scholarly journals Updating Long-Term Outcome of Intermittent Imatinib (INTERIM) Treatment in Elderly Patients with Ph+-CML

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1794-1794 ◽  
Author(s):  
Domenico Russo ◽  
Giovanni Martinelli ◽  
Michele Malagola ◽  
Valeria Cancelli ◽  
Cristina Skert ◽  
...  
Keyword(s):  
Research Funding ◽  
Chromosomal Abnormalities ◽  
Residual Disease ◽  
Chronic Obstructive ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Term Outcome ◽  
Long Term Outcome

Abstract BACKGROUND: The INTERIM study (ClinicalTrials.gov NCT 00858806) showed that in elderly (> 65 years) Ph+ CML patients selected for a stable complete cytogenetic response (CCgR) lasting > 2 years, the policy of intermittent imatinib treatment (one month on/one month off) may affect the markers of residual disease (CCgR and major molecular response, MMR or MR3.0), but not the clinical outcomes (overall survival and progression-free survival) (Russo D et al, Blood 2013; 121(26):5138-44). AIMS: To update the results of the INTERIM Study, with a follow up ≥ 5 years. METHODS: After 4 years of follow up, patients continouing INTERIM treatment were monitored with peripheral blood RT-Q-PCR every 3 months according to the ELN-2013 guidelines. RESULTS: At 48thmonth, out of 76 patients enrolled in the INTERIM study, 13 (17%) had lost CCgR and MMR, 14 (18%) had lost MMR only and 50 patients (75%) continued INTERIM. The patients who had lost CCgR and/or MMR resumed imatinib continuously and all of them regained the CCgR and the MMR, within 3 to 12 months. No patient progressed to accelerated or blastic phase, or developed clonal chromosomal abnormalities in Ph+ cells, or BCR-ABL mutations. No patient complained of new or more severe side effects during the months “on”. After a follow up ≥ 5 years, 45/76 (59%) enrolled patients are on INTERIM, with a probability of maintaining intermittent administration of 59% (95% CI: 46-69). No patient lost the CCgR and only 9 additional patients lost the MMR while on intermittent treatment. All these patients resumed continuous imatinib treatment and regained the MMR. Thus, at ≥ 5 years, the probability of maintaing CCgR is 80% (95% CI 68-87) and the probability of maintaining the MMR is 61% (95% CI: 48-71). From start of INTERIM, 6 patients died but no deaths were related to CML progression (3 cases of other non haematological neoplasms, 1 stroke, 1 myocardial infarction, 1 chronic obstructive pulmonary disease).The PFS at ≥ 5 years is 94% (95% CI: 89-100) CONCLUSIONS: In summary, with a follow up ≥ 5 years, intermittent imatinib administration (INTERIM) confirmed to be safe, to produce a reversible increase of residual molecular disease in about one third of patients, but not to affect the long-term outcome. Aknowledgments: This work was supported in part by EuropeanLeukemiaNet (contract LSHC-CT-2004-503216) through the European Treatment and Outcome Study (EUTOS), supported by Novartis Oncology Europe, and COFIN 2009 Disclosures Russo: Celgene: Research Funding; Gilead: Research Funding; Novartis: Consultancy. Martinelli:Novartis: Speakers Bureau; Bristol-Meyers and Squibb: Speakers Bureau; Pfizer: Speakers Bureau. Soverini:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria; Ariad: Consultancy, Speakers Bureau. Turri:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria. Castagnetti:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria. Breccia:novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy. Abruzzese:Novartis: Consultancy. Tiribelli:Novartis: Consultancy, Honoraria; Bristol-Meyers and Squibb: Consultancy, Honoraria. Rosti:Consultant: Consultancy, Speakers Bureau; Bristol-Meiers Squibb: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau.

scholarly journals Frequency and Impact of Molecular Response’s with Nilotinib (Tasigna) in Patients (Pts) with Newly Diagnosed Philadelphia Chromosome (Ph)-Positive Chronic Myelogenous Leukemia in Early Chronic Phase (CML-CP)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3156-3156
Author(s):  
Naval Daver ◽  
Hagop M. Kantarjian ◽  
Susan O'Brien ◽  
Elias Jabbour ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Research Funding ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Landmark Analysis ◽  
Intent To Treat ◽  
Dose Reductions

