Long-Term Outcome of Children with Acute Myeloid Leukemia in First Remission Given Allogeneic HSCT from a Matched Family Donor After a Conditioning Regimen Comprising Busulfan, Cyclophosphamide and Melphalan.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2288-2288
Author(s):  
Marco Zecca ◽  
Riccardo Masetti ◽  
Adriana Balduzzi ◽  
Franca Fagioli ◽  
Giorgio Dini ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
De Novo ◽  
Alkylating Agents ◽  
Conditioning Regimen ◽  
Allogeneic Hsct ◽  
First Remission ◽  
De Novo Aml ◽  
Family Donor

Abstract Abstract 2288 Poster Board II-265 Background. More than 80% of children with de novo acute myeloid leukemia (AML) achieve complete remission (CR) after aggressive induction chemotherapy. However, post-remission treatment plays a crucial role in the final outcome of these patients. In this regards, possible post-remission treatments include high dose chemotherapy, as well as autologous or allogeneic hematopoietic stem cell transplantation (HSCT). In the last years, several groups have compared allogeneic HSCT with chemotherapy or autologous HSCT in adults as well and children with AML in first remission. These studies have demonstrated that allogeneic HSCT is superior to the other forms of post-remission therapy in children with AML not carrying favourable cytogenetic characteristics. We herein report the long-term results of a prospective multicenter study aimed at evaluating the safety and efficacy of an original combination of 3 alkylating agents, busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) as conditioning regimen for patients affected by de novo AML other than the FAB M3 subtype and given allogeneic HSCT from a matched family donor in first haematological CR. Patients and methods. Seventy consecutive patients (40 males and 30 females), affected by de novo AML in first CR, received an allogeneic HSCT from a HLA-matched family donor after a conditioning regimen combining BU (4 mg/Kg/day for 4 days), CY (60 mg/Kg/day for 2 days) and L-PAM (140 mg/m2). BU dosage was adjusted after the pharmacokinetic study performed following the first administration, in order to maintain a concentration to the steady state (Css) comprised between 600 and 900 ng/mL. Transplants were performed in one of the transplant centers of the Italian Association for Pediatric Hematology / Oncology (AIEOP) between 1992 and 2002. Median patient age at HSCT was 7 years (0.5 – 17). Two patients had FAB M0 AML, 25 M1, 17 M2, 12 M4, 21 M5, 1 M6 and 2 M7 AML. Children with M3 AML were excluded from the study. Five patients with CBF anomalies, either isolated or associated with loss of sex chromosome, were considered to have favourable cytogenetics. The median interval between diagnosis and HSCT was 3.9 months (2.9 - 9). All patients were given bone marrow stem cells. GVHD prophylaxis consisted of cyclosporine-A (Cs-A) alone in 89% of patients, the remaining children receiving a combination of Cs-A with short-term methotrexate. Results. Median follow-up for surviving patients is 9 years (range, 6 – 16 years). The conditioning regimen was well tolerated, and no patient died for causes directly attributable to the myeloablative treatment. All patient engrafted, the median time to reach neutrophil and platelet recovery being 13 (7 - 28) and 21 (13 – 115) days, respectively. The cumulative incidence (CI) of grade II-IV acute GVHD was 58% (48 – 71), while that of grade III-IV acute GVHD was 14% (8 – 25). Chronic GVHD incidence was 27% (18 – 39). Ten-years survival probability was 77% (67 - 87), while 10-years disease-free survival (DFS) was 76% (65 - 86). The cumulative incidence of relapse was 17% (10 – 29), while the cumulative incidence of transplant-related mortality was 7% (3 – 17). Results improved over time, DFS being 59% (41 – 78) for patients transplanted before 1997 and 86% (75 – 96) for those transplanted after 1997. No other variables influenced the probability of both survival and DFS. Conclusions. Our study, conducted on a significant number of children affected by AML in first CR and with a very long follow-up demonstrate that allogeneic HSCT from a matched family donor can cure a large proportion of patients. The combination of dose-adjusted BU, CY and L-PAM was safe and well tolerated, with an incidence of TRM of only 7% and no death directly attributable to the conditioning regimen. Furthermore, the combination of 3 alkylating agents showed a good anti-leukemic activity, the probability of leukaemia recurrence being only 17%. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-Term Clinical Outcomes of Allogeneic Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1968-1968
Author(s):  
Elena Zamagni ◽  
Giuseppe Bandini ◽  
Annalisa Pezzi ◽  
Paola Tacchetti ◽  
Ilaria Rizzello ◽  
...  
Keyword(s):  
Male Patient ◽  
Cumulative Incidence ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Sibling Donor ◽  
Patient Gender ◽  
Risk Of Progression ◽  
Female Donor

