Fludarabine and Melphalan Conditioning Regimen in Young Patients with Acute Myeloid Leukemia in CR1 Undergoing a Matched Related Allogeneic Stem Cell Transplant: A Single Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5049-5049 ◽  
Author(s):  
Mammen Chandy ◽  
Vikram Mathews ◽  
T. Rajasekar ◽  
Kavitha M. Lakshmi ◽  
Auro Viswabandya ◽  
...  
Keyword(s):  
Young Adults ◽  
Clinical Outcomes ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Young Patients ◽  
Cell Transplant ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier

Abstract Allogeneic SCT remains the most effective anti-leukemic therapy. However, due to the associated TRM with conventional myeloablative regimens, this has often not translated to a significant improvement in EFS or OS. Since October 2005, at our center, we offered a RIC regimen consisting of fludarabine 30mg/m2 x 5days followed by one dose of melphalan 140mg/m2 for young adults with AML in CR1 after induction chemotherapy. GVHD prophylaxis consisted of cyclosporine with a low dose short course methotrexate. The graft source was a PBSC harvest. The clinical outcomes were compared with a historical control who received a conventional Bu/Cy regimen. Since October 1992, 55 of patients with AML in CR1 (constituted 47% of all AML transplants done at our center) underwent a matched related allogeneic SCT. Among these 11 received a Flu/Mel conditioning regimen while 41 received a conventional Bu/Cy conditioning regimen (3 patients excluded from analysis since they received other conditioning regimens), the clinical outcomes of these two groups were compared. All, except for one donor (one antigen mismatch) in the Bu/Cy group, were complete 6/6 HLA identical related donors. The age (mean±SD) of patients in the Flu/Mel and the Bu/Cy group was 39±14 and 27±11 respectively. The baseline characteristics of these two groups were comparable for sex, donor age, female to male transplants, AML subtypes and requirement of two course of chemotherapy to achieve CR1. Four (36.4%) of patients among the Flu/Mel group and 28 (68.3%) in the Bu/Cy group received one or two cycles of consolidation chemotherapy prior to SCT. All patients in the Flu/Mel group received a PBSC graft while only 26 (41%) among the Bu/Cy group received a PBSC graft (P=0.05). One patient in the Bu/Cy group failed to engraft. All other cases engrafted. All 11 (100%) cases in the Flu/Mel group had a complete donor chimerism documented on day 30. Prophylactic donor lymphocyte infusion was not administered for any patient. There were no treatment related deaths in the Flu/Mel group up to day 100. One patient died on day 299 following pulmonary GVHD and septicemia. In comparison, the day 100 TRM was 8 (19.5%), going up to a one year all cause mortality of 21 (51%) in the Bu/Cy group. Acute GVHD grade 2–4 occurred in 5 (45.5%) and in 14 (34.1%) among patients conditioned with Flu/Mel and Bu/Cy, respectively. Chronic GVHD occurred in 4 (36.4%) of patients conditioned with Flu/Mel and was similar to the incidence seen in the Bu/Cy group. During the period of follow up none of the patients in the Flu/Mel group have relapsed while 11 (26.8%) patients had relapsed in the Bu/Cy group. The 2 year Kaplan-Meier estimate of EFS and OS for the Flu/Mel and Bu/Cy group (mean follow up 19 and 71 months, respectively) was 85.71±13.23 vs. 43.19±7.82 (P=0.0176) and 85.71±13.23 vs. 45.59±7.86 (P=0.027) respectively. A conditioning regimen of fludarabine and melphalan in young adults with AML in CR1 is associated with a low TRM with a potential to translate into improved EFS and OS. Figure 1: Kaplan-Meier estimate of Event Free Survival among patients who received Flu/Mel conditioning (n=11) versus those that received a Bu/Cy conditioning regimen (n=41) Figure 1:. Kaplan-Meier estimate of Event Free Survival among patients who received Flu/Mel conditioning (n=11) versus those that received a Bu/Cy conditioning regimen (n=41)

High Dose BCNU/Melphalan Preparative Regimen Doubles Event Free Survival of Myeloma Patients Undergoing Autologous Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2012-2012
Author(s):  
Cristina Gasparetto ◽  
Wendi A. Bacon ◽  
Phuong Doan ◽  
David A. Rizzieri ◽  
Mitchell E. Horwitz ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Conditioning Regimen ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Event Free Survival ◽  
Free Survival ◽  
Preparative Regimen ◽  
Related Mortality