Abstract Background: Nilotinib is a BCR-ABL tyrosine kinase inhibitor with approximately 50-fold higher inhibitory activity than imatinib in preclinical studies. Aim: We initiated a phase II study (in 2005) to evaluate the efficacy of frontline nilotinib in pts with newly diagnosed CML-CP. The primary objective of this report was to estimate major molecular response (MMR) and complete molecular response (CMR: minimum 100,000 ABL copies) rates with prolonged follow-up, and the impact of MMR and CMR on long-term outcome. Methods: Pts with Ph-positive or BCR-positive CML in early CML-CP [i.e., time from diagnosis 12 months] with <1 month of prior interferon-alpha and/or imatinib were eligible. Nilotinib was initiated at a dose of 400 mg twice daily. Results for CCyR and MMR are reported as intent-to-treat unless specifically annotated as response among evaluable pts (eval). Results: 140 pts have been treated as of August 1, 2014. Herein we focus on the initial 109 pts who have a minimum follow-up of 12 months. The median (med) follow-up for these 109 pts is 52.2 months (range, 0.9 to 108.0+). The med age was 50 years (range, 17 to 86). 73% of pts had Sokal low risk. 17 (16%) had received imatinib for <1 months (med 18 days; range, 5 to 29 days). Overall, 92% (100/109) pts achieved a complete cytogenetic response [CCyR] with a med time to CCyR of 2.9 months (range, 2.1 to 8.1+). The rates of CCyR at 3, 6, 12 and 18 months were 80% (eval:83%), 86% (eval:95%), 83% (eval:99%), and 77% (eval:100%), respectively. Overall, MMR and CMR were achieved in 90% (98/109) and 45% (49/109) of the pts. Med time to MMR and CMR was 3.3 months (range, 2.4 to 48.0+) and 23.1 months (range, 3.2 to 86.0+), respectively. BCR-ABL/ABL at 3 months was <10% in 94% (eval:100%) and <1% in 89% (eval: 94%). BCR-ABL/ABL at 6 months was <1% in 81% (eval:89%) and <0.1% in 65% (eval:72%) in pts evaluated at these time points. MMR was observed in 65% (eval:72%) at 6 months, 71% (eval:87%) at 12 months, and 70% (eval:90%) at 18 months. CMR was observed in 9% (eval:11%) at 6 months, 14% (eval:17%) at 12 months, and 15% (eval:19%) at 18 months. We further analyzed the association between CCyR and molecular response (Table 1). For example, among the 84 pts who were in CCyR at 18 months: MMR was achieved in 90% of these pts including MR3 in 31%, MR4 in 13%, MR4.5 in 27%, and CMR in 19%. Estimated 3-year and 5-year