Abstract Allogeneic stem cell transplantation (allo-SCT), which provides a tumor-free graft, is an alternative approach to autologous transplantation for multiple myeloma (MM) that offers the possibility of cure through a graft vs myeloma effect (GVM). However, the inherent non relapse mortality (NRM) and the high post-transplant relapse rate are the major shortcomings of this strategy which continues to have a controversial role in MM treatment. To highlight the long-term clinical outcomes of allo-SCT, we performed a retrospective analysis on 102 patients (pts) with MM who received at our Institution either a myeloablative (MA) (74 pts) or a non-myeloablative (NMA) (28 pts) conditioning regimen between 1990 and 2014. The MA regimen consisted in low dose TBI and cyclophosphamide (cyclo) ± melphalan (mel) or busulfan-cyclo. The NMA regimen was mel-fludarabine. Graft versus host disease (GVHD) prophylaxis consisted in cyclosporine + methotrexate (83%) or mycophenolate (17%), with the addition of thymoglobulin for unrelated or related female vs male recipient donors. The median age was 42 yrs (IQR 38-47), 60% pts were male. The hematopoietic cell donors were sibling in 77 pts and unrelated in 25, while the source of stem cells was peripheral blood in 65 and bone marrow in 37 pts. Fifty-six pts received allo-SCT as first-line therapy, 31 as second-line and 13 as third or fourth-line. Median time from diagnosis to allo-SCT was 22 months. Response status at the time of transplant was at least PR in 63% of the pts, including ≥ VGPR in 36% and CR in 12%. Overall, the response rate after allo-SCT was as follows: CR 58%, VGPR 19%, PR 18%. Median CR duration was 10 years (44% at 15 years). The incidence of acute grade II-IV and III-IV GVHD was 25% and 15%, respectively. The incidence of all grades chronic cGVHD was 48%, grade ≥2: 24%, with a median onset time of 178 days. By competitive risks analysis, the cumulative incidence of cGVHD at 1 and 3 years was 20% and 32%, respectively. On univariate analysis, the gender combination of female donor-male patient resulted in significantly higher incidence of cGVHD (sub hazard ratio, SHR, 2.3, P= 0.03). The cumulative incidence of NRM was 6.6% at 100 days, 11% at 1 year and 14.4% at 3 years, with lack of statistically significant relationship with the conditioning regimen. By univariate analysis, < PR prior to allo-SCT (SHR 2.8) and all grades cGVHD (SHR 4.6) were significantly associated with an increased NRM. By competitive risks analysis, the cumulative incidence of relapse was 50% at 5 years, 58% at 10 years and 59% at 15 years. On univariate analysis, sibling donor (SHR 0.54, P=0.047), all grades cGVHD (SHR 0.5, P=0.011) and ≥VGPR after allo-SCT (SHR 0.38, P=0.001) were significantly associated with extended time to progression. All grades cGVHD (SHR 0.43, P=0.005) and ≥VGPR after allo-SCT (SHR 0.36, P= 0.001) were independent predictors for a lower risk of progression on multivariate analysis. With a median follow-up of 13 years, overall survival (OS) was 43% at 5 years and 34% at 10 years. In univariate analysis, low ISS stage at diagnosis, sibling donor, absence of female donor-male patient gender combination, ≥VGPR prior to allo-SCT and first-line allo-SCT were significantly related to OS. Multivariate analysis confirmed an OS benefit for having a sibling donor (HR 0.30, P<0.001), absence of female donor-male patient gender combination (HR 0.51, P=0.022) and being in ≥ VGPR prior to allo-SCT (HR 0.41, P=0.003). In conclusion, this retrospective analysis performed with an extended follow-up of 13 years shows that a fraction of MM pts can be long-term survivors after allo-SCT, one third of them being potentially cured. The best outcomes were obtained when allo-SCT was applied in pts in an early phase of their disease and with a small residual tumor size. The major challenge, both with MA and NMA allo-SCT, was the relatively high post-transplant relapse rate. The presence of cGVHD was protective for the risk of progression, supporting the role of GVM, but increased the risk of NRM. New approaches aimed at modulating cGVHD are warranted. In addition, incorporation of novel agents before and after allo-SCT to increase the rate and duration of high-quality responses, as well as identification of those patients mostly benefiting from this procedure, will likely contribute to improve long-term outcomes. Disclosures Zamagni: Celgene Corporation: Honoraria, Speakers Bureau; Janssen Pharmaceuticals: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Cavo:Sanofi: Consultancy, Honoraria; Onyx: Honoraria; Jansenn: Consultancy, Honoraria; Millenium Pharmaceuticals: Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS: Honoraria.

