Long-Term Outcome of Chronic Myelomonocytic Leukemia (CMML) Patients Treated with Hypomethylating Agents (HMA): A Single-Institution Experience

Abstract CMML is a myelodysplastic/myeloproliferative disease considered a separate entity by WHO, but from a therapeutic perspective, most clinicians consider CMML a subtype of myelodysplastic syndromes (MDS), for which hypomethylating agents (HMA) are the standard of therapy. Herein, we report on the long-term outcome of patients with CMML treated with HMA as well as prognostic associated factors. Methods: We reviewed the records of 102 consecutive patients with CMML treated between March 2004 and June 2014. Patients who underwent ASCT were excluded (n=5), and thus a total of 97 patients were analyzed. Responses were assessed according to IWG 2006. Differences among variables were evaluated by the Chi-square test and Mann–Whitney U test for categorical and continuous variables, respectively. Progression-free survival (PFS) was defined as the time from start of therapy to leukemia transformation or death. Overall survival (OS) was defined as the time from start of therapy to death. Patients who were alive were censored at the last follow-up date. PFS and OS were estimated using Kaplan-Meier analysis, and multivariate analysis was performed by Cox regression. Results: Median age at diagnosis was 71 years (50-87). Treatment was azacitidine (AZA) in 30 patients (31%) and decitabine (DEC) in 67 (69%), and they received a median of 6 courses of therapy (1-70). IPSS risk score was low in 18 patients (18.6%), int-1 in 47 (48.5%), int-2 in 23 (23.7%), and high in 4 (4.1%). Fourteen patients (14.4%) had poor-risk cytogenetics. Among patients with available mutation data, we found RAS mutations in 18 out of 79 analyzed cases (22.7%), FLT3-ITD mutations in 3 out of 86 (3.5%), NPM1 mutations in 2 out of 40 (5%), and Jak2 mutations in 1 out of 36 (2.8%). Overall response rate (ORR) was 51%, and best responses to HMA were complete remission (CR) in 51 (52%) patients, partial response (PR) in 3 (3.1%), and hematological improvement (HI) in 7 (7.2%). Median duration of response was 11.5 months (range, 1.1 to 67.5). There was no difference in response rate between DAC and AZA therapies. With a median follow-up of 11 months (1-73), 27 cases (28%) transformed into AML after a median of 19 months (5-59). At the last follow-up, 32 patients (33%) remained alive. The median PFS and OS were 18 and 23 months, respectively. The 1- and 2-year OS rates were 94.7% and 85.6%, respectively, and the 1- and 2-year PFS rates were 92.7% and 81.3%, respectively. By multivariate analysis, patients with higher hemoglobin levels (HR=0.83, 95%CI [0.72-0.97]; p=0.024) and those who achieved CR (HR=0.46 [0.26-0.81]; p=0.007) had better OS, whereas high-risk cytogenetics was associated with poorer OS (HR: 2.89 [1.34-6.21]; p=0.007). Only achievement of CR was an independent factor with impact on PFS (HR: 0.32 [0.18 – 0.55]; p<0.001). We did not identify any independent factor with significant impact on response rate. Conclusions HMA is a suitable therapy for patients with CMML, and the achievement of CR is the most important goal to improve patient outcomes. Disclosures Cortes: Celgene: Research Support Other.

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Long-Term Outcome of Patients with Myelodysplastic Syndromes (MDS) Treated with Hypomethylating Agents (HMA): A Report on Behalf of the MDS Clinical Research Consortium

Blood ◽

10.1182/blood.v124.21.4641.4641 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4641-4641

Author(s):

Elias Jabbour ◽

Koji Sasaki ◽

Mikkael A. Sekeres ◽

Rami S Komrokji ◽

David P. Steensma ◽

...