Abstract Abstract 2012 High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) remains a valid treatment option for patients with multiple myeloma (MM). HDC has improved response rate, event-free survival (EFS) and treatment free interval for patients with MM when compared with conventional chemotherapy. To date, Melphalan 200 mg/m2 (HDM) remains the standard ASCT preparative regimen as no other regimens have demonstrated improved outcomes with acceptable toxicity. Nevertheless, relapse remains inevitable with this approach prompting continued search for better therapies. To overcome resistance and early relapse we used a more aggressive alkylator based conditioning regimen. Here we summarize a retrospective study of the long-term follow-up of newly diagnosed MM patients treated with the preparative regimen Carmustine, 500 mg/m2 and Melphalan, 200 mg/m2 (BCNU/HDM) followed by ASCT versus a subsequent group of patients treated with HDM alone and ASCT. Methods: Between November of 1997 and December of 2008, 207 patients with MM underwent HDC followed by ASCT at our Institution, using either BCNU/HDM (n = 104, treated between 1997–2002) or HDM (n = 103, treated between 2002–2008) as the preparative regimen. Presenting patient characteristics were similar (age, gender, MM type, hemoglobin, creatinine, calcium, plasma cell infiltration, Durie-Salmon stage, and ISS stage). Patients treated with BCNU/HDM were diagnosed preceding the introduction of novel anti-MM agents such as thalidomide, lenalidomide, and bortezomib and thus did not receive these as induction therapy, while HDM patients received various combinations of novel agents as induction therapy. Results: With a median follow-up for surviving patients of 96 and 34 months for the BCNU/HDM and HDM cohorts, respectively, the event-free survival (EFS) was significantly increased with the BCNU/HDM conditioning regimen (41.7 months) as compared with the HDM regimen (21.6 months, p = 0.013) (Figure 1). Median overall survival (OS) was 83.1 months with BCNU/HDM vs. 68.2 months with HDM (p = 0.359 at current follow-up) with 34% of BCNU/HDM patients alive at >10 years (Figure 2). In the BCNU/HDM group, 47/104 patients achieved ≥VGPR and this subgroup had a median OS of 103 months. Nineteen patients in the BCNU/HDM group are ≥7 years from ASCT and 18 (17%) have never required treatment for progressive disease. Engraftment and transplant-related mortality were similar in both groups (3% TRM in the BCNU/HDM and 4% TRM in the HDM arm). The BCNU/HDM group had a higher incidence of pneumonitis (50%) vs. the HDM group (15%) but this was managed with short courses of steroids and was never fatal. Focusing on the subgroup of patients who proceeded to transplant immediately after only 1 induction course, the median OS was 103 months for the BCNU (80 patients) containing arm versus 69 months for the HDM (71 patients) arm (p=0.085), suggesting a clear trend further favoring this dose dense approach. Conclusions: EFS was superior with the BCNU/HDM regimen compared with HDM and a subgroup of patients treated with BCNU/HDM have achieved EFS >7 years without any additional therapy. Engraftment and treatment related mortality were similar in both groups despite advances in supportive care for the HDM group. Our findings suggest that BCNU/HDM should be compared in a randomized prospective fashion to HDM as an ASCT preparative regimen following optimal induction therapy with novel agents to determine whether this will lead to further improvements in EFS and OS following ASCT. Disclosures: No relevant conflicts of interest to declare.

PET-CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis in 173 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1772-1772
Author(s):  
Santiago Pavlovsky ◽  
Astrid Pavlovsky ◽  
Isolda Fernandez ◽  
Miguel Pavlovsky ◽  
Virginia Prates ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Progressive Disease ◽  
Cell Transplant ◽  
Advanced Stage ◽  
Event Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Pet Ct

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.

Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Survival for Patients with Chronic Myelomonocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4347-4347 ◽  
Author(s):  
Piyanuch Kongtim ◽  
Uday R. Popat ◽  
Antonio M. Jimenez ◽  
Sameh Gabella ◽  
Riad O. El Fakih ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Hypomethylating Agents ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Unrelated Donors ◽  
Conditioning Regimens