Nonmyeloablative Allogeneic Transplantation (NMT) for Relapsed Follicular Lymphoma (FL): Continuous Complete Remission with Longer Follow-Up.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 485-485
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Martin Korbling ◽  
Chitra Hosing ◽  
Luis Fayad ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Time ◽  
De Novo ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Study Entry ◽  
Two Samples

Abstract NMT carries the promise of long-term disease control in FL by graft-versus-lymphoma immunity. We investigated the long-term efficacy of this strategy. Between March 1999 and April 2005, 47 consecutive patients were enrolled, ranging in age from 33 to 68 years (median, 53 years). The time from diagnosis to transplantation ranged from 7 months to 24 years (median, 3 years). All patients had recurrent chemosensitive FL. Each patient had received 2 to 7 (median, 2) chemotherapy regimens. Eight patients (17%) had failed a prior autologous transplantation. At the time of transplantation, 29 patients (61%) were in PR, and 18 (31%) were in CR. The conditioning regimen consisted of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days) and rituximab (Khouri, Blood 2001). This was followed by an infusion of HLA-matched hematopoietic cells from related (n=45) or unelated donors (n=2). Tacrolimus and methotrexate were used for graft-versus-disease (GVHD) prophylaxis. All patients achieved CR after transplantation. The median time to achieve CR in patients who had evidence of active disease at study entry was 5.5 months. Two relapses occurred. One was observed at 18 months; this patient responded to DLI with a continuous CR at 24+ months. The other patient who developed a relapse, was found to be simultaneously in graft failure 20 months after his transplantation. That patient was treated with rituximab and is still in CR at his last follow-up 4 years later. Eighteen patients had PCR evidence of bcl-2 translocation in the bone marrow at study entry. There were a total of 100 bone marrow post-treatment PCR samples available for analysis. Ninety eight samples that are drawn at a median time of 45 months after transplantation (range 4 months to 72 months) showed a negative PCR result. Two samples from 2 different patients were PCR-positive early after transplant; they became PCR-negative 3 months later. With a median follow-up time of 56 months (range, 19–94 months), the estimated overall survival (OS) and current progression-free survival (CPFS) rates at 6 years were 85% (95% confidence interval [CI], 71%–93%) and 83% (95% CI 69%–91%), respectively. The incidence of acute grade II–IV GVHD was 11% (95% CI, 31%–66%). The incidence of chronic extensive and limited GVHD, was 51% (95% CI, 44%–78%). Of the 28 patients who developed chronic GVHD, 20 (71%) had a de novo onset. The median time of onset of chronic GVHD was 262 days after transplantation, and the OS of patients with chronic GVHD was 89%, with a median follow-up time of 57 months (range, 19–94 months). Only five patients of the whole study group are still receiving immunosuppressive therapy at the time of their last follow-up. In conclusion, the longer follow-up of our study does provide further insight into long-term disease activity and regimen toxicity of NMT for FL, laying the groundwork for prospective comparative trials. We believe that the described results are a step forward toward finding a cure for this disease.