Keyword(s):

Multivariate Analysis ◽

Median Survival ◽

Regression Models ◽

Low Risk ◽

Intermediate Risk ◽

Term Outcome ◽

Long Term Outcome ◽

Duration Of Response

Abstract Background: Therapy with HMA is now the standard of care for pts with MDS and chronic myelomonocytic leukemia (CMML) with complete response (CR) rates of 7% to 35%, median response durations of 9 to 10 months, and median survival of 20 to 24 months. While allogeneic stem cell transplantation (ASCT) is curative in pts with MDS, the long-term outcome of pts treated with HMA remains unknown. Aims: The aims of the study are to assess the long-term outcome of pts with MDS treated with HMA and to identify prognostic factors of long-term outcome. This may help selecting patients for this long-term treatment in whom ASCT may not be indicated. Methods: We reviewed the records of 511 pts with diagnosed MDS (n=409) and CMML (n=102) treated from 4/2000 to 4/2014 and who were treated with HMA. Pts who received ASCT (n=65) were excluded. Thus, a total of 446 pts were evaluable for the study. The probabilities of leukemia-free survival (LFS) and overall survival (OS) were estimated using the method of Kaplan and Meier. Univariate and multivariate analyses were performed to identify potential factors associated with the achievement of response with logistic regression models and survival with Cox proportional hazard regression models. Results: The median follow-up for the entire cohort was 13.6 months. Pt characteristics are outcomes described in Table 1. Best responses to HMA were CR in 124 (28%) pts, CRp in 27 (6%), PR in 9 (2%), HI in 31 (7%). Median duration of response was 7 months (1-68). 130 (29%) transformed into AML after a median of 11 months (11-60). At the last follow-up 133 (30%) remained alive. The median LFS and OS were 16.1 and 16.2 months respectively. The 2- and 5-year LFS and OS rates were 29% and 11% and 34% and 12%, respectively. By multivariate analysis, baseline characteristics associated with OS included WBC (>4 vs. ≤4), ferritin (>500 vs. ≤500), hemoglobin (>10 vs. ≤10), platelets (>500 vs. ≤500) and cytogenetics (high vs. intermediate vs. low risk) (p<0.05). Since the relative impact of each of these 5 factors on survival was similar, we assigned an arbitrary value of 1 to each of them, except for cytogenetics (0=low risk; 1=intermediate risk; and 2=high risk). Patients with 0-2 (n=265) or 3-5 (n=180) adverse factors had a median survival of 18 and 14 months, respectively (p= 0.001). To assess the benefit of achieving a response, we repeated the multivariate survival analysis using an 8-week landmark that excluded 38 patients who died within 8 weeks. The median survival was 15 months overall (8 and 20 months for patients with and without CR/CRp, PR/HI, respectively; p<0.001). The multivariate analysis included 315 patients and selected the achievement of response (CR/CRp/PR/HI vs. others), WBC (>4 vs. ≤4), ferritin (>500 vs. ≤500), platelets (>500 vs. ≤500) and cytogenetics (0=low risk; 1=intermediate risk; and 2=high risk) as independently associated with survival improvement Patients with 0-2 (n=244) or 3-5 (n=162) adverse factors had a median survival of 19 and 13 months, respectively (p<0.001). Conclusion: Our current analyses identified a small subset of pts with MDS in whom outcome of therapy with HMA is excellent and can be differentially predicted. Table 1. Patient Characteristics and Outcomes Parameter (N=446) Number (%); Median [range] Age (years) 70 (13-92) White Blood Cell Count (x 109/L) 3.5 (0.5-212) Ferritin 465.0 (0-10971) Hemoglobin (g/dL) 9.7 (6-16) Platelets (x 109/L) 68.0 (4-987) Bone marrow blasts (%) 6.0 (0-19) Prior malignancy 198 (44) Prior chemotherapy 133 (30) Prior radiotherapy 85 (19) Prior Transfusion 134 (30) Cytogenetics (by IPSS) Low 213 (48) Intermediate 78 (17.5) High 144 (8) Missing 11 (2.5) WHO RA 47 (10.5) RARS 16 (4) RCMD 75 (17) RAEB 204 (46) MDS-U 8 (2) CMML 95 (21) Missing 1 (0.2) IPSS Low 46 (10) Intermediate-1 193 (43) Intermediate-2 156 (35) High 36 (8) Missing 15 (3) MDA Score Low 59 (13) Intermediate-1 113 (25) Intermediate-2 124 (28) High 113 (25) Missing 37 (8) Type of HMA Azacitidine/ AZA+ 189 (42) Decitabine/DAC 257 (58) Response to HMA CR 124 ( 28) CRp 27 (6) PR 9 (2) HI 31 (7) NR 121 (27) Died on therapy 23 (5) NE 6 (1.4) Missing 105 (23.5) Median duration of response (mos) 7.2 (1-68) Transformed into AML 130 (29) Dead 313 (70) Disclosures No relevant conflicts of interest to declare.