overall survival (OS) is 98% and 91%, respectively. Estimated 3-year and 5-year failure-free survival (FFS) is 82% and 73%, respectively. On an intent-to-treat analysis the FFS among pts who achieved CMR was superior to those who did not achieve CMR (P<0.001, respectively). On a landmark analysis, which included only those pts who received nilotinib for a minimum of 24 months (med time to CMR among pts who achieved CMR=23.1 months) the FFS among pts who achieved CMR was superior to those who did not achieve CMR (P=0.008) (Figure 1). Dose-reductions were performed in 41 (38%) pts: 30 pts required 1 dose-reduction and 11 pts required 2 or more dose-reductions. The most frequent reasons for dose-reductions included increased liver enzymes (n=8), rash (n=5), pain/arthralgia (n=4), cardiac and QTc (n=4), fatigue (n=5), and neutropenia (n=2). The actual med dose remains 800 mg daily. 29 (27%) pts are off study due to toxicity in 8 (cardiac=3, liver enzymes=4, fatigue=1), inadequate response in 5 (3 never achieved adequate and 2 lost adequate response), progression to blast-phase in 3, death in 5 (all 5 non-CML related causes), 8 due to pt choice (financial=1, non-compliance=3, pt choice=1) Conclusion: Nilotinib 400 mg twice daily is very effective. The cumulative rates of CCyR, MMR and CMR were 92%, 90%, and 45%, respectively. CMR rates continue to improve with long-term follow-up. Attainment of CMR is associated with improved long-term outcome. Table 1: Molecular response rates among pts who achieve CCyR CCyR MR3 but not MR4 MR4 but not MR4.5 MR4.5 but not CMR CMR No MMR 3 months 87/105 (83%) 39/87 (45%) 5/87 (6%) 8/87 (9%) 2/87 (2%) 33/87 (38%) 6 months 94/99 (88%) 35/94 (38%) 6/94 (6%) 20/94 (21%) 10/94 (11%) 23/94 (24%) 12 months 90/91 (99%) 38/90 (42%) 3/90 (3%) 23/90 (26%) 15/90 (17%) 11/90 (12%) 18 months 84/84 (100%) 26/84 (31%) 11/84 (13%) 23/84 (27%) 16/84 (19%) 8/84 (10%) PCyr, partial cytogenetic response; Min, mimimal; Inev, inevaluable; IM, insufficient metaphase Figure 1: FFS CMR versus no CMR by landmark analysis for pts who received at least 24.0 months of nilotinib Figure 1:. FFS CMR versus no CMR by landmark analysis for pts who received at least 24.0 months of nilotinib Disclosures Daver: Novartis: Research Funding. Jabbour:Novartis: Advisory board membership Other, Research Funding. Cortes:Novartis: Advisory Board membership Other, Research Funding.