Abstract Introduction Allogeneic hematopoietic stem cell transplant (allo-SCT) is the only curative treatment modality for patients with CMML. Here we retrospectively reviewed the data for patients with CMML who received an all-SCT at our institution to identify factors associated with improved survival and determine whether treatment with hypomethylating agents (HMA) before transplant improves survival for these patients. Methods All 83 patients 18 years of age or older with a diagnosis of CMML confirmed at The University of Texas MD Anderson Cancer Center who underwent allo-SCT between April 1991 and December 2013 were identified through review of the institutionÕs medical records and included in this analysis. Forty, 7, and 36 patients had CMML-1, CMML-2 and CMML that had progressed to AML (CMML/AML) respectively. The median age was 57 years. CMML specific cytogenetic risk at diagnosis (Such E, hematologica, 2011) was good, intermediate, and high risk in 46, 19, and 18 patients respectively. Seventy-eight patients received induction treatment before transplant, 37 receiving HMA (either 5-azacytidine or decitabine) for at least 3 courses and 41 receiving 1-2 courses of cytotoxic chemotherapy. Among the patients who received induction therapy, 15 patients in HMA group and 9 patients in convention chemotherapy group achieved a complete remission before transplant. Thirty, 47 and 6 patients received transplants from matched related donors (MRD), matched unrelated donors (MUD), and mismatched related or unrelated donors (MMD), respectively. The sources of hematopoietic stem cells were peripheral blood for 48 patients (57.8%) and bone marrow for 35 patients (42.2%). Conditioning regimens varied; most patients received either fludarabine in combination with busulfan or fludarabine combined with melphalan. Sixty-four patients received myeloablative and 19 patients received reduced intensity conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Patient and transplant characteristics did not significantly differ between the patients treated with HMA and the patients treated with conventional chemotherapy or given supportive care alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), Treatment related mortality (TRM), relapse incidence through last follow-up and incidences of acute GVHD and chronic GVHD. All of these outcomes were measured from the time of allo-SCT. Results Median follow up duration for 29 survivors was 48 months. Seventy-five patients engrafted (90.4%) with median time to neutrophil and platelet engraftment of 13 and 15 days respectively. Patients treated with a HMA had a significantly lower cumulative incidence (CI) of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplantdid not significantly differ between the groups (27% and 30%, respectively; p=0.84). Acute GVHD all grades and grade 2-4 were seen in 28.2% versus 35.8% (p=0.05) and 12.8% versus 11.3% (p=0.72) in patients who received a HMA compared to those who treated with other agents respectively. CI of chronic GVHD was 35% in patients treated with a HMA versus 19.2% in those treated with other agents (p=0.36) while CI of chronic extensive GVHD was seen in only 26.7% versus 19.2% respectively (p=0.64). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a HMA (43%) than in those who received other treatments (27%; p=0.04) (Figure 1). However, therapy with HMA before transplant did not significantly influence the 3-year OS rate (45% in those treated with HMA and 39% in those treated with other agents; p=0.22). The independent prognostic factors for PFS were a blast count of < 5% before transplant (HR 0.36, 95%CI 0.14-0.78), treatment with a HMA (HR 0.44, 95% CI 0.23-0.86), a transplant from an MRD (HR 0.41, 95% CI 0.22-0.94), development of grade 2-4 acute GVHD (HR 2.7, 95% CI 1.27-5.77), and development of chronic GVHD (HR 0.15, 95% CI 0.05-0.45). Conclusion We conclude that treatment with hypomethylating agents before allo-SCT may improve survival in patients with CMML. Figure 1. Progression free survival Figure 1. Progression free survival Disclosures Alousi: Therakos, Inc: Research Funding. Andersson:Otsuka Research and Development, Inc.: Consultancy.

Treatment of 11q23/MLL + AML with Gemtuzumab Ozogamicin: Results from the Randomized Phase III Children's Oncology Group Trial AAML0531

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 799-799
Author(s):  
Jessica Pollard ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Susana C. Raimondi ◽  
Betsy A. Hirsch ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Gemtuzumab Ozogamicin ◽  
Phase Iii ◽  
Study Entry ◽  
Cell Transplant ◽  
Event Free Survival ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
Pediatric Aml ◽  
To Receive