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Long-term outcome of extratemporal epilepsy surgery among 154 adult patients

Journal of Neurosurgery ◽

10.3171/jns/2008/108/4/0676 ◽

2008 ◽

Vol 108 (4) ◽

pp. 676-686 ◽

Cited By ~ 58

Author(s):

Alaa Eldin Elsharkawy ◽

Friedrich Behne ◽

Falk Oppel ◽

Heinz Pannek ◽

Reinhard Schulz ◽

...

Keyword(s):

Epilepsy Surgery ◽

Cox Regression ◽

Adult Patients ◽

Class I ◽

Seizure Outcome ◽

Term Outcome ◽

Long Term Outcome ◽

Factors Associated

Object The goal of this study was to evaluate the long-term outcome of patients who underwent extratemporal epilepsy surgery and to assess preoperative prognostic factors associated with seizure outcome. Methods This retrospective study included 154 consecutive adult patients who underwent epilepsy surgery at Bethel Epilepsy Centre, Bielefeld, Germany between 1991 and 2001. Seizure outcome was categorized based on the modified Engel classification. Survival statistics were calculated using Kaplan–Meier curves, life tables, and Cox regression models to evaluate the risk factors associated with outcomes. Results Sixty-one patients (39.6%) underwent frontal resections, 68 (44.1%) had posterior cortex resections, 15 (9.7%) multilobar resections, 6 (3.9%) parietal resections, and 4 (2.6%) occipital resections. The probability of an Engel Class I outcome for the overall patient group was 55.8% (95% confidence interval [CI] 52–58% at 0.5 years), 54.5% (95% CI 50–58%) at 1 year, and 51.1% (95% CI 48–54%) at 14 years. If a patient was in Class I at 2 years postoperatively, the probability of remaining in Class I for 14 years postoperatively was 88% (95% CI 78–98%). Factors predictive of poor long-term outcome after surgery were previous surgery (p = 0.04), tonic–clonic seizures (p = 0.02), and the presence of an auditory aura (p = 0.03). Factors predictive of good long-term outcome were surgery within 5 years after onset (p = 0.015) and preoperative invasive monitoring (p = 0.002). Conclusions Extratemporal epilepsy surgery is effective according to findings on long-term follow-up. The outcome at the first 2-year follow-up visit is a reliable predictor of long-term Engel Class I postoperative outcome.

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Long-Term Outcome of Anemic Non Del 5q Lower-Risk MDS Refractory to or Relapsing After Erythropoiesis Stimulating Agents (ESAs)

Blood ◽

10.1182/blood.v116.21.442.442 ◽

2010 ◽

Vol 116 (21) ◽

pp. 442-442

Author(s):

Charikleia Kelaidi ◽

Sophie Park ◽

Rosa Sapena ◽

Odile Beyne-Rauzy ◽

Valérie Coiteux ◽

...

Keyword(s):