scholarly journals Long-Term Outcome of Children with Acute Leukemia (AL) Given Alphabeta T and B-Cell Depleted HLA-Haploidentical Hematopoietic Stem Cell Transplantation (TBdepl-haploHSCT)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 799-799
Author(s):  
Pietro Merli ◽  
Daria Pagliara ◽  
Mattia Algeri ◽  
Federica Galaverna ◽  
Giuseppina Li Pira ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Advisory Committees ◽  
Low Incidence ◽  
Patient’S Outcome

Background: TBdepl-haploHSCT is a suitable option for children with AL in need of an allograft, lacking an HLA-compatible donor. We previously published promising results in a cohort of 80 children with AL, given this type of allograft (Locatelli et al., Blood 2017), demonstrating a low incidence of acute and chronic graft-versus-host disease (GvHD) and low non-relapse mortality (NRM), translating into a final outcome comparable to that of patients transplanted from an HLA-compatible donor. We present the long-term follow-up analysis of this study (NCT01810120), now including 134 patients, with a minimum observation time of 100 days after the allograft. Patients and methods: Between October 2010 and April 2019, 134 children with AL in morphological complete remission (CR) received TBdepl-haploHSCT from an HLA-partially matched relative (a parent in 97% of cases) at Ospedale Pediatrico Bambino Gesù in Rome, Italy. All patients were prepared to the allograft using a fully-myeloablative conditioning regimen including a combination of cytotoxic drugs and/or total body irradiation (TBI). Anti-T-lymphocyte globulin (ATLG) was used before transplantation (12 mg/kg total dose, from days -5 to day -3) to modulate bi-directional donor/recipient alloreactivity. Rituximab (200 mg/sqm) was administered on day -1 to prevent post-transplantation EBV-induced lymphoproliferative disorders (PTLD). No patient received any post-transplant GvHD prophylaxis. Results: Characteristics of patients enrolled in the study are shown in Table 1. Median follow-up of surviving patients is 60 months (range: 3 months - 8.7 years). Only 3 patients did not achieve engraftment (all affected by acute myeloid leukemia and who did not receive TBI during conditioning regimen); median time to neutrophil and platelet recovery was 13 (range 9-22) and 11 (range 8-23) days, respectively. Cumulative incidence of grade II-III acute GvHD was 16.5% (95% CI 9.9-22.6). One patient developed gut GvHD, while for all other patients skin was the sole organ involved; no case of grade IV GvHD was recorded. Eight out of the 123 patients at risk developed chronic GvHD, in all cases of limited severity, the cumulative incidence of this complication being 7.6% (95% CI 2.3-12.6). Six patients died for transplant-related complications (2 because of idiopathic pneumonitis and 1 each of disseminated adenovirus infection, cardiac insufficiency, combined CMV/rhinovirus pneumonia and sepsis from Pseudomonas aeruginosa), the 5-year cumulative incidence of NRM being 4.5% (95% CI, 1.8-9.0). Since 25 patients relapsed at a median time of 173 days (range 59-1012) after HSCT, the 5-year cumulative incidence of relapse is 21.1% (95% CI, 14.2-29.1). The 5-year probability of overall and leukemia-free survival (LFS) were 74.6 (95% CI 65.1 -71.9) and 74.4% (95% CI 65.4-81.4) (Figure 1A), respectively. Use of TBI during the preparative regimen, age at transplant above the median value (Figure 1B) and disease status at transplantation (CR1 and CR2, Figure 1C) were associated with better patient's outcome, because of a reduced incidence of relapse (Figure 1D for TBI). All these 3 factors remained statistically significant in multivariable analysis for LFS: hazard ratio (HR) for TBI was 0.16 (95% CI, 0.06- 0.37, p&lt;0.001, HR for age at HSCT was 0.27 (95% CI, 0.11-0.65, p=0.003), while that for disease status was 0.49 (95% CI, 0.26-0.91, p=0.02), respectively. The 5-year GvHD/relapse-free survival was 69.9% (95% CI 60.8-77.3). The median CD3+ cell count on day +30, +90, +180 and +360 were 187, 215, 660 and 1260/mcl, respectively. Conclusions: These data confirm in a larger population and with a longer follow-up that TBdepl-haploHSCT is a safe and effective transplant option, being associated with a low risk of both NRM and acute/chronic GvHD, resulting into a 5-year LFS comparable or even better with that reported in studies using either an HLA-identical sibling or an unrelated volunteer as donor. In particular, the low incidence of chronic GvHD preserves a good quality of life in patients with long life-expectancy. Leukemia recurrence represents the main cause of treatment failure and strategies based either on the use of a titrated number of donor T cells transduced with a safety switch or ex-vivo depleted of the alloreactive component could further improve patient's outcome. Figure 1 Disclosures Merli: Novartis: Honoraria; Sobi: Consultancy; Amgen: Honoraria; Bellicum: Consultancy. Algeri:Miltenyi: Honoraria; Atara Biotherapeutics: Consultancy, Honoraria; Bluebird bio: Consultancy, Honoraria. Locatelli:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Miltenyi: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Full Donor Chimerism after Allografts for Myelofibrosis: The Role of Conditioning Regimen