Abstract CD33 is variably expressed on acute myeloid leukemia (AML) blasts and is the target of gemtuzumab ozogamicin (GO). We previously demonstrated the clinical benefit of GO treatment in children with AML treated on COG AAML0531 in which patients were randomized to receive standard Medical Research Council-based chemotherapy with or without GO. We also demonstrated that CD33 expression is highly variable in pediatric AML and that children with 11q23 translocations involving the KMT2A gene, previously known as the mixed lineage leukemia gene and referred to here as MLL+, have significantly higher CD33 expression, as defined by mean fluorescent intensity (MFI) values, than patients without 11q23/MLL + leukemia (MLL-) [median CD33 MFI: MLL + 229.13 (range 6-1351) vs. MLL-129 (range 2.68-1225.87) P <0.001.] Given significantly elevated levels of CD33 expression in MLL + AML and our previous findings showing an association between high CD33 expression and improved response to GO, we evaluated MLL + AML patients treated on COG AAML0531 to determine whether GO treatment improved their clinical outcomes. COG AAML0531 included 1022 eligible patients ages 1 month-29.99 years of which 215 harbored a 11q23/MLL rearrangement that was confirmed by central cytogenetic review (including G-banding and FISH). Analysis of overall outcomes revealed similar complete remission (CR) rates after Induction I for MLL + and MLL-patients (71% vs. 73%, P = 0.494). However, MLL + patients had lower 5-year overall survival (OS) and event-free survival (EFS) than MLL-patients (OS 58% vs. 66%, P =0.012, EFS 38% vs. 51%, P =<0.001) as well as higher rates of relapse (RR) (52% vs. 36%, P =<0.001) and lower disease-free survival (DFS) (46% vs. 58%, P =0.002). Of the 215 MLL + patients, 107 were treated with conventional chemotherapy only (No-GO) and 108 with chemotherapy and GO (GO). CD33 expression data from flow cytometry analysis were available for 170 MLL + patients. The median CD33 MFI was similar for MLL + patients on both treatment arms [No-GO: 226.5 (range 6-911), GO 237.345 (range 7.6-1351), P = 0.648]. CR rate was higher for MLL + patients treated with GO vs. No-GO (77% vs. 64%; P =0.035). Evaluation of clinical outcomes for patients in the MLL + cohort by treatment arm revealed a superior outcome for GO recipients. EFS at 5 years from study entry was 48% for patients in the GO group vs. 28% for those in the No-GO group (P =0.002) with a corresponding OS of 64% vs. 53% (P =0.053). MLL-patients had similar EFS and OS regardless of GO exposure (P =0.435 and P =0.861, respectively, Figure 1). In MLL + patients who achieved CR, GO exposure translated to lower RR (40% vs. 66% No-GO, P =0.001) and improved DFS (57% vs. 33% No-GO, P =0.002) demonstrating that MLL + patients receiving GO treatment have improved outcomes. In COG AAML0531 a subset of patients was allocated to receive allogeneic hematopoietic stem cell transplant (HSCT) in 1st CR based on donor availability and risk status. This allowed us to evaluate the effect of HSCT in MLL+ patients in the context of GO exposure as any MLL+ patient with a matched family donor or poor induction response (>15% blasts) underwent HSCT. HSCT was conducted in 19 of 83 MLL+ patients (23%) in the GO group after one course of intensification therapy and in 11 of 73 (15%) patients in the No-GO group. Patients in the GO group who received HSCT consolidation had better outcomes than those not receiving HSCT. Specifically, MLL+ patients who received HSCT after prior treatment with GO had a RR of 28% at 5 years from HSCT compared with a RR of 73% for MLL + patients who received HSCT without GO prior (P =0.006). The corresponding DFS at 5 years from HSCT for patients in the GO and No-GO groups was 72% vs. 27% (P =0.004) respectively. These results highlight that the clinical impact of induction GO maintains clinical significance in the post-HSCT setting. Our analysis of data from AAML0531 suggests that pediatric MLL + AML might benefit from the addition of GO to conventional chemotherapy. HSCT might further enhance GO benefit in this subset of patients. Future studies, utilizing GO or other novel CD33 targeted agents, should be considered for MLL + pediatric AML given the superior outcomes observed. Figure 1. Event-free survival from study entry for 11q23/MLL + vs. MLL - patients by treatment arm (GO vs. No-GO). Figure 1. Event-free survival from study entry for 11q23/MLL + vs. MLL - patients by treatment arm (GO vs. No-GO). Disclosures Aplenc: Sigma Tau: Honoraria. Loken:Hematologics Inc.: Equity Ownership.

scholarly journals Evaluation of pulse wave velocity for predicting major advanced cardiovascular events in patients with chronic myocardial infarction

