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 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.

scholarly journals Day 100 Peripheral Blood Absolute Lymphocyte/Monocyte Ratio and Survival in Classical Hodgkin's Lymphoma Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Luis F. Porrata ◽  
David J. Inwards ◽  
Stephen M. Ansell ◽  
Ivana N. Micallef ◽  
Patrick B. Johnston ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Clinical Outcomes ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival

Day 100 prognostic factors of postautologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to predict clinical outcome in classical Hodgkin lymphoma (cHL) patients have not been evaluated. Thus, we studied if the day 100 peripheral blood absolute lymphocyte/monocyte ratio (Day 100 ALC/AMC) affects clinical outcomes by landmark analysis from day 100 post-APBHSCT. Only cHL patients achieving a complete remission at day 100 post-APBHSCT were studied. From 2000 to 2010, 131 cHL consecutive patients qualified for the study. The median followup from day 100 was 4.1 years (range: 0.2–12.3 years). Patients with a Day 100 ALC/AMC ≥ 1.3 experienced superior overall survival (OS) and progression-free survival (PFS) compared with Day 100 ALC/AMC < 1.3 (from day 100: OS, median not reached versus 2.8 years; 5 years OS rates of 93% (95% CI, 83%–97%) versus 35% (95% CI, 19%–51%), resp., P<0.0001; from day 100: PFS, median not reached versus 1.2 years; 5 years PFS rates of 79% (95% CI, 69%–86%) versus 27% (95% CI, 14%–45%), resp., P<0.0001). Day ALC/AMC ratio was an independent predictor for OS and PFS. Thus, Day 100 ALC/AMC ratio is a simple biomarker that can help to assess clinical outcomes from day 100 post-APBHSCT in cHL patients.

scholarly journals Early Organ Toxicity Following Allogeneic Hematopoietic Stem Cell Transplantation Differs By Conditioning Regimen

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4489-4489
Author(s):  
Joshua A Fein ◽  
Avichai Shimoni ◽  
Ivetta Danylesko ◽  
Noga Shem-Tov ◽  
Ronit Yerushalmi ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Patient Characteristics ◽  
Hematopoietic Stem ◽  
Organ Toxicity ◽  
Conditioning Regimens

Background: In recipients of allogeneic hematopoietic stem cell transplantation (HSCT), organ toxicity is a barrier to administering high-intensity conditioning regimens. We hypothesized that determinants of acute organ toxicity are specific to individual conditioning regimens. We sought to characterize toxicities across common transplantation regimens, evaluate their prognostic implication, and derive predictors of severe toxicity at the regimen level. Methods: This retrospective study included adults undergoing first allogeneic HSCT at a single center between the years of 2001 and 2014 (median: 2010). Patients received grafts from matched sibling or unrelated donors and were conditioned with any of the following regimens: Cyclophosphamide + TBI (Cy/TBI), Busulfan + Cyclophosphamide (Bu/Cy), Fludarabine + 12.8 mg Busulfan (Flu/Bu4), Fludarabine + 6.4 mg Busulfan (Flu/Bu2), Fludarabine + 36-42 gr/m2 Treosulfan (Flu/Treo), and Fludarabine + 100-140 mg/m2 Melphalan (Flu/Mel). Toxicities were defined by the KDIGO scale for acute kidney injury (AKI) and by the CTCAE v. 5.0 for increases in total bilirubin, AST, ALT, and alkaline phosphatase (Alk. Phos.) The incidence of toxicities from the start of conditioning through 30 days post-transplantation was tabulated by regimen. Risk factors for severe organ toxicity were assessed within each regimen cohort using multivariable logistic regressions. Results: In a cohort of 707 patients, the median age was 52 years. The main indications for transplantation were acute leukemia (57%), myelodysplastic syndrome (13%), and aggressive lymphoma (9%). Graft-versus-host-disease prophylaxis included methotrexate in 80% of patients, and 56% received anti-thymocyte globulin (ATG). The most common regimens were Flu/Treo (n = 160) and Bu/Cy (n = 141). As expected, patient characteristics varied between regimens. The incidence of AKI and increased serum bilirubin in each regimen is shown in Figure 1A and 1B, respectively. Sinusoidal-obstructive syndrome (6% overall) accounted for only 17% of gr. ≥ 3 bilirubinemia in the entire cohort. Elevations in AST, ALT, and Alk. Phos of gr. ≥ 3 were not common (<8%). In multivariable logistic regression, AKI gr. ≥ 2, increased bilirubin gr. ≥ 3, AST gr. ≥ 3, and Alk. Phos. gr. ≥ 2 were associated with increased 100-day mortality (p < 0.05). Acute severe organ toxicity (ASOT) was defined as the occurrence of any of these toxicities. ASOT had an odds ratio (OR) of 3.4 (95% CI: 2.2-5.3) for 100-day mortality. Within each regimen, we studied the relationship between ASOT and transplantation/patient characteristics (Figure 1C). Elevations in baseline bilirubin were predictive of ASOT in Cy/TBI (OR: 1.68 [1.19-2.37]), while increasing creatinine was predictive in patients conditioned with Flu/Mel (OR: 1.43 [1.09-1.88]). High-risk disease (DRI) was associated with increased risk in patients receiving Flu/Bu4 (1.26 [1.01-1.58]). In patients treated with Bu/Cy, administration of ATG increased the risk of ASOT (1.31 [1.11-1.55]). Conclusion: Allogeneic stem cell transplantation recipients are at high risk for acute organ damage. We describe patterns of renal and liver toxicity across several regimens. Determinants of acute severe organ toxicity, defined as those associated with short-term mortality, are regimen dependent. Our findings suggest that these factors should be considered when selecting the preparative regimen. While requiring validation, the newly-defined composite endpoint of acute severe organ toxicity (ASOT) may be valuable in studying transplantation strategies. Figure 1 Disclosures No relevant conflicts of interest to declare.

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