe the outcome of patients with myeloma who received auto-HCT at our institution between January 2008 and December 2009, and had CC and FISH analyses available before auto-HCT to identify HR or SR disease. Methods: Primary objective was to compare the response rate, transplant-related mortality (TRM), time to progression (TTP), progression-free survival (PFS) and overall survival (OS) between HR and SR myeloma. HR myeloma was defined as having deletion of chromosomal 13 or 13q, t(4;14), and del17p by CC; or detection of t(4;14), t(14;16), or del17p by FISH in the bone marrow plasma cells (Munshi, N et al. Blood 2011 117: 4696–4700). Normal or any other CC or FISH abnormalities were considered SR. Response was assessed according to international uniform response criteria for myeloma (BGM Durie et al. Leukemia 2006 20(10):1–7). Kaplan & Meier curves were generated to calculate progression free survival (PFS) and overall survival (OS). Results: Between Jan 2008- Dec 2009, we identified 205 patients, who received auto-HCT at our institution and had pre-transplant CC and FISH analyses available. Twenty-eight patients (14%) had HR while 177 (86%) had SR myeloma. Table 1 summarizes patient characteristics and outcomes for HR and SR patients. Nine HR (30%) and 29 (16%) SR patients had international staging system (ISS) stage III at diagnosis (p=0.04). Twenty-one HR patients (70%) and 91 SR patients (51%) received induction therapy with a bortezomib-based regimen (p=0.01). Thirteen (46%) HR patients and 62 (35%) SR patients received post auto-HCT maintenance therapy (p=0.24). Nineteen HR patients (69%) and 165 SR patients (92%) achieved a CR, VGPR or PR after auto-HCT (p=0.00001). The median follow up in HR and SR patients was 14.5 months (2–30) and 12 months (1–35), respectively. Twenty-two (79%) HR and 46 (25%) SR patients had progressed at last follow up (p=0.00001). Similarly, 12 (43%) HR and 12 (7%) SR patients had died at last follow up (p<0.0001). Median PFS was 9.1 months in HR while it was 30.8 months in SR patients (p=0.000001). Median OS in HR was 19 months while median OS has not yet been reached in SR patients (p=0.000001). In HR patients only the use of maintenance therapy post auto-HCT significantly improved PFS and OS (p=0.001 and p=0.0007, respectively). Conclusion: Patients with HR myeloma had significantly worse outcome than patients with SR disease, even with novel agents and auto-HCT. In HR patients, maintenance therapy was associated with longer PFS and OS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcome of Autologous Hematopoietic Stem Cell Transplantation in Relapsed and Refractory Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4626-4626
Author(s):  
Lauren Westfall Veltri ◽  
Denái R. Milton ◽  
Nina Shah ◽  
Krina Patel ◽  
Yago Nieto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Hemoglobin Level ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract Introduction: Despite the introduction of highly effective novel agents, the outcome of patients with relapsed and refractory multiple myeloma (RRMM) remains poor, particularly in those with disease refractory to both proteasome inhibitors (PI) and immunomodulatory agents (IMiDs). Limited available data suggests that autologous hematopoietic stem cell transplantation (auto-HCT) may be an effective therapy in this patient population. Methods: We retrospectively analyzed all patients with RRMM who underwent first auto-HCT at our center between March 2000 and October 2015. RRMM was defined as never achieving a response (stable disease [SD]) or having progressed while on therapy or within 60 days after discontinuation of therapy. Patients with disease refractory to at least one PI and at least one IMiD either in combination or administered separately were classified as double refractory (DR-MM). Results: 233 patients with RRMM were identified. Of these, 105 (45%) had DR-MM. The remaining 128 (55%) patients were classified as refractory (R)-MM and included all patients with RRMM but without history of being double refractory. Median age at auto-HCT was 59 years (DR-MM 60 vs. 56 years in R-MM, p=0.005). High-risk cytogenetics (IMWG criteria) were noticed in 67 of 140 (48%) patients (DR-MM, 35/89 [39%] vs. R-MM, 32/51 [63%], p=0.009). Median number of prior lines of therapy was 2 (range 1 - 7) (DR-MM, 2 (1 - 7) vs. R-MM, 1 (1 - 5), p<0.001). Eighty-two (35%) patients received induction with triplet chemotherapy regimens (DR-MM, n=55 [52%] vs. R-MM, n=27 [21%], p<0.001). Chemomobilization was used in 94 (40%) patients (DR-MM, n=54 [51%] vs. R-MM, n=40 [31%], p=0.002). Median time from diagnosis to auto-HCT was 9.4 months (DR-MM 12 vs. 8 months in R-MM, p<0.001). Conditioning regimen consisted of melphalan alone in 168 (72%) and various combinations with melphalan in 65 (28%) patients with no significant difference between DR-MM and R-MM. Maintenance therapy was used in 113 (49%) patients (DR-MM, n=63 [60%] vs. R-MM, n=50 [39%], p=0.001). With a median follow up of 36 months post auto-HCT, at least partial response was seen in 188 (81%) patients (DR-MM, n=83 [79%]; R-MM, n=105 [82%], p=0.50). Near complete remission or better was seen in 52 (22%) patients (DR-MM, n=25 (24%); R-MM, n=27 (21%), p=0.64). The cumulative incidence of non-relapse mortality (NRM) at day 100 and 6 months was 1% and 2% (DR-MM, 0% and 1%; R-MM 2% each at day 100 and 6 months, p=0.56), respectively. The median progression-free survival (PFS) was 17.6 months (14.4 months in the DR-MM and 18.2 months in the R-MM, p=0.40) (Figure 1). Median overall survival (OS) was 48 months (39 months in DR-MM and 57 months in R-MM, p=0.27) (Figure 2). When accounting for other significant measures (i.e., hemoglobin level and β2 microglobulin), having high-risk chromosomal abnormalities was significantly associated with worse PFS (p=0.006) while worsening of PFS for patients with ISS stage II or III disease approached significance (p=0.06). A significant association between OS and hemoglobin level, β2 microglobulin, high risk cytogenetics, ISS stage, and induction treatment was observed, however, none of these measures remained significant in the multivariable model. Conclusions: Our findings highlight that auto-HCT is an effective and safe therapy in patients with RRMM including those who are refractory to an IMiD and PI Figure 1 Progression Free Survival Figure 2. Overall Survival Figure 1. Progression Free Survival Figure 2. Overall Survival Figure 2 Figure 2. Disclosures Ciurea: Cyto-Sen Therapeutics: Equity Ownership; Spectrum Pharmaceuticals: Other: Advisory Board.