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4490-4490
Author(s):  
Patrizia Chiusolo ◽  
Sabrina Giammarco ◽  
Teresa Lamparelli ◽  
Lucia Casarino ◽  
Monica Rossi ◽  
...  
Keyword(s):  
Alkylating Agents ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Group Versus ◽  
Disease Free Survival ◽  
Advisory Board ◽  
Allogeneic Hsct ◽  
Donor Chimerism ◽  
The One

Background : The conditioning regimen for patients with myelolfibrosis undergoing an allogeneic HSCT is usually composed of a combination of fludarabine (FLU) with one alkylating agent, busulkfan (BU), thiotepa (THIO) or melphalan. In a recent prospective randomized study comparing BU-FLU versus THIO-FLU, the proportion of patients with full donor chimerism at 6 months, was respectively 63% and 65% (Patriarca et al, BBMT 2019). Aim of the study. Assess the rate of full donor chimerism in patients with myelofibrosis, after conditioning with one or two alkylating agents. Methods. We analyzed 113 patients with myelofibrosis, for whom chimerism data were available on day +30 . There were two groups: 35 patients were conditioned with either thiotepa-cyclophosphamide , thiotepa-fludarabine or busulfan-fludarabine (ONE-ALK), whereas 78 patients were prepared with thiotepa, busulfan, fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years, p=0.008), were less frequently splenectomized pre-HSCT (30% vs 54%, p=0.03), had more frequently intermediate-2/high DIPSS scores (89% vs 74%, p=0.04) , and had comparable transfusion burden pre-HSCT (p=0.7). Chimerism was assessed via STR (PowerFlex-Promega) Results. The proportion of patients with full donor chimerism on day +30 in the TBF vs the ONE-ALK group was 87% vs 51% (p=0.00002); on day +60 these figures were 93% vs 13% (p<0.0001) and on day +90 , the figures were 90% vs 21% (p<0.00001). Full donor chimerism on day+30 was achieved in 81% of patients with DIPSS int1 (n=16), 74% of patients with int2 DIPSS, and 70% of patients with high risk DIPSS (p=0.6). Acute GvHD grade II-IV occurred in 27% vs 37% of patients in the two groups (p=0.7), and moderate severe chronic GvHD in 20% and 21% (p=0.8). The 5 year cumulative incidence of relapse was 8% in the TBF group, versus 50% for the ONE-ALK group (p<0.0001), whereas the CI of TRM was 25% vs 11% (p=0.1). The 5 year actuarial disease free survival (DFS) was respectively 65% for TBF and 38% for the ONE-ALK group (p=0.004). Complete chimerism day+30. When looking at whether patients had (n=84) or not (n=29) full donor chimerism on day +30, the CI of relapse was respectively 44% vs 15% (p=0.002), the CI of TRM 18% vs 15% (p=0.5), and the 5 year DFS 65% vs 32% (p=0.001). Conclusions. Early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis undergoing an allogeneic HSCT. The combination of 2 alkylating agents in the conditioning regimen, provides a significantly higher chance of achieving full donor chimerism on day+30, and thus long term disease control. Figure Disclosures Angelucci: Vertex Pharmaceuticals Incorporated, and CRISPR Therapeutics: Other: Partecipation in DMC; Roche: Other: Local advisory board; Jazz Pharmaceuticals: Other: Local advisory board; BlueBirdBio: Other: Local advisory board; Novartis: Honoraria, Other: Chair Steering Committee TELESTO protocol; Celgene: Honoraria, Other: Partecipation in DMC.

scholarly journals Long Term Follow up and Impact of Comorbidity Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory AML - Lessons Learned from the Prospective Bridge Trial -

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4692-4692
Author(s):  
Jan Moritz Middeke ◽  
Regina Herbst ◽  
Stefani Barbara Parmentier ◽  
Gesine Bug ◽  
Mathias Hänel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Study Enrollment ◽  
Long Term Follow Up

Abstract In patients with relapsed or refractory (r/r) Acute Myeloid Leukemia (AML), allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered to be the only treatment providing long-term disease control for fit patients. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy prior to HSCT in patients with r/r AML. Here, we report the long-term follow up of this Phase II, multi-center, Intent-To-Transplant study and the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range 40 - 75) were enrolled. Patients were scheduled for at least one cycle of salvage therapy with CLARA (clofarabine 30 mg/m2 and cytarabine 1 g/m2, days 1-5). Chemo-responsive patients with a donor received HSCT after first CLARA. In the event of a prolonged donor search, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine 30 mg/m2, day -6 to -3, and melphalan 140 mg/m2 on day -2. The ECOG score, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and Cumulative Illness Rating scale (CIRS) were obtained at study enrolment as well as prior to HSCT. Sixty-seven percent of the patients received HSCT within the trial. After a median follow up of 40months (95% CI, 38-49 months), the estimated 4-year OS (Figure 1) for all enrolled patients was 38% (95% CI, 28-50%) and Disease-Free Survival for transplanted patients was48% (95% CI, 36-64%). The CIR at four years was 30% (95% CI, 17-43%) and the NRM 22% (95% CI, 10-33%).Those patients who received an allogeneic HSCT within the trial had a median HCT-CI at the time of study enrollment of 1 (range, 0 - 6) compared to a median of 2 (range, 0 - 6) for those who did not proceed to allogeneic HSCT (p = .17). Corresponding figures for the CIRS were a median of 2 (range, 0 - 9) compared to 4 (range, 0 - 8) (p = .09). The median ECOG score was 1 (range, 0 - 3) in both groups. Compared to the time point of study enrollment, both the HCT-CI as well as the CIRS increased to a median of 2 (observed range of score, 0 - 7) and a median of 4 (observed range of score, 0 - 12), respectively, at the time of start of the conditioning regimen. This was almost exclusively due to an increase in infectious complications (Figure 2). Inmultivariate analysis, both the baseline HCT-CI and the ECOG score had a statistically significant impact with a HR of 1.22 (p = .025) and 1.72 (p = .001), respectively, on OS. Using a clofarabine-based salvage therapy combined with early allogeneic HSCT we were able to achieve good long-term results for patients with r/r AML. In this cohort, both the HCT-CI and the ECOG score gave prognostic information on OS, showing feasibility of comorbidity evaluation at the time of diagnose of r/r AML. Figure 1 OS of all enrolled patients Figure 1. OS of all enrolled patients Figure 2 Changes of the HCT-CI at baseline to HSCT Figure 2. Changes of the HCT-CI at baseline to HSCT Disclosures Middeke: Sanofi: Honoraria. Rösler:Janssen: Consultancy, Other: Travel/Accommodation/Expenses. Thiede:AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.