Kinetics of Molecular Response with Different Tyrosine Kinase Inhibitors (TKI) Used As Frontline Therapy in Chronic Myeloid Leukemia-Chronic Phase (CML CP),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3784-3784 ◽  
Author(s):  
Kiran Naqvi ◽  
Hagop M Kantarjian ◽  
Rajyalakshmi Luthra ◽  
Elias Jabbour ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Research Funding ◽  
Transcript Level ◽  
Initial Therapy ◽  
Molecular Response ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Molecular Responses ◽  
Transcript Levels ◽  
Frontline Therapy

Abstract Abstract 3784 Background: TKI are standard therapy for patients with CML CP. Imatinib was first established as frontline therapy and more recently dasatinib and nilotinib have shown improved rates and speed of response. Early molecular response has been associated with improved long-term outcome (Blood 2009; 113: 6315), thus the kinetics and rates of molecular response are important predictors of long-term outcome. Aim: To determine the kinetics and rates of molecular response with different TKIs used as initial therapy for patients with CML CP. Methods: We evaluated all pts treated with frontline TKIs (imatinib standard dose or high dose, dasatinib and nilotinib) in consecutive or parallel trials. Cytogenetic and molecular responses were assessed at least every 3 months for the first 12 months, then every 6 months, and were defined using the recommendations of European LeukemiaNet. Molecular responses were defined using international scale. Survival was calculated by the Kaplan-Meier method. Results: Of the 485 pts treated, 73 received imatinib 400mg; 208 imatinib 800mg; 99 dasatinib, and 105 nilotinib. Median age was 48 years (15–86) and median time from diagnosis to TKI therapy was 1 mo (1–13). The median follow-up for each group were 109 months (mo) with imatinib 400, 69 mo with imatinib 800, 30 with dasatinib and 25 mo with nilotinib. Nineteen pts with clonal evolution, but otherwise in CP, were included. Sokal risk score was high in 7%, intermediate in 24% and low in 69%. Cumulative rates of complete cytogenetic response (CCyR) were: imatinib 400mg 87%; imatinib 800mg 91%; dasatinib 96%; and nilotinib 94%. The rate of MMR with imatinib 400mg was 73%, with imatinib 800mg 87%, dasatinib 86%, and nilotinib 88%. Rates of CMR (BCR-ABL/ABL ≤0.0032% IS) were 51%, 71%, 61% and 62%. Median time to achieve MMR and CMR were: imatinib 400mg, 12 mo (3–60) and 18 mo (3–60); imatinib 800mg, 6 mo (3–60) and 9 mo (3–60); dasatinib, 6 mo (3–36) and 12 mo (3–54), and nilotinib 6 mo (3–48) and 6 mo (3–42). The median transcript levels at 3, 6, 12, 18, 24 and 36 mo by treatment arm are shown in table 1. The rates of MMR and CMR at 36 mo for imatinib 400mg were 58% and 34%. Corresponding rates for imatinib 800mg were 87% and 59%; for dasatinib 87% and 54%; and for nilotinib 90% and 63%. We then assessed the probability of achieving MMR and CMR at 12 mo according to the BCR-ABL/ABL levels at earlier timepoints. Two of 9 (22%) evaluable pts with transcript level >10 at 3 mo achieved a MMR at 12 mo but none achieved a CMR. In contrast, 31/52 (60%) evaluable pts with transcript level >1–10 at 3 mo, achieved a MMR at 12 mo and 4 (8%) achieved a CMR. Similarly, pts with level >0.1–1 at 3 mo, 72/129 (56%) evaluable pts achieved a MMR and 29 pts (22%) a CMR at 12 months. For each individual TKI, a similar trend was noted where a higher transcript level (>10; >1–10; >0.1–1) at 3 mo was associated with a decline in achieving a MMR and CMR at 12 mo (MMR- imatinib 400mg: 0%; 50%; 67%, imatinib 800mg: 0%; 62%; 80%, dasatinib: 33%; 67%; 71%, nilotinib: 100%; 50%, 88%, CMR-imatinib 400mg: 0%, imatinib 800mg: 0%; 8%; 10%, dasatinib:0%; 17%; 29%, nilotinib: 0%; 0%; 32%). The probability of transformation to AP/BP by transcript levels at 3 mo (>10; >1–10; >0.1–1, ≤0.1) was 0%, 3%, 2% and 1% for the overall population, with similar trends for the different therapies. Conclusion: New TKI provide a faster improvement in molecular response among pts with CML CP receiving TKI as initial therapy. Early responses are equally predictive of long-term outcome across all treatment options. Disclosures: Kantarjian: Novartis: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Research Funding. Ravandi:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria. Cortes:BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; ChemGenex: ChemGenex is now Cephalon, Inc., Consultancy, Research Funding; Deciphera: Research Funding.

scholarly journals Long-Term Outcome of Patients with Marginal Zone Non-Hodgkin Lymphoma (MZL) Treated with Yttrium-90 Ibritumomab Tiuxetan: The Mayo Clinic Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1544-1544
Author(s):  
Muhamad Alhaj Moustafa ◽  
Ricardo Parrondo ◽  
Gregory Wiseman ◽  
Jennifer Peterson ◽  
Thomas E. Witzig ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Grade 3 ◽  
Yttrium 90