scholarly journals Durable Remission and Survival in Relapsed/Refractory Multiple Myeloma after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5884-5884 ◽  
Author(s):  
A. Megan Cornelison ◽  
Rima M Saliba ◽  
Sairah Ahmed ◽  
Yago Nieto ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Durable Remission

Abstract Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the setting of refractory multiple myeloma (MM) is still controversial. Although potentially curative in a subset of pts, concerns regarding treatment related mortality (TRM) and graft vs. host disease (GVHD) preclude its universal use. In this study, we evaluated the role of allo-HSCT for pts with relapsed MM. Methods: 110 consecutive pts with relapsed MM underwent allo-HSCT at our institution between 2000 and 2014. The primary objective was to assess progression-free (PFS) and overall survival (OS). Results: Median age at allo-HSCT was 54 (range, 32-71) years and median time from diagnosis to allo-HSCT was 35.7 (range, 8.6 to 228.8) months. Fifty-two (47%) and 49 (45%) pts had standard-risk (SR) and high-risk (HR) cytogenetics at the time of allo-HSCT, respectively. Pts received a median of 5 (range, 1-9) prior chemotherapy regimens and 99 (90%) pts had at least 1 (range, 0-3) prior auto-HSCTs. One hundred one (92%) pts received either a proteasome inhibitor (PI) or an immunomodulatory drug (IMiD) prior to allo-HSCT, with 65 (59%) receiving both. Sixty eight (62%) received allo-HSCT from matched related, 34 (31%) from matched unrelated, 5 (4%) from cord blood, and 3 (3%) from mismatched donors. Preparative regimen was fludarabine/melphalan-based in 88 (80%) and fludarabine/busulfan-based in 16 (15%) pts. Median time to neutrophil and platelet engraftment was 12 (range, 8-30) and 13 (range, 0-81) days, respectively. Ten pts died of non-relapse causes within 100 days (100-day TRM: 9%) and 21 (19%) within 1 year. Grade 1-4 acute GVHD was seen in 50 (45%) and cGVHD in 35 (32%) pts, respectively. Eighteen (16%) achieved a CR, 26 (23%) a VGPR and 38 (34%) achieved a PR, with an overall response rate of 73%. With a median follow up of 41.9 months (range, 6.4 to 172.9) in surviving pts, 1- and 2-year PFS were 23% and 15%, respectively (Fig 1). One and 2-year OS were 50% and 32%, respectively (Fig 2). HR cytogenetics at allo-HSCT were associated with a significantly shorter 2-year PFS (6% for HR vs. 23% for SR; p=0.007) and OS (p=0.01). A response <PR after allo-HSCT was also associated with significantly shorter 2-year PFS (p<0.001) and OS (p<0.001). Conclusions: Allo-HSCT is associated with durable remission and survival in approximately 15% of heavily pretreated pts with relapsed/refractory MM. Novel, more effective approaches are needed for patients with HR cytogenetic abnormalities. Figure 1 Progression-Free Survival Figure 1. Progression-Free Survival Figure 2 Overall Survival Figure 2. Overall Survival Disclosures No relevant conflicts of interest to declare.