Multivariate Analysis ◽

Lower Risk ◽

Who Classification ◽

Initial Response ◽

Primary Resistance ◽

Term Outcome ◽

Long Term Outcome ◽

Median Serum

Abstract Abstract 442 Background. ESAs are usually the first line tx of anemia in non del 5q lower risk MDS. However, not all pts respond to ESAs and median response duration is only about 2 years (Park, Blood 2008;111:574). Long-term outcome of pts who do not respond to or relapse after response to ESAs is incompletely known. We analyzed this outcome by updating a previously reported lower-risk MDS cohort of 403 pts treated with ESA in centers of the GFM (Blood 2008;111:574). Methods. We analyzed in that cohort low and int-1 (lower risk) IPSS pts with Hb<10g/dL, requiring or not RBC transfusions, who did not respond to or relapsed after ESAs, according to IWG 2000 criteria. Pts with MPN/MDS, unclassified MDS, therapy related-MDS, del 5q or 3q, IPSS int-2/high and pts who, at the time of relapse of ESAs, had progressed to AML or higher risk MDS were excluded. Pts had started ESA tx between 1998 and 2006, and data were reanalyzed 4 years after the last pt inclusion (at the reference date of 1 July 2010). 93 pts of the cohort who responded to ESAs but had not relapsed at the end of this follow up period were used for comparisons. Results. 177 pts, including 94 with primary resistance to ESAs and 83 with relapse after an initial response were analyzed. In the 94 pts with primary resistance to ESAs, M/F was 2, median age 75, WHO classification at tx onset RA, RCMD, RARS, RAEB-1 in 17%, 27%, 28%, 27% of cases, respectively (resp), karyotype fav, intermediate (int) in 86% and 14% pts, resp, IPSS low, int-1 or assignable to low/int-1 in 35%, 60% and 5% pts, resp. Median serum ferritin was 658 ng/mL and median serum EPO level (sEPO) 125 IU/L. 63% of the pts were RBC transfusion dependent (TD) (median 2 RBC units/month). Median overall survival (OS) and 3-y cumulative incidence (CI) of AML from tx onset were 43 months (mo) and 18%, resp. Among pre-tx characteristics, age >75 was associated with shorter survival (median OS 31 mo vs. not reached for age <75, P=0.01) along with int karyotype (median 26 vs 56 mo in pts with fav karyotype, P=0.005). Using multivariate analysis, only cytogenetics maintained prognostic significance for OS. No prognostic factor of AML progression was found. 21% of the 94 pts were aged <65. Their 3-y CI of AML was 19.4% vs 7.4% in pts aged >65 (P=0.93), and their median OS was not reached vs 41 mo in pts aged >65 (P=0.03). 83 pts relapsed after an initial response (IWG 2000 major and minor in 60.2% and 39.8% pts, resp) of 16.5 mo median duration (range 3–74 mo). At tx onset, M/F was 1.35, median age 74.3, WHO classification RA, RCMD, RARS, RAEB-1 in 14%, 38%, 32%, 16% of cases, resp, karyotype fav, int in 92% and 8% pts, resp, IPSS low, int-1 in 51% and 49% of pts. Median serum ferritin was 695 ng/mL and median sEPO 64 IU/L. 45% of the pts were TD (median 2 RBC units/mo). Median OS and 3-y CI of AML after relapse were 53 mo and 9.7%, resp. Median OS after relapse was 26 mo in RAEB-1 and not reached in other WHO subtypes (P=0.06) and was not influenced by the presence of multilineage dysplasia. Pts who relapsed after 24 mo had a 4.1% 3-y CI of AML vs 12.8% in pts who relapsed before 24 mo (P=0.40). Median OS was not reached in pts who relapsed after 24 mo vs 53 mo in those relapsing before 24 mo (P=0.90). No pre-tx characteristic was predictive of relapse before or after 24 mo. 16% of the 83 pts were aged <65. Their median OS after relapse was not reached at 4 years vs also not reached in pts aged >65 (P=0.17), and their 3- CI of AML after relapse was 0% vs 12% in pts aged >65 (P=0.31). In the overall pt population (ie pts with primary resistance, pts with relapse and pts with sustained response), univariate competing risk modeling found CI of death from cardiovascular causes to be correlated with TD and older age at tx onset but not with response status, while only age remained significant in multivariate analysis (HR=1.12 [1.014-1.24], P=0.02). Both older age and early failure (ie primary failure or relapse <24 mo) were associated with increased CI of death from MDS-related causes (AML, hemorrhage, infection) (HR=1.05 [1.00-1.10], P=0.04; and HR=5.64 [1.85-17.22], P=0.002, resp). Conclusions. Failure to respond or loss of response to ESAs in the absence of frank disease progression to AML or higher risk MDS was not associated with poor outcome in lower-risk MDS, except in some pt subgroups (pts with intermediate karyotype and with a diagnosis of RAEB-1). Those figures have to be taken into account for therapeutic decisions, especially in pts aged <65 years, where median survival was not reached with relatively long term follow up. Disclosures: Off Label Use: ESAs for anemia in MDS. Fenaux:CELGENE, JANSSEN CILAG, ROCHE, AMGEN, MERCK, GSK, NOVARTIS, CEPHALON: Honoraria, Research Funding.