Outcome of Relapsed AML Patients Aged between 50 and 70: The ALFA Group Experience (ALFA 9801 Study).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1857-1857
Author(s):  
F. Merabet ◽  
N. Boissel ◽  
O. Reman ◽  
Jean-Henri Bourhis ◽  
B. Quesnel ◽  
...  
Keyword(s):  
De Novo ◽  
High Dose ◽  
Conventional Dose ◽  
Investigational Drugs ◽  
Group 12 ◽  
First Remission ◽  
First Relapse ◽  
De Novo Aml ◽  
Lost To Follow Up

Abstract Background: Outcome of relapsing AML pts aged &gt; 50 yrs is considered poor but remains incompletely studied and is important to analyse, especially with new therapeutic perspectives like targetted drugs and non myeloablative allogeneic SCT (ASCT). Methods: we analyzed the outcome of pts included in ALFA 9801 trial (reported in detail in another abstract) who had relapsed. This trial included, between 2001 and 2006, de novo AML aged 50 to 70 years, randomized for induction to conventional dose AraC and high dose DNR or IDA, followed by 2 courses of intermediate dose AraC with the same anthr, and finally randomization between no maintenance or 1 year of IL2. Results: 468 pts were included (median age: 60 years).360 (77%) achieved CR. With a median follow up of 40 months, 232 (64% of CR) pts had relapsed. Their median age was 60 years and M/F 132/100. Duration of first remission was ≤6 mo (41pts), &gt;6mo and ≤12 mo (102 pts), &gt;12 mo (89 pts). Treatment received for relapse was proposed at the discretion of physicians in charge of the patient: 97 (42%) pts received intensive chemotherapy (anthr-AraC, n=89, HD AraC n=5, FLAG, n= 3),) (IC group), 47 (20%) received Gemtuzumab (GO) alone (n= 25) or a GO containing regimen (n=22)(GO group), 12 patients (5%) received LD AraC, and 60 (28%) were treated with supportive care (SC). 8 pts were lost to follow up, 3 pts had CNS relapse, 1 pt received ASCT as relapse tratment, and 4 received investigational drugs. 52/110 pts aged &lt; 60 received IC or GO combining regimen versus 39/122 pts&gt; 60 (p&lt;0.01). 46/122 pts aged &gt; 60 were treated with SC versus 12/110 pts&lt;60 (p&lt;0.001). GO alone was given to 22/110 and 20/122 pts aged &lt; or &gt; than 60 (NS). 18 patients (median age 53 years) received allo SCT (13 “classical” and 5 non myeloablative SCT) in second CR, including only 1 pt aged &gt; 60. A second CR was obtained in 39%: 57% in the IC group, 59% in the GO group (60% for pts treated with GO alone), 25% in the LDAraC group and none in the SC group. Median duration of second CR was 260 days. Median overall survival of the 232 patients from first relapse was 233 days (IC95%:202–281). Age &lt; 60 years (p= 0.02), duration of first CR&gt; 12 months (median 451 d vs 205 d for 1st CR&lt; 12 months, p=0.001), salvage with IC or GO (median 340 days vs 140 for non IC +GO group, p&lt;0.001) predicted for longer survival. There was no difference in survival for pts in the intermediate (N:144) and defav (N:43) cytogenetic groups (according to results of cytogenetics at diagnosis). The 12 pts in the fav cytogenetic group had significant better outcome. Survival from first relapse was similar for pts with a duration of 1st remission &lt;6 months or 6 to 12 months. Of the 18 pts allografted in 2nd CR: 9 were alive in CR (4 + to 60 +: median:30 months). Conclusion: In this relatively old relapsing AML population (median age of 60), 62% of the 232 pts were able to receive intensive treatment for their relapse (chemotherapy and/or GO). 39% pts overall obtained a 2nd CR, including 57% of those treated intensively.17% of CR2 pts received allogeneic SCT, a proportion that may increase if more non myeloablative allo SCT are performed.

Is 3 years adequate for tracking completely occluded coiled aneurysms?