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Z Meiszterics ◽  
T Simor ◽  
R J Van Der Geest ◽  
N Farkas ◽  
B Gaszner
Keyword(s):  
Myocardial Infarction ◽  
Regression Analysis ◽  
Cardiovascular Events ◽  
Pulse Wave ◽  
Cox Regression ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract Introduction Increased aortic pulse wave velocity (PWV) as a strong predictor of major advanced cardiovascular events (MACE) has a prognostic relevance in patients after myocardial infarction (MI). Several non-invasive methods have been proposed for the assessment of arterial stiffness, but the PWV values show significant differences according to the applied techniques. Cardiac magnetic resonance imaging (CMR) provides an accurate method to measure PWV and infarct size in patients after MI. Purpose Calculated PWV values of CMR based phase-contrast (PC) and invasively validated oscillometric methods were compared in this prospective observational study. We aimed to evaluate the cut-off PWV values for each method, while MACE predicted and validated the prognostic value of high PWV in post-infarcted patients in a 6-year follow-up. Methods 3D aortic angiography and PC velocity imaging was performed using a Siemens Avanto 1,5 T CMR device. Oscillometric based Arteriograph (AG) was used to assess PWV using direct body surface distance measurements. The comparison between the two techniques was tested. Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization. Event-free survival was analysed using Kaplan-Meier plots and log-rank tests. Univariable and multivariable Cox regression analysis was performed to identify outcome predictors. Results 75 patients (56 male, 19 female, average age: 56±13 years) referred for CMR were investigated, of whom 50 had coronary artery disease (CAD) including 35 patients with previous MI developing ischaemic late gadolinium enhancement (LGE) pattern. AG and CMR derived PWV values were significantly correlated (rho: 0,343, p&lt;0,05), however absolute PWV values were significantly higher for AG (median (IQR): 10,4 (9,2–11,9) vs. 6,44 (5,64–7,5); p&lt;0,001). Bland Altman analysis showed an acceptable agreement with a mean difference of 3,7 m/s between the two measures. In patients with CAD significantly (p&lt;0,01) higher PWV values were measured by AG and CMR, respectively. During the median follow-up of 6 years, totally 69 MACE events occurred. Optimized PWV cut-off values for MACE prediction were calculated (CMR: 6,47 m/s; AG: 9,625 m/s) by receiver operating characteristic analysis. Kaplan-Meier analysis in both methods showed a significantly lower event-free survival in case of high PWV (p&lt;0,01, respectively). Cox regression analysis revealed PWV for both methods as a predictor of MACE (PWV CMR hazard ratio (HR): 2,6 (confidence interval (CI) 1,3–5,1), PWV AG HR: 3,1 (CI: 1,3–7,1), p&lt;0,005, respectively). Conclusions Our study showed good agreement between the AG and CMR methods for PWV calculation. Both techniques are feasible for MACE prediction in postinfarcted patients. However, different AG and CMR PWV cut-off values were calculated to improve risk stratification. FUNDunding Acknowledgement Type of funding sources: None. Agreement between the two methods Kaplan-Meier event curves for MACE

Survival and toxicity outcomes in patients age 40 or older with relapsed metastatic germ cell tumors (mGCT) treated with high-dose chemotherapy (HDCT) and autologous peripheral-blood stem cell transplant (PBSCT).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 522-522
Author(s):  
Nabil Adra ◽  
Costantine Albany ◽  
Rafat Abonour ◽  
Mohammad Issam Abu Zaid ◽  
Dannillo Pereira ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Indiana University ◽  
Free Survival ◽  
Kaplan Meier

522 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity which can be more pronounced in older patients. We report survival and toxicity outcomes in pts with relapsed mGCT age ≥ 40 at time of HDCT. Methods: 440 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University (IU) between 2004-2017 per our previous reported regimen (N Engl J Med 2007; 357: 340-8). Kaplan-Meier methods were used for progression free survival (PFS) analysis. Results: 110 pts were age ≥ 40 while 330 pts were age < 40. Among pts age ≥ 40, median AFP was 6.6 (range, 1-2,709) and median hCG was 5.3 (range, 1-42, 453). Of the 110 pts age ≥ 40, 75 had complete remission without relapse during a median follow-up of 23 months. There were 3 treatment-related deaths. Conclusions: HDCT plus PBSCT is safe and effective salvage therapy in pts age ≥ 40 with relapsed mGCT. [Table: see text]

Novel Conditioning Regimen for Haploidentical Hematopoietic Cell Transplant for Severe Aplastic Anemia in Children

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5651-5651 ◽  
Author(s):  
Hasan Hashem ◽  
Rawad Rihani ◽  
Eman Khattab ◽  
Mayada Abu Shanap ◽  
Abdelghani Tbakhi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Stem Cell Source ◽  
Cell Source