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Long-Term Prognosis for Jumper's Knee in Male Athletes: Prospective Follow-up Study

The American Journal of Sports Medicine ◽

10.1177/03635465020300051001 ◽

2002 ◽

Vol 30 (5) ◽

pp. 689-692 ◽

Cited By ~ 130

Author(s):

Jyrki A. Kettunen ◽

Martti Kvist ◽

Erkki Alanen ◽

Urho M. Kujala

Keyword(s):

Response Rate ◽

Jumper’S Knee ◽

Term Outcome ◽

Male Athletes ◽

Long Term Outcome ◽

Kujala Score ◽

Long Term Prognosis ◽

Knee Problem

Background: Little information is available on the long-term outcome of jumper's knee, a common problem among athletes. Purpose: Our aim was to determine the 15-year prognosis of jumper's knee. Study Design: Prospective case control. Methods: The prognosis for jumper's knee was studied using two groups: athletes with jumper's knee and nonsymptomatic control athletes. At baseline, all subjects participated in standardized clinical examinations and measurements, and 15 years later they were asked to respond to a questionnaire. Results: Twenty athletes with jumper's knee and 16 athlete control subjects responded (response rate 74% and 84%, respectively). The jumper's knee group reported significantly more knee symptoms according to their Kujala score and more knee pain after repeated squatting. Fifty-three percent of the subjects in the jumper's knee group (9 of 17) reported that they had quit their sports career because of their knee problem, compared with 7% of the control athletes (1 of 14). Patellar height was associated with knee symptoms at follow-up. Conclusion: Jumper's knee causes mild but long-lasting symptoms after an athletic career.

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Arkansas Autotransplant (AT) Experience with > 2500 Myeloma (MM) Patients: Follow-Up Extending to >15 Years.

Blood ◽

10.1182/blood.v106.11.1149.1149 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1149-1149

Author(s):

Frits van Rhee ◽

Guido Tricot ◽

Elias Anaissie ◽

Maureen Reiner ◽

Maurizio Zangari ◽

...

Keyword(s):

Cox Regression ◽

Standard Of Care ◽

Term Outcome ◽

Long Term Outcome ◽

Kaplan Meier ◽

Long Term Follow Up ◽

Previously Treated Patients ◽

The University

Abstract Background: AT’s have become the standard of care for MM. Long-term follow-up studies from large centers are critical to understand who benefits most and who should be considered for alternative treatment approaches. Patients and Methods: 2,605 MM patients receiving at least one AT at the University of Arkansas were considered for this study. Kaplan-Meier analysis was used to estimate median event-free (EFS) and overall survival (OS). Cox regression was used to evaluate independent prognostic factors of EFS and OS from AT. Results: Of the 2,605 patients, 891 were enrolled into front line Total Therapy (TT) protocols TT1/2/3 (TT); 1,012 were treated on protocols for previously treated patients (non-TT); and 702 were treated off protocol due to significant co-morbidities or patient/MD preference (non-P). Median EFS and OS for all patients are 29 mo and 51 mo; 10-yr EFS and OS are 18% and 23%; 12% survived >15yr. Features independently predicting superior survival included TT (HR 0.51, p<.001), absence of cytogenetic abnormalities (no CA) (HR 0.47, p<.001), timely application of 2nd transplant (< 6 months of 1st transplant) (HR 0.71, p<.001) as well as B2M < 3mg/L, CRP < 6mg/dL, albumin >=3g/dL, platelet count >=100.000/microL (all p<.001) and age <65yr (p=.008). The figure depicts survival (landmarked at 6 months after 1st transplant) according to the number of favorable features present of the 5 strongest predictors (TT, 2 transplants within 6 months, no CA, low B2M, low CRP). Conclusion: This large single institution experience demonstrates that > 10yr survival can be accomplished in over one-half of the patients presenting without CA (14%), with low levels of B2M and CRP and receiving TT and timely 2nd autotransplant. The worst constellation affected 5% of all patients presenting with at most 1 good-risk feature whose 5-yr survival was only 8%. Collectively, these data should serve as a standard for MM investigators and patients alike, against which long-term outcome of newer treatments should be measured. Figure Figure

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Allogeneic Hematopoietic Cell Transplantation (HCT) for Advanced Mycosis Fungoides and Sezary Syndrome (MF/SS): Impact of Increasing the Use of Unrelated Donors (UD) - the EBMT Lymphoma Working Party Experience

Blood ◽

10.1182/blood.v126.23.4403.4403 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4403-4403

Author(s):

Rafael F. Duarte ◽

Ariane Boumendil ◽

Francesco Onida ◽

Herve Finel ◽

Ian H Gabriel ◽

...