2020 ◽  
Vol 133 (3) ◽  
pp. 758-764
Author(s):  
Eung Koo Yeon ◽  
Young Dae Cho ◽  
Dong Hyun Yoo ◽  
Su Hwan Lee ◽  
Hyun-Seung Kang ◽  
...  
Keyword(s):  
De Novo ◽  
Careful Monitoring ◽  
Surveillance Period ◽  
Radiological Data ◽  
De Novo Aneurysm ◽  
Low Probability ◽  
Almost All ◽  
Annual Risk

OBJECTIVEThe authors conducted a study to ascertain the long-term durability of coiled aneurysms completely occluded at 36 months’ follow-up given the potential for delayed recanalization.METHODSIn this retrospective review, the authors examined 299 patients with 339 aneurysms, all shown to be completely occluded at 36 months on follow-up images obtained between 2011 and 2013. Medical records and radiological data acquired during the extended monitoring period (mean 74.3 ± 22.5 months) were retrieved, and the authors analyzed the incidence of (including mean annual risk) and risk factors for delayed recanalization.RESULTSA total of 5 coiled aneurysms (1.5%) occluded completely at 36 months showed recanalization (0.46% per aneurysm-year) during the long-term surveillance period (1081.9 aneurysm-years), 2 surfacing within 60 months and 3 developing thereafter. Four showed minor recanalization, with only one instance of major recanalization. The latter involved the posterior communicating artery as an apparent de novo lesion, arising at the neck of a firmly coiled sac, and was unrelated to coil compaction or growth. Additional embolization was undertaken. In a multivariate analysis, a second embolization for a recurrent aneurysm (HR = 22.088, p = 0.003) independently correlated with delayed recanalization.CONCLUSIONSAlmost all coiled aneurysms (98.5%) showing complete occlusion at 36 months postembolization proved to be stable during extended observation. However, recurrent aneurysms were predisposed to delayed recanalization. Given the low probability yet seriousness of delayed recanalization and the possibility of de novo aneurysm formation, careful monitoring may be still considered in this setting but at less frequent intervals beyond 36 months.

scholarly journals Long-term outcomes of fully covered self-expandable metal stents versus plastic stents in chronic pancreatitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sang Hoon Lee ◽  
Yeon Suk Kim ◽  
Eui Joo Kim ◽  
Hee Seung Lee ◽  
Jeong Youp Park ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Clinical Efficacy ◽  
De Novo ◽  
Plastic Stents ◽  
Metal Stents ◽  
Plastic Stent ◽  
Sems Group ◽  
Spontaneous Migration

AbstractChronic pancreatitis (CP) related main pancreatic duct (MPD) stricture has been a challenge for endoscopists. Fully covered self-expandable metal stents (FC-SEMS) has been tried in CP patients, but the efficacy and safety are still controversial. Thus, we aim to compare the long-term clinical efficacy of FC-SEMS vs. plastic stent placement in persistent MPD strictures secondary to CP. Between 2007 and 2018, 80 chronic pancreatitis patients (58 males, median age 49 years), who underwent endoscopic placement of FC-SEMS (n = 26) and plastic stent (n = 54) for persistent MPD strictures after at least 3 months of initial single plastic stenting, were retrospectively analyzed during a median follow-up duration of 33.7 months. As a result, MPD stricture resolution rate was statistically higher in FC-SEMS group (87.0% vs. 42.0%, p < 0.001). Although immediate complications occurred similarly (38.5% vs. 37.0%, p = 0.902), spontaneous migration (26.9%) and de novo strictures (23.1%) were pronounced delayed complications in FC-SEMS group. Pain relief during follow-up was significantly higher in FC-SEMS group (76.9% vs. 53.7%, p = 0.046). The total procedure cost was similar in both groups ($1,455.6 vs. $1,596.9, p = 0.486). In comparison with plastic stent, FC-SEMS placement for persistent MPD strictures had favorable long-term clinical efficacy, with its typical complications like spontaneous migration and de novo strictures.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

Sign in / Sign up

Export Citation Format

Share Document