New hematopoietic cell transplant (HCT) approaches are urgently needed for patients with severe aplastic anemia (SAA) who lack an HLA-identical donor. Haploidentical HCT with post transplant cyclophosphamide (PTCy) represent a potential universal available option for almost all children with SAA. We present a novel conditioning regimen for haploidentical HCT in children with SAA in a center where horse ATG is not available. Conditioning regimen consists of rabbit ATG 2.5 mg/kg/day from day -9 to -7, Fludarabine 30 mg/kg/day from day -6 to -2, Cyclophosphamide 14.5 mg/kg/day from day -6 to -5, Thiotepa 5 mg/kg/day from day -4 to -3, and 4 Gy TBI on day -1 in in two fractions. GvHD prophylaxis consist of PTCy 50 mg/kg/day on days +3 and +4 along with Cyclosporine A and Mycophenolate mofetil (MMF) starting on day +5. Four consecutive children with SAA referred to our center for haploidentical HCT starting in 2018. Median age at HCT was 9 years (5-16) with 3 males and 1 female. All patients were heavily transfused with both blood and platelets prior to referral for HCT. Two patients had strong and one had weak positive anti-HLA antibodies (DSAs) and received desensitization with IVIG, Rituximab and plasmapheresis. One patient received buffy coat infusion on day -1 due to persistent strong DSAs despite desensitization. Median CD34+ dose received was 12 x 10e6, and median CD3+ dose was 29 x 10e6. Donors were all same blood group to patients. All patients successfully engrafted neutrophils at median of 13 days (12-14). Platelets engraftment in 3/4 patients at median of 7 days (5-10). All patients received peripheral blood as stem cell source. Three of four patients survived and doing well at last follow up. One patient had toxic death on day +38 due to chemotherapy related toxicity causing multi-organ failure. Chimerism analysis was full donor in all four patients at median follow up time of 11 months (2-12). Patients were sent home at median of 24 days post HCT. None developed grade 2-4 acute GvHD nor chronic GvHD. Acute GvHD of skin grade 1 stage 1 developed in 2 patient and managed with topical steroids. Viral reactivations consisted of CMV viremia and BK hemorrhagic cystitis in all patients, and have all resolved. No post transplant autoimmune complications. Haploidentical HCT with PTCy represents a quick and first line approach in heavily transfused children with SAA. Although yet limited number of patients, this regimen is feasible and appears to be safe. A great advantage of this regimen is the rapid engraftment of both neutrophils and platelets. Moreover, although using peripheral blood as a stem cell source, there was no severe acute or chronic GvHD. Disclosures No relevant conflicts of interest to declare.

Intention to Treat Analysis of Real-World Outcomes Following Tisgenlecleucel Therapy for Pediatric and Young Adult ALL through a National Access Programme

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Sara Ghorashian ◽  
Caroline Furness ◽  
Michelle Cummins ◽  
John A Snowden ◽  
Maeve A O'Reilly ◽  
...  
Keyword(s):  
Treatment Failure ◽  
B Cell ◽  
Event Free Survival ◽  
Cell Recovery ◽  
Treatment Allocation ◽  
Free Survival ◽  
Intention To Treat ◽  
Kaplan Meier ◽  
Access Programme

Background: Tisagenlecleucel was approved in Europe for relapsed/refractory acute lymphoblastic leukemia (ALL) in young patients in 2018. In England, a national CAR T cell panel (NCCP ALL) ensures equity of access and assesses eligibility using inclusion and exclusion criteria based on the ELIANA study. All UK cases are discussed. Eligible cases are allocated to one of 9 JACIE-FACT IEC-approved centres based on age-appropriate service, capacity, distance and patient preference. We systematically reviewed all cases from panel inception providing an opportunity to analyse complete real-world ALL outcomes from this national access programme for tisagenlecleucel on an intention-to-treat (ITT) basis. Methods: We included all patients discussed in the NCCP ALL from Nov 2018 up to July 16th 2020. Clinical data were retrospectively reported in a standardised dataset to allow central analysis of disease and toxicity-related outcomes. Survival outcomes were assessed as for other CAR studies, using Kaplan-Meier estimates of survival from infusion. These included overall survival (interval to death from any cause) and event-free survival as defined in the ELIANA study (interval to death, disease relapse, or treatment failure defined in turn as failure to respond by day 30, with patients receiving further therapy being censored). In order to report outcomes on an ITT basis, survival outcomes were also assessed from time of treatment allocation for all patients considered eligible for tisagenlecleucel. Further, a more comprehensive event-free survival measure encompassing interval to molecular or frank relapse, further therapy, B cell recovery, death or treatment failure was analysed. Median follow up was calculated using a reverse Kaplan-Meier method. Results: Figure 1 demonstrates all patients: 66 patients were screened, 60 patients were deemed eligible for therapy (the ITT cohort), 57 patients were harvested and 49 infused. A total of 3 patients were not harvested and 2 not infused because of progressive disease (n=4) and 1 manufacturing failure. Patient and disease characteristics are summarised in Table 1. The cohort comprised patients with advanced ALL, having been treated with a median of 2.5 therapy lines not including HSCT (range 1-6), and with 47.5% of the cohort having had a prior HSCT. The median follow-up from infusion was 9.9 months and from treatment allocation for the ITT cohort was 11.9 months. The median lead time from allocation to infusion was 2 months. The CR/CRi rate was 95% in the first 90 days, 78.9% were MRD-. On an ITT basis, CR/CRi rate was 84.8%. Median OS and EFS as defined in the ELIANA study were not reached. Overall survival at 6 and 12 months for infused patients was 97.6% and 86.1%, and for the ITT cohort was 90.4% and 78.3%. EFS for infused patients at 6 and 12 months were 74.8% and 68.2%, and for the ITT cohort were 78.5% and 60.9%. Of 49 patients infused, 14 (28.5%) received further therapy including 6 (8.2%) who received allogeneic SCT for relapse or B cell recovery. For patients relapsing following CR (n=10 infused) there were 4/10 CD19- relapses. A composite EFS including molecular or frank relapse, further therapy, B cell recovery, death or treatment failure was analysed. Using this more stringent definition from infusion, the 6, 12 month EFS were 47.6%, and 33.6% and from treatment allocation for the ITT cohort were 63% and 34.3% Toxicity outcomes are summarised in Table 2. Severe (grade ≥3) CRS, neurotoxicity, infection or cytopenia after day 30 post infusion occurred in 20.4%, 10.2% 27.1% and 54.2% respectively. 71.4% of the cohort developed hypogammaglobulinaemia, (Figure 3A). The 6 and 12 month probabilities of B cell depletion were 67.1% and 51.3% respectively. Conclusions: Whilst registry data provide outcomes of large cohorts receiving Tisagenlecleucel, standardised data collection on complete populations are lacking. The framework of a national access scheme provides a unique opportunity to study outcomes on an ITT basis. The CR and MRD negative CR rates, as well as conventional EFS and OS and severe toxicities noted in our cohort compare favourably to published registry reports (Grupp et al., 2019). We found a greater proportion of CD19+ compared to CD19- relapses than noted in the ELIANA study. Consideration of OS and EFS on an ITT basis are informative for clinicians when screening patients for eligibility. If selected for presentation at ASH 2020, updated data will be presented Disclosures Ghorashian: Amgen: Honoraria; Novartis: Honoraria; UCLB: Patents & Royalties. O'Reilly:Gilead: Honoraria; Novartis: Honoraria, Other: Travel support. Roddie:Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria. Neill:Novartis: Other: Funded attendance at academic conferences; Celgene: Other: Funded attendance at academic conferences. Pagliuca:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Patel:Novartis: Honoraria, Other: travel support. Hough:Novartis: Other: Travel support.