Keyword(s):

Multivariate Analysis ◽

Univariate Analysis ◽

Stage Iv ◽

Working Party ◽

Independent Effect ◽

Independent Factor ◽

Long Term Outcome ◽

Allogeneic Hct

Abstract Introduction: The EBMT Lymphoma Working Party has previously reported on the long-term outcome of allogeneic HCT for patients with advanced MF/SS [J Clin Oncol 2014; 32: 3347-8 ]. Among a number of disease and transplant factors influencing patient outcome, the use of UD showed to be the strongest independent factor influencing overall survival (OS). The main shortcoming of the original reports was a limited number of 60 cases in the series, of which only 15 received allogeneic HCT from UD. As UD have been increasingly used during recent years, we sought to extend our previous analysis (1997-2007) to include patients with MF/SS allografted between 2008-2011. Patient and Methods: Endpoints were OS, progression-free survival (PFS), non-relapse mortality (NRM) and incidence of disease relapse/progression (DRP). Eligible were patients >= 18 years who were registered with the EBMT and had received an allogeneic HCT for MF/SS between 1997-2011. Centers with eligible patients were contacted to provide additional treatment and follow-up information including a written diagnostic report. Data were collected from the EBMT Registry (closed in July 2014), and endpoints were defined and analyses performed according to EBMT statistical guidelines (www.ebmt.org). Results: Eligible for final analysis were a total of 113 patients, including our original 60 cases (1997-2007) and 53 new cases (2008-2011): 71 men and 42 women, median age at HCT 48 years (21-72), 77 MF (68%) and 36 SS (32%), with 7 EORTC/ISCL stage IIB, 17 stage III, 46 stage IV-A and 26 stage IV-B (17 missing). Demographics of both time periods were comparable, except for a marked increase in the use of UD (15/60, 25% vs 29/53, 55%; p=0.001) and a reduction in the use of TBI for conditioning (30/60, 50% vs 15/53, 28%; p=0.031) in recent years. At HCT, 52 patients (46%) were refractory or in relapse/progression and 61 (54%) in complete or partial remission. Eighty-six patients (76%) received reduced-intensity (RIC) and 27 (24%) myeloablative (MAC) conditioning regimens, including TBI in 45 cases (40%). With a median follow up in survivors of 72 months (IQR: 39-97), allogeneic HCT for MF/SS offers an estimated OS of 56% at 1 year, 44% at 3 years and 38% at 5 years, and PFS of 34% at 1 year, 28% at 3 years and 25% at 5 years. NRM was 26% at 1 year and 28% at 3 years and thereafter. DRP was the main cause of treatment failure, with a probability of 40% at 1 year, 44% at 3 years and 47% at 5 years, and a mortality rate after DRP of 70% (35/50). It is worth noting that 15 patients (30%) remain alive at last follow up despite DRP, suggesting that some of these patients can be successfully rescued with donor lymphocyte infusions and other therapeutic interventions. The cumulative incidence of acute GVHD was 47% at day 100, and chronic GVHD 35% at 1 year, 45% at 3 years and 48% at 5 years. Interestingly, the univariate analysis showed a statistical trend towards a poorer OS in the cohort of new cases registered from 2008 (p=0.106). However, transplant period had no significant impact when included as a covariate in multivariate analysis, and appears to associate with the higher percentage of UD transplants in the new cohort. The use UD remained the main negative independent factor for OS (HR: 0.490; 95CI: 0.283-0.848; p=0.011) and PFS (HR: 0.468; 95CI: 0.259-0.843; p=0.011) in the multivariate models unstratified and stratified by inclusion period. The use of TBI in conditioning appears to have an independent effect to reduce the risk of DRP in the multivariate analysis (HR: 0.427; 95CI: 0.199-0.917; p=0.029), but does not translate into OS or PFS. Conclusions: This extended series confirms the existence of a clinically relevant graft-versus-lymphoma effect in MF/SS, permitting long-term disease control in a substantial proportion of high-risk patients. Follow-up studies need to address the still significant adverse effect of UD and the role of TBI conditioning in order to improve HCT results in these otherwise fatal disorders. Disclosures Mufti: Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.