Upfront Autologous Stem Cell Transplantation Overcome the poor Prognosis of Non-Germinal Center Subtype of diffuse Large B-Cell Lymphoma in Patients with Advanced Stage and Elevated Serum Lactate Dehydrogenase

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3998-3998
Author(s):  
Yu Ri Kim ◽  
Soo-Jeong Kim ◽  
June-Won Cheong ◽  
Yundeok Kim ◽  
Ji Eun Jang ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Progression Free Survival ◽  
Molecular Classification ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract Introduction: The role of frontline autologous hematopoietic stem cell transplantation (ASCT) high-risk diffuse large B-cell lymphoma (DLBCL) is still controversial. We investigated the role of upfront ASCT as consolidation for high-risk DLBCL treated with rituximab containing chemotherapy according to molecular classification. Methods: A total of 195 newly diagnosed DLBCL patients with advanced stage and elevated serum lactate dehydrogenase from three centers were retrospectively analyzed. All patients achieved more than partial response (PR) after completing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) with rituximab (R-CHOP). Molecular classification was performed according to Han's algorithm. Results: One hundred fifty (76.9%) patients achieved complete response (CR) and 45 (23.1%) patients PR after frontline R-CHOP chemotherapy. Among these patients, sixty six (33.8%) patients were received ASCT. The 2-year overall survival (OS) was 82.9% and the 2-year progression-free survival (PFS) was 72.1%. Seven (10.6%) patients were relapsed after ASCT while 29 (22.5%) patients were relapsed in non-transplant patients. Patients who treated with ASCT showed superior OS and PFS (P=0.036, P=0.005). According to final response, ASCT showed superior OS and PFS in PR patients (P = 0.024, P = 0.009) while it did not in CR patients. Among the 128 patients that underwent immunohistochemistry for molecular classification, 36 patients (28.1%) were classified to GCB type, 92 (72.9%) patients were non-GCB type. Twenty five (27.1%) non-GCB patients received ASCT showed significant survival benefit for OS and PFS (P=0.032, P=0.011) while GCB patients did not show the survival difference according to ASCT (Figure 1). In non-GCB DLBCL, ASCT was related with superior PFS both interim and final PR status (P = 0.006, P=0.028). There was no difference for OS and PFS between GCB and non-GCB type in ASCT patients while GCB patients showed superior OS and PFS in non-transplant patients (P = 0.048, P=0.009). Conclusions: ASCT as consolidation improved OS and PFS in high risk DLBCL patients following R-CHOP chemotherapy. Especially, it could overcome the poor prognosis of non-GCB type DLBCL. Upfront ASCT could be considered effective treatment options for non-GCB type high risk DLBCL. Figure 1. Overall survival and progression free survival according to autologous hematopoietic stem cell transplantation in non-GCB type DLBCL. Figure 1. Overall survival and progression free survival according to autologous hematopoietic stem cell transplantation in non-GCB type DLBCL. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia

Blood ◽  
2005 ◽  
Vol 106 (13) ◽  
pp. 4389-4396 ◽  
Author(s):  
John G. Gribben ◽  
David Zahrieh ◽  
Katherine Stephans ◽  
Lini Bartlett-Pandite ◽  
Edwin P. Alyea ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Matched Sibling

We report here on the long-term follow-up on 162 patients with high-risk chronic lymphocytic leukemia (CLL) who have undergone hematopoietic stem cell transplantation (SCT) at a single center from 1989 to 1999. Twenty-five patients with human leukocyte antigen (HLA)-matched sibling donors underwent T-cell-depleted allogeneic SCT, and 137 patients without HLA-matched sibling donors underwent autologous SCT. The 100-day mortality was 4% for both groups, but later morbidity and mortality were negatively affected on outcome. Progression-free survival was significantly longer following autologous than allogeneic SCT, but there was no difference in overall survival and no difference in the cumulative incidence of disease recurrence or deaths without recurrence between the 2 groups. At a median follow-up of 6.5 years there is no evidence of a plateau of progression-free survival. The majority of patients treated with donor lymphocyte infusions after relapse responded, demonstrating a significant graft-versus-leukemia effect in CLL. From these findings we have altered our approach for patients with high-risk CLL and are currently exploring the role of related and unrelated allogeneic SCT following reduced-intensity conditioning regimens.

scholarly journals Early Intensive Therapy in Multiple Myeloma Using Tandem Transplantation with Novel Conditioning and Two Years Maintenance: A Single Institution Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2152-2152
Author(s):  
Kalyan Nadiminti ◽  
Christopher Strouse ◽  
Praveen Vikas ◽  
Lindsay Dozeman ◽  
Allyson Schultz ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Maintenance Phase ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Regimen Change ◽  
Preparative Regimen

Abstract Introduction The role of early intensive treatment of multiple myeloma, including tandem autologous stem cell transplantation( ASCT) with bortezomib, thalidomide, dexamethasone( VDT) and melphalan 200mg/m2 as a preparative regimen, followed by 2 years of combination agent maintenance therapy, is being studied. We sought to analyze a cohort of patients who received early intensive treatment at the University of Iowa between 2012 and 2016. Patients and Methods All consecutive patients who received early( < 12 months since diagnosis) tandem ASCT and have completed at least 2 years of maintenance therapy between 2012 and 2016 were included for analysis. Planned maintenance therapy consisted of a combination of VDT in 28 day cycles for year 1 and bortezomib, cyclophosphamide and dexamethasone(VCD) in 28 day cycles for year 2. Alternate regimen were used in case of toxicities. The patients were considered to have high risk cytogenetics if they had 17p deletion, t(14;16), amp 1q, or t(4;14) by FISH. Event-free (EFS) and overall survival (OS) probabilities were estimated and plotted using the Kaplan-Meier method. For EFS, time was calculated from date of first transplant to relapse or death due to any cause. Treatment-related mortality was defined as death during transplant phase or maintenance phase due to causes other than disease relapse.The effect of clinical characteristics on outcomes was evaluated using Cox regression models. Estimated effects of predictors are reported as hazard ratios (HR) along with 95% confidence intervals. All statistical testing was two-sided and assessed for significance at the 5% level using SAS v9.4 (SAS Institute, Cary, NC). Responses were measured using IMWG consensus criteria. Results A total of 135 patients met the criteria for inclusion. Key patient characteristics are shown in table 1. The median age at first transplant was 58 years. HCT-CI was high in 68% of patients. 36% of the patients were ISS stage III, and high risk cytogenetics were present in 56%. Preparative regimen was VTD-Mel 200 in 88.9% of patients. Following the first transplant, 59% of patients had achieved CR, and following the second transplant 94.4% of patients achieved CR. At the time of median follow up, 27.4% of patients had died. The cause of death was infection (25%), organ failure (11%), relapsing myeloma (28%) or other (36%). Univariable analysis identified a statistically significant association only for age with risk of progression or death. Kaplan-Meier curves for progression free survival and overall survival in patients with high risk or low risk cytogenetics are shown in Figures 1 and 2 respectively. The hazard ratio for progression free survival and overall survival in patients with high risk vs low risk cytogenetics was 0.86 (95% confidence interval 0.45 - 1.64, p=0.65), and 0.88 (95% confidence interval 0.45 - 1.73, p=0.71), respectively. The 3 year EFS and OS of patients who received early tandem ASCT followed by 2 years of maintenance were 73% and 72%, respectively. Following the 2nd autologous transplant, 128 of 135( 94%) patients were started on maintenance therapy. VTD ( 74%) and VRD (6%) were the most common regimens used. Fifty six patients completed maintenance therapy for 1 year without regimen change, and 60 required regimen change due to toxicities. VRD (20), VPomD (9) and VRMp (8) were the most commonly used alternative regimens in the case of toxicities. Following year 1 of maintenance, 96 patients (75%) started a second year of maintenance. VCD (30%) or RD (23%) were the most common regimens. 63(43%) patients completed 2 years of combination maintenance therapy. Grade III-V non-hematologic toxicities during the combined maintenance phase were infection (56%) and peripheral neuropathy (23%) and hematologic toxicities were thrombocytopenia (13%), neutropenia (12%) and anemia (8%). Conclusion According to our results, patients with high risk cytogenetics did not have an inferior PFS and OS. These results suggest that in newly diagnosed MM patients, upfront treatment using novel conditioning regimen and tandem ASCT followed by intensive maintenance therapy can result in a very high CR rates, particularly in patients with high risk cytogenetics. Infections and peripheral neuropathies were the most common non-hematologic toxicities during maintenance. Longer follow up will determine further impact of maintenance therapy. Disclosures No relevant conflicts of interest to declare.

Outcome Depend On Age But Not Comorbidity Score, In Patients treated With Fludarabine and Busulfan (FB4) As Conditioning Regimen In Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4533-4533
Author(s):  
Javier Nunez ◽  
Arancha Bermudez ◽  
Lucrecia Yanez ◽  
Guillermo Martin ◽  
Andres Insunza ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Free Survival ◽  
Myeloid Neoplasms ◽  
High Risk Disease ◽  
Comorbidity Index

Introduction The best conditioning regimen in allogeneic stem cell transplantation (SCT) for myeloid malignancies is unknown. In the last decade, conditioning regimens based on busulfan (BU) and fludarabine (FLU) have shown a good security profile with low early toxicity and mortality but long term follow up is needed to confirm the efficacy in the disease control. Objective To analyze retrospectively the efficacy (overall survival OS, progression free survival PFS) of the conditioning regimen with FLU (40mgr/m2/4 days) and BU (3,2 mgr/kg once daily/4 days) in adult patients with myeloid neoplasms after SCT. Outcome was assessed considering age, comorbidity, disease, and donor. Patients and transplant characteristics Between 2006 and 2012, 90 patients (40 males, 50 females) underwent SCT conditioned with FB4 in our center. The median age of patients was 50 (24-74) years and 34 patients (37%) were older than 55 years. The diagnoses were 65 AML (11 secondary AML and 19 with adverse cytogenetic), 19 MDS (11 with IPSS high/intermediate 2) and 6 MPD (3 CML, 3 myelofibrosis). At time of SCT, 52 patients (80%) with AML were in first CR. High risk disease (secondary AML or with adverse cytogenetic and MDS with high/intermediate IPSS) were considered in 41 patients (45%). The HCT comorbidity index (Sorror) was low, intermediate or high in 20 (22%), 31 (34%) and 39 (43%) patients, respectively. Donor type was matched related in 42 patients (47%), matched unrelated in 30 patients (33%) and mismatched unrelated in 18 patients (20%). Stem cell source were bone marrow in 81 cases (90%). GvHD prophylaxis was done with calcineurin inhibitor associated with short course of methotrexatre or mycophenolate in all patients and Thymoglobulin was administered in 8 patients (9%). Results All patients but one engrafted. The median time to recovery >500 ANC/uL and >50000 platelets/uL was 16 days (range, 9-28) and 16 days (range, 11-455) respectively. Donor complete chimerism was achieved during first or second month in 90% cases. The incidence of acute GVHD grade II-IV and III-IV was 45% and 12% respectively. Chronic GvHD was diagnosed in 60 patients (68%) (26 mild, 18 moderate and 16 severe) and 22 patients (36%) had pulmonary affectation. Transplant related mortality at 100 days and 1 year was 5.5% and 15%. With a median follow up of 26 months (IQL 12-45), the estimated overall survival (OS) was 64% and progression free survival (PFS) was 61%. To be more than 55 years at time of SCT had a negative impact on survival (estimated OS at 40 months: 42% vs 75%, p=0.005). Neither HCT comorbidity index nor disease type had a significant influence on estimated OS at 40 months (70%, 62% and 58% in low, intermediate and high risk) and (64% in AML and 51% in MDS) respectively. However considering the group of high risk disease had worse OS (53% vs 78%, p=0.07). Although there was no significant difference, the OS in mismatched unrelated SCT was worse than matched unrelated and related SCT (40%, 63 % and 71%). Conclusion Conditioning regimen with fludarabine and busulfan (FB4) offers a good effectiveness in patients with myeloid neoplasms and allow the use of myeloablative regimen in patients with high risk disease and significant comorbidities. Only the age at time of SCT had a statically significant impact on overall survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Induction Treatment and Feasibility of Allogeneic Hematopoietic Stem Cell Transplantation in Young Patients (<65 years) with High-Risk Cytogenetic and Secondary Acute Myeloid Leukemia (AML): A Single Center Experience in Argentina with CLAG-M and 7+3

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5132-5132
Author(s):  
Maria Lucia Fuente ◽  
Maria Del Rosario Custidiano ◽  
Santiago Cranco ◽  
Laura Korin ◽  
Paola Ochoa ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Median Time ◽  
Induction Treatment ◽  
Hematopoietic Stem ◽  
Free Survival

BACKGROUND Patients with adverse cytogenetic or secondary AML (s-AML) have significantly worse outcomes and lower survival rates. In this high risk subgroup of patients, early consolidation with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) can improve results, especially in those who achieve negative measurable residual disease (MRD-). More effective treatments than standard 7+3 are needed. CLAG-M is a salvage regimen that has demonstrated high response rates with good tolerance, and seems to be promising in the upfront setting. AIMS To estimate CR and MRD- rates, overall survival (OS) and event free survival (EFS) in transplant eligible patients with high risk AML treated in our center.To compare CR rate and transplant feasibility in CR1 with 7+3 vs. CLAG-M as induction treatment in s-AML. PATIENTS AND METHODS We analyzed adult patients (18-65 years old) with high risk AML (defined by adverse cytogenetic according to ELN2017 or s-AML) who were treated in our institution between 2010 and 2018. All patients were transplant eligible and had an available donor. Clinical information was collected from medical records. We evaluated CR1 and MRD- rates, EFS and OS. We also compared CR rates and HSCT feasibility in s-AML after treatment induction with CLAG-M and 7+3. The survival analysis was estimated with Kaplan-Meier method and the comparison between variables was performed through log-rank test. RESULTS Twenty-one patients were included (13 s-AML and 8 with adverse cytogenetic). The median age at diagnosis was 54 years (21-64); 13 female/8 male. Out of 21 patients, 14 received 7+3 induction and 7 CLAG-M. The median follow-up time was 11 months (0.9-90.8), median EFS and OS for the whole group was 1.05 and 13.5 months, respectively. Two-year OS was 35%. CR1 was achieved in sixteen patients (76%), 10 of them MRD-. The median time to CR1 was 33 days, the median OS of these patients was 26.7 months (figure 1). Eleven patients (52%) were refractory to first induction, 10/14 in the 7+3 subgroup, and only 1/7 patients treated with CLAG-M. Six of them converted to CR after reinduction (5 with CLAG-M). Fourteen (67%) underwent HSCT in CR1. The median time to HSCT consolidation was 106 days. The median relapse free survival in transplanted patients has not been reached (Table 1). Considering only s-AML, 6 patients received 7+3 and 7 CLAG-M. Median age in 7+3 subgroup was 41 vs. 57 years in CLAG-M. The median OS was 13.5 months. In the 7+3 cohort, only 1 achieved CR (16%); the other five received reinduction with CLAG-M, and 4 converted to CR1. The median time to CR1, EFS and OS were 82 days, 1 month and 26 months respectively. In contrast, 4 of the 7 patients (57%) that received CLAG-M achieved CR1, but only 1 of the 3 that were refractory could convert to CR. The median time to CR1 in patients treated with CLAG-M was 27 days, median EFS 7.5 months and median OS has not been reached (Figure 2). There were no statistically significant differences between the two treatment groups. Eight patients (62%) could be bridged to HSCT, 4 of each subgroup (Table 2). CONCLUSIONS Our results in this real life small cohort of high risk AML were similar to historical controls. In the s-AML subgroup, differences between 7+3 and CLAG-M were not statistically significant probably due to the low number of patients analyzed. However, patients who received CLAG-M required less cycles of treatment to achieved CR1, allowing HSCT rapidly in this selected population. Since most of the refractory patients to 7+3 responded to reinduction with CLAG-M, both groups had similar transplant rates. According to our experience CLAG-M might be an attractive treatment option with high CR rates and acceptable safety profile. In this high risk AML population, two thirds of the patients were effectively "bridged" to HSCT with a 2-year OS rate of 35%. Disclosures No relevant conflicts of interest to declare.

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