Background MZL is a low-grade non-Hodgkin's lymphoma (NHL) which involves lymph nodes, extranodal sites, or spleen. It is sensitive to radiation therapy, which is used in localized disease with curative intent. Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) that targets CD20. It is approved for relapsed/refractory low grade and follicular NHL. The data on its use in MZL is limited. We present long-term outcome of the largest reported cohort of MZL patients who received (90)Y-IT. Methods Medical records of patients who received treatment with (90)Y-IT at Mayo Clinic Cancer Center between January 2004 and December 2018 were analyzed. We selected patients with MZL and reviewed clinical data including age, gender, MZL type, clinical stage (Ann Arbor Staging System), treatment response, (90)Y-IT related adverse effects (AEs), as well as lymphoma and treatment related events. All patients received (90)Y-IT according to the standard treatment guidelines. Overall response rate (ORR) and complete response rate (CR) were calculated. Progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS) were analyzed using the Kaplan-Meier method. Results Twenty-one patients were identified (Table 1). The median age at diagnosis was 60 years (range, 11-81) and 71% (15/21) were female. 52% (11/21) were previously-untreated (UMZL) while 48% (10/21) were relapsed (RMZL). The median number of pretreatments in RMZL patients was 2 (range, 1-3). ECOG performance status at the time of treatment was 0 in 90% (19/21) and 1 in 10% (2/21). 62% (13/21) were stage III/IV disease at the time of (90)Y-IT therapy. The median follow-up was 8.5 years (95% CI; 4.5, 12.4); 17 (81%) patients remain alive. The ORR was 91% (19/21) with the two non-responders being in the RMZL group. The CR rate was 81% (17/21) and 65% (11/17) remain in CR at a median follow-up of 5.7 years (95% CI; 1.4, 11). Nine (43%) patients had a relapse during the study period. More relapses occurred in the RMZL group (7/10; 70%) compared to (2/11; 18%) in the UMZL group. Median PFS (whole cohort) was 10 years (95% CI; 2.1, NR) and TTNT (whole cohort) was not reached (NR) (95% CI; 2.1 years, NR). Median PFS was significantly higher in UMZL group compared to RMZL group NR (95% CI; 2.5 years, NR) vs 2.1 years (95% CI; 0.17, 9.9), respectively (Figure 1-A).Median OS (whole cohort) was 19.3 years (95% CI; 8.9, 19.3) without statistical difference in between UMZL group and RMZL group NR (95% CI; NR, NR) vs 16.6 years (95% CI; 9, 19.4), respectively (Figure 1-B). None of the 11 UMZL patients died at median follow up of 4.7 years (95% CI; 1.6, 9.2). All 4 deaths were in the RMZL group with 3 dying of transformation to high-grade lymphoma at 8, 22, and 25 months post-(90)Y-IT treatment. One patient died of myelodysplastic syndrome 7.3 years post-(90)Y-IT treatment while in CR. Toxicities were primarily hematologic. Grade ³3 neutropenia was observed in 6/21 (29%) patients with median time to nadir of 48.5 days (range, 19-70) and median time to recovery to normal absolute neutrophil count of 39.5 days (range, 7-476). Grade ³3 thrombocytopenia was observed in 3 (14%) patients with median time to nadir of 35 days (range, 19-357) and median time to recovery of 21 days (range, 2-538). Grade ³3 anemia was observed in only one patient. Only two patients required transfusions and growth factor support. Non-hematologic AEs included mild to severe fatigue in 4 patients. Conclusion RIC with (90)Y-IT is efficacious and well-tolerated in patients with previously untreated as well as relapsed MZL. As expected it appears to be more efficacious in previously untreated patients. Long-term complete remission (&gt;5 years) was observed in 52% of the study population (43% of UMZL and 9% of RMZL). Combination of efficacy, tolerability, and treatment schedule most convenient for patients makes (90)Y-IT a reasonable alternative to systemic therapy with immunotherapy, chemotherapy, or chemo-immunotherapy in management of MZL. Figure 1: (A) Progression-free survival; comparing time to progression or death after (90)Y-IT treatment between previously untreated patients (UMZL) and patients with relapsed MZL (RMZL), (B) Overall survival; comparing time to death from all causes after (90)Y-IT treatment between UMZL patients and RMZL patients. Disclosures Tun: Curis: Research Funding; TG Therapeutics: Research Funding; BMS: Research Funding; DTRM Biopharma: Research Funding; Celgene: Research Funding; Mundi-pharma: Research Funding. OffLabel Disclosure: The use of Yttrium-90 ibritumomab tiuxetan as a first line treatment for marginal zone lymphoma

Perinatal and long-term outcome (up to 24 months) with isolated ventriculomegaly

2019 ◽  
Author(s):  
S.I. Buryakova, R.S. Bataeva
Keyword(s):  
Chromosomal Abnormalities ◽  
Perinatal Outcomes ◽  
Postnatal Period ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Lateral Ventricles ◽  
Retrospective Assessment ◽  
Parent Counseling