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Long-Term Outcome after Immunosuppressive Therapy with Rabbit ΑΤG for Pediatric Aplastic Anemia: A Single-Center Retrospective Study in China

Blood ◽

10.1182/blood.v128.22.2678.2678 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2678-2678

Author(s):

Jingliao Zhang ◽

Lixian Chang ◽

Ye Guo ◽

Yingchi Zhang ◽

Tianfeng Liu ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Response Rate ◽

First Line ◽

Term Outcome ◽

Long Term Outcome ◽

Free Survival ◽

Time Points

Abstract Background: Antithymocyte globulin (ATG)-based immunosuppressive therapy (IST) has been successfully used as the first-line treatment for severe / very severe aplastic anemia (SAA/VSAA) patients if no HLA-matched sibling donor was eligible for HSCT as a first choice. It was reported rabbit ATG (rATG) produced more profound immunosuppressive activity compared to horse ATG (hATG). However, recent clinical studies indicated that the stronger lympholytic activity did not mean that rATG was more effective. Most experiences from adult SAA/VSAA implied the efficacy of rATG was worse than hATG. However, susceptibility of children to intensive IST might not be exactly the same as adult patients, long-term efficacy of rATG in historic studies for children with SAA/VSAA was still elusive. Purpose: This study includes the largest cohort of pediatric AA patients treated with first-line rATG+CSA regimen published to date after a median follow-up of 69 months, aiming to assess the long-term outcome of rATG for children, and to identify the significant prior factors in clinical decision making. Methods: We reviewed 231 SAA/VSAA patients under 18 years old assigned to rATG+CSA from February 2000 to May 2014 in Department of Pediatrics, the Blood Diseases Hospital & Institute of Hematology, CAMS & PUMC. Response was evaluated 3, 6, 9, 12 24, 36 and 60 months after IST. We separately defined SAA-II as a specific type of gradually progressed SAA from a NSAA status within a longer period for at least 6 months. Multivariate logistic regression models were used to evaluate the effects of variables on the responses at different time points. Multivariate Cox model analysis of overall survival (OS) and failure-free survival (FFS) was calculated for variables with a log rank P value less than 0.1 in Kaplan-Meier analysis. Results: Of the overall patients, the total responded patients were 79(34.3%), 110(51.6%), and 129 (60.6%) at 6, 9, 12 months following IST, respectively. Intriguingly, 22 patients achieved delayed response between 12 months and 24months after IST, which increased the overall response rate by 10.2%, afterwards the rate reached a plateau by 3 years with the best response rate of 74.6% (Figure 1). Differences in baseline clinical parameters pre-IST were associated with response to IST. Absolute neutrophil count (ANC) less than 0.1*109/L was associated with an unfavorable early response rate at 6 months (P=0.009); absolute lymphocyte count (ALC) less than 1.6*109/L was a significant predictor for better response by 6 months and 12 months in multivariate analysis [6 months, P=0.033 vs. 12 months, P=0.021]. Lower absolute reticulocyte count (ARC no more than 18.5*109/L) predicted worse late IST response by 2 years and 3 years. In our large series of cohort, 5-year OS and FFS were 82.7% and 61.9%. Patients with VSAA as a significantly unfavorable prognostic factor had a much lower probability of 5-year survival when compared to patients diagnosed with SAA (76.4% vs. 87.2%, P<0.001, Figure2A). In multivariate analysis, SAA-II (P=0.021, Figure2B), and a pretreatment lower ARC (P=0.020, Figure2C) were independent unfavorable prognostic factors for FFS, but moderate PNH clone size (more than 5%) was verified as a good predictor for FFS (P=0.006, Figure 2D). At the last follow-up, twelve of the 135 responders relapsed after IST, meanwhile eight patients in responders and seven patients in non-responders experienced clonal evolution after IST, corresponding to cumulative incidences at 5.2% of relapse and 6.5% of evolution, which were obviously lower than previous reports. Conclusions: The combination of rATG and CSA was confirmed as an effective first-line therapy for children with SAA/VSAA in our cohort. We discerned a protracted recovery but an ultimately comparable long-term outcome of rATG. Baseline blood parameters (ANC, ALC, ARC) were predictive factors of response rate. Intensive supportive care may be necessarily pivotal to survival in cases of VSAA. Importantly, moderate PNH clone might be beneficial to FFS. Besides, for those who experienced gradually progressed disease course, early HSCT might be a more preferable option than receiving IST although further validation remains to be done. Figure 1 Overall efficacy at different time points following IST initiation Figure 1. Overall efficacy at different time points following IST initiation Figure 2 Prognostic factors for overall survival (OS) and failure-free survival (FFS) Figure 2. Prognostic factors for overall survival (OS) and failure-free survival (FFS) Disclosures No relevant conflicts of interest to declare.

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Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

10.1101/630525 ◽

2019 ◽

Author(s):

Maria Stangou ◽

Smaragdi Marinaki ◽

Evangelos Papachristou ◽

Chrysanthi Kolovou ◽

Erasmia Sambani ◽

...

Keyword(s):

Membranous Nephropathy ◽

Response Rate ◽

Calcineurin Inhibitors ◽

Term Outcome ◽

Long Term Outcome ◽

Group I ◽

Frequent Relapses ◽

Long Term Follow Up

AbstractManagement of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up.Aimof the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN.Patients-MethodsClinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens.ResultsTwenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87)yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n=381) compared to those initially treated with Cyclo (n=110), relapse rate: 25.2% vs. 6.4%, p<0.0001, and no response rate: 22.5% vs. 13.6%, p=0.04, respectively.ConclusionsLong term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

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Long-term outcome after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer and predictive factors for a pathologic complete remission: Results of a multivariate analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.27_suppl.154 ◽

2012 ◽

Vol 30 (27_suppl) ◽

pp. 154-154

Author(s):

Christiane Matuschek ◽

Edwin Boelke ◽

Hans Bojar ◽

Stephan L. Roth ◽

Matthias Peiper ◽

...

Keyword(s):

Breast Cancer ◽

Multivariate Analysis ◽

Locally Advanced ◽

Breast Conservation ◽

Time Interval ◽

Term Outcome ◽

Term Survival ◽

Long Term Outcome

154 Background: An earlier published series of neoadjuvant radio-chemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (PCR) were analyzed. Methods: 315 LABC patients (cT1-cT4 /cN0-N1) were treated during 1991-1998 with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or—in case of breast conservation—a 10-Gy interstitial boost with 192Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX and the time interval between end of RT and surgery were examined in multivariate terms with as endpoint pCR and overall survival. Results: The total PCR rate after neoadjuvant RT-CHX reached 29.2 % with LABC breast conservation becoming possible in 50.8%. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1,17 [95% CI 1,05-1,31], p<0,01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80 to 0.99], p = 0.03) could be obtained. Importantly, a pCR was the strongest prognostic factor for long-term survival (HR 0.28 [95% CI 0.19-0.56], p<0.001). Conclusions: A PCR identifies patients with a significant better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of a pCR after NRT-CHX.

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Spectrum and Outcome of Noninfectious Aortitis

The Journal of Rheumatology ◽

10.3899/jrheum.201274 ◽

2021 ◽

pp. jrheum.201274

Author(s):

Yasmina Ferfar ◽

Sarah Morinet ◽

Olivier Espitia ◽

Christian Agard ◽

Mathieu Vautier ◽

...

Keyword(s):

Multivariate Analysis ◽

Inflammatory Diseases ◽

Vascular Complications ◽

Relapsing Polychondritis ◽

Term Outcome ◽

Long Term Outcome ◽

Igg4 Related Disease ◽

Cogan Syndrome

Objective To assess the spectrum and long-term outcome of patients with noninfectious aortitis. Methods We performed a retrospective multicenter study of 353 patients (median age at diagnosis was 62 [IQR 46–71] yrs and 242 [68.6%] patients were women) with noninfectious aortitis. Factors associated with vascular complications were assessed in multivariate analysis. Results We included 136 patients with giant cell arteritis (GCA), 96 with Takayasu arteritis (TA), 73 with clinically isolated aortitis (CIA), and 48 with aortitis secondary to inflammatory diseases (including Behçet disease, relapsing polychondritis, IgG4-related disease, Cogan syndrome, ankylosing spondylitis). After a median follow-up of 52 months, vascular complications were observed in 32.3%, revascularizations in 30% of patients, and death in 7.6%. The 5-year cumulative incidence of vascular complications was 58% (95% CI 41–71), 20% (95% CI 13–29), and 19% (95% CI 11–28) in CIA, GCA, and TA, respectively. In multivariate analysis, male sex (HR 2.10, 95% CI 1.45–3.05, P < 0.0001) and CIA (HR 1.76, 95% CI 1.11–2.81, P = 0.02) were independently associated with vascular complications. Conclusion Noninfectious aortitis accounts for significant morbidity and mortality. CIA seems to carry the highest rate of vascular complications.

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