Excellent Disease-Free Survival after Double Cord Blood Transplantation Using a Reduced Intensity Chemotherapy Only Conditioning Regimen in a Diverse Adult Population.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2048-2048 ◽  
Author(s):  
Karen K. Ballen ◽  
Thomas R. Spitzer ◽  
Beow Yeap ◽  
McAfee Steve ◽  
Bimalanghsu R. Dey ◽  
...  
Keyword(s):  
Cord Blood ◽  
Aplastic Anemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Free Survival ◽  
Cord Blood Unit ◽  
Disease Free ◽  
Reduced Intensity

Abstract Umbilical cord blood is a useful stem cell source for patients without matched related or unrelated donors. However, single cord blood unit transplantation in adults is associated with high transplant related mortality, mostly due to infection. In this study, we used a reduced intensity conditioning regimen followed by infusion of two partially matched cord blood units. The conditioning regimen was fludarabine 30mg/m2/day x 6 days, melphalan 100mg/m2/day x 1 day, and rabbit antithymocyte globulin 1.5 mg/kg/day x 4 days. Cord blood units were a 4/6 or better HLA match or better with each other and with the patient, and contained a minimum combined pre-freeze cell dose of 3.7 x 107NC/kg. GVHD prophylaxis was cyclosporine and mycophenolate mofetil. Twenty-one patients, 15 males (71%) and 6 females (29%), median age 49 years (range 24–63 years) participated in a Phase I study. The diagnoses were AML (n=8), ALL (n=1), NHL (n=5), CLL (n=2), MDS (n=2), Hodgkins Disease (n=2), and aplastic anemia (n=1). Fifteen percent of patients were non Caucasian. The cell doses infused were a median of 4.0 x107 NC/kg (range 3.0–5.3 x107) and 2.0 X105 CD34+ cells/kg (range 0.6–10.0 x105). Two patients (both with MDS complicating aplastic anemia) experienced primary graft failure, and received successful second cord blood transplants using a different conditioning regimen. Among the remaining 19 patients, the median time to an absolute neutrophil count >500 was 20 days (range 15–34 days). The median time to a platelet count >20,000 unsupported were 41 days (range 21–125 days). One patient experienced a secondary graft failure, and is well following infusion of previously stored autologous cells. 4 patients (21%) experienced Grades II-IV acute GVHD, and only one patient (5%) experienced Grade III GVHD. There were no patients with Grade IV GVHD and no deaths from acute GVHD. Twelve patients were evaluable for chronic GVHD, and 3 patients (25%) had chronic GVHD of which one case was extensive disease. The 100 day transplant related mortality was 14%. The deaths were due to a CNS bleed, Epstein Barr virus lymphoproliferative disorder, and staphylococcal sepsis. Chimerism analysis showed predominance of one cord by Day +100 in 79% of patients evaluable for 100-day follow-up. In 85% of these patients the first cord blood unit infused predominated. One patient has had progressive disease. With a median follow-up of 7 months (range 2–16 months), the overall survival is 79% and the disease-free survival is 64%. The projected one year disease-free survival is 64%. In conclusion, 1) engraftment of adult patients appears to be acceptable using double cord blood products and reduced intensity, non TBI conditioning regimen; 2) the risk of serious acute and chronic GVHD is low, 3) patients with aplastic anemia/MDS may require more intensive immunosuppression to allow engraftment, 4) GVL appears to be preserved despite the low T cell dose.

Similar Survival after Bone Marrow Versus Peripheral Blood Stem Cell Transplantation from Matched Unrelated Donors in Children with Hematologic Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2066-2066
Author(s):  
Roland Meisel ◽  
Hans-Juergen Laws ◽  
Stephan Balzer ◽  
Benedikt Bernbeck ◽  
Christof Kramm ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Event Free Survival ◽  
Free Survival ◽  
Stem Cell Source ◽  
Detectable Difference ◽  
Unrelated Donors ◽  
Recipient Age

Abstract Peripheral blood stem cells (PBSC) are increasingly used instead of bone marrow (BM) for allogeneic haematopoietic stem cell transplantation (alloHSCT) in children. Prior studies in adults have suggested a comparable outcome with both stem cell sources in matched unrelated donor (MUD) transplantation. However, relative benefits of PBSC versus BM transplantation may substantially differ in children and adults due to a greater propensity to GvHD in older patients and a higher proliferation rate of blasts in childhood leukemia. Here we present the first comparison of the outcome following PBSC vs. BM transplantation from HLA-matched unrelated donors in an entirely pediatric cohort. Between 1992 and 2004, a total of 61 pediatric patients (pts) with haematologic malignancies underwent PBSC (n=38) or BM (n=23) transplantation from ≥ 5/6 HLA antigen-matched unrelated donors following myeloablative conditioning at our institution. PBSC and BM groups were comparable with regard to GvHD prophylaxis, disease category, disease status at transplant and recipient age, while differences were detected in recipients sex (more male pts in PBSC group, p=0.06), conditioning regimen (more busulfan-based conditioning in PBSC group, p=0.01) and median year of transplant (PBSC transplantations were more recent, p=0.001). Engraftment was achieved significantly faster after PBSC compared to BM transplantation (p=0.001). Median time to neutrophil engraftment was 18 (range: 9–28) and 24 (14–43) days for the PBSC and BM cohort, respectively. The rate of acute GvHD grade III/IV (PBSC vs. BM: 28.9% vs. 19.0%, p=0.54) and chronic GvHD (63.0% vs. 56.3%, p=0.75) was comparable between both groups. While there was a statistically non-significant trend towards increased risk of clinically extensive chronic GvHD following PBSC transplantation (48.1% vs. 25.0%, p=0.2), this did not translate into any detectable difference in treatment-related mortality (PBSC vs. BM: 28.9% vs. 26.1 %) or death of disease (21.7% vs. 21.1%) (p=1.0). With a median follow up of 3.4 years (PBSC) and 10.0 years (BM) overall survival (PBSC vs. BM: 47.5 ± 8.6 % vs. 51.8 ± 10.5 %; p = 0.88) and event-free survival (43.3 ± 8.3 % vs. 51.8 ± 10.5 %; p = 0.60) is without detectable difference between both groups. This result was confirmed in a multivariate analysis including stem cell source, recipient age, recipient sex, conditioning regimen, disease status at transplant and year of transplant as covariates, showing that advanced disease status at transplant is the only significant, independent risk factor for overall mortality (RR 2.4, 95%-CI 1.1–5.2, p=0.02). In conclusion, our data provide evidence that in pediatric recipients of MUD transplantation the use of PBSC instead of BM leads to a faster neutrophil engraftment and a trend towards higher incidence of extensive chronic GvHD. As overall survival and event-free survival is comparable when using PBSC and BM, PBSC is a valid alternate stem cell source for pediatric alloHSCT from MUDs. Supported by the Elterninitiative Kinderkrebsklinik e.V., Duesseldorf

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