A retrospective assessment of the pregnancy outcome, ultrasound data, childbirth outcome and neurological postnatal follow-up was carried out for 62 cases of isolated enlargements of the occipital horns of the lateral ventricles revealed prenatally. It was found that the incidence of unfavourable perinatal outcomes in newborns with isolated pre-ventriculomegaly (3.8 %) and borderline ventriculomegaly (10 %) revealed in the antenatal period (10 %) did not exceed that one in newborns with normal width of the occipital horns of the lateral ventricles (7.9 %). There were no unfavourable outcomes at the age up to 24 months in these groups. Unfavourable perinatal outcomes (neurological disorders, chromosomal abnormalities and pathology revealed postnatally by MRI) occurred in 66.6 % of cases with “apparently” isolated moderate ventriculomegaly and long-term unfavourable outcomes were observed in half of the cases. If isolated moderate ventriculomegaly are revealed, invasive prenatal diagnosis, MRI and parent counseling about the neurological risks in the postnatal period are necessary.

Disease Patterns for Patients (pts) with Chronic Myeloid Leukemia (CML) That Have BCR-ABL Transcript Levels > 10% At 3 Month of Therapy with Tyrosine Kinase Inhibitors (TKIs)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3757-3757
Author(s):  
Aziz Nazha ◽  
Hagop M. Kantarjian ◽  
Preetesh Jain ◽  
Elias J. Jabbour ◽  
Alfonso Quintás-Cardama ◽  
...  
Keyword(s):  
Research Funding ◽  
Strong Predictor ◽  
Chronic Phase ◽  
Transcript Level ◽  
Initial Therapy ◽  
Molecular Response ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival

Abstract Abstract 3757 Background: Response to TKIs in CML at 3 month is a strong predictor for long term outcome in CML patients treated with TKIs. Pts who do not achieve a BCR-ABL transcript level < 10% or a MCyR at 3 months have lower event-free survival (EFS) and perhaps overall survival (OS). However, pts have rarely changed therapy based on response at this early time points. The purpose of this analysis is to understand the patterns of disease progression and management in this group of patients. Patients and Methods: A total of 489 newly diagnosed CML pts that received initial treatment with TKIs: imatinib 400 mg daily (83) imatinib 800 mg daily (199), and second generation TKIs (2GTKIs) (207) in consecutive or parallel trials between 7/2000 and 6/2011 were included in this analysis. Cytogentic and molecular responses were evaluated every 3 month for the first year and then every 6 month. Event was defined as transformation to accelerated phase (AP) or blast phase (BP), loss of complete hematologic response (CHR), or loss of MCyR. Results: Among the 489 treated pts, 58 (12%) did not achieve a MCyR or BCR-ABL transcript level < 10 % at 3 months (26 pts (31%) received IM400, 19 (10%) IM800, and 13 (6%) 2GTKIs. Eleven of these pts (19%) had high sokal score at diagnosis (1 pt treated with imatinib 400, 7 with imatinib 800, 3 with 2GTKIs). By 6 months, 52/58 pts (90%) continued on their original therapy: 39 (67%) at the same dose and 19 (33%) with a decreased dose because of adverse events. No pt had a dose increase. Six pts had discontinued therapy by 6 month: 4 due to intolerance, 1 loss of CHR and 1 for progression to BP. At 6 month, 27 pts (47%) achieved MCyR or BCR-ABL transcript level < 10 %. At 12 months, 47 pts (81%) were still receiving their initial therapy, 11 pts (19%) had discontinued their initial TKI: 6 due to intolerance, 1 loss of CHR, 2 for progression to BP, and 2 for resistant disease. After a median follow up of 95 months, 17 pts (29%) continue to receive their initial therapy and their current disease status are: complete cytogenetic response (CCyR) in 14 (82%), 2 (12%) lost their CCyR, and 1(6%) pt who never achieve any cytogenetic or molecular response and remains in chronic phase on the same dose of imatinib for over 8 years. Among these 17 pts, 11 (65%) have MMR, 2 (12%) with MR4.5, and 4 (24%) have lost MMR (2 of them with loss of CCyR). The 5 years OS, EFS and transformation-free survival (TFS) for the patients who did not achieve any response at 3 month was 88%, 77%, and 94%, respectively. The OS, EFS, and TFS for the patients who subsequently achieved a response (MCyR or BCR-ABL transcript level < 10 %) at 6 month was 100%, 66%, and 95%, respectively vs those who continued to have no response 79%, 95%, and 100%, respectively (P = 0.17, 0.07, 0.99, respectively). Conclusions: Although BCR-ABL transcript level at 3 month may predict long-term outcome of pts with CML treated with TKIs, this represents a static, one-time measure. Assessing the response at 6 months of pts with poor response at 3 months may provide a better predictor of long term outcome. Disclosures: Cortes: Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.

Frontline Treatment With Imatinib Mesylate in Chronic Myeloid Leukemia Patients in Early Chronic Phase: a Very Long-Term Analysis by the GIMEMA CML Working Party

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 258-258 ◽  
Author(s):  
Fausto Castagnetti ◽  
Gabriele Gugliotta ◽  
Massimo Breccia ◽  
Giorgina Specchia ◽  
Tamara Intermesoli ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Chronic Phase ◽  
Working Party ◽  
Molecular Response ◽  
Advisory Committees ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival

Abstract Background The chronic myeloid leukemia (CML) therapeutic scenario has been enriched by the approval of second generation TKIs as frontline treatment of early chronic phase (ECP) patients, but imatinib mesylate (IM) still represents the standard for many patients. The long term outcome is extremely important to assess the treatment efficacy and to decide on the allocation of resources. The phase 3 trials comparing second generation TKIs versus standard-dose IM have not still demonstrated a clear improvement in terms of progression-free survival and overall survival. In the IRIS trial, at 8 year, 55% of patients were still on IM and the overall survival (OS) was 85%. Other published reports have shorter follow-up. Aims and Methods To assess the very long-term outcome of CML patients treated frontline with IM, we analyzed 559 patients enrolled within 3 multicentric prospective studies conducted by the GIMEMA CML Working Party (NCT00514488, NCT00510926, observational trial CML023). Definitions: major molecular response (MMR), BCR-ABLIS ratio <0.1%; deep molecular response (MR4.0), detectable disease ≤ 0.01% BCR-ABLIS or undetectable disease with ≥10,000 ABL transcripts; progression, transformation to accelerated or blastic phase; failure, according to 2013 ELN criteria; event, treatment discontinuation for any reason or lost to follow-up. Information on survival and progression were regularly collected. All deaths, at any time and for any reason, were included. All the analysis have been made according to the intention-to-treat principle. Results Baseline demographics characteristics: median age: 52 years (extremes 18-84 years); male sex: 60%; high Sokal, high Euro and high EUTOS scores: 22%, 7% and 7%, respectively; clonal chromosomal abnormalities (CCA) in Ph+ cells: 4% (not evaluable in 32% of patients for insufficient number of metaphases); e13a2 BCR-ABL transcript: 36%. Median follow-up: 76 (7-99) months. The cumulative incidence of complete cytogenetic response (CCyR), MMR and MR4 was 88%, 85% and 61%, respectively. The median time to CCyR, MMR and MR4 was 6, 7 and 42 months, respectively. Patients with high Sokal, high Euro and high EUTOS scores had significantly lower overall estimated probability of CCyR and MMR with respect to low and intermediate risk patients. A high Sokal score also predicted a significantly inferior probability of MR4; patients with high Euro and high EUTOS score had lower overall estimated probability of MR4, but the difference were not statistically significant. The reasons for IM discontinuation were: lack of efficacy (19%), toxicity or death (9%), withdrawal of informed consent (3%); 4% of patients were lost to follow-up. The 8-year event-free survival (EFS), failure-free survival (FFS), progression-free survival (PFS) and OS were 55% (95% CI: 51-60%), 66% (95% CI: 61-70%), 84% (95% CI: 78-89%) and 85% (95% CI: 79-90%), respectively. A high Sokal and a high Euro scores were able to identify patients with significantly lower probability of EFS, FFS, PFS and OS with respect to the other patients. High EUTOS score patients had significantly poorer EFS and FFS, but PFS and OS differences were not significant. Age, performance status and e13a2 transcript resulted independent prognostic factors on PFS and OS. Conclusions Until now, the available data on the very long-term outcome of newly diagnosed chronic phase CML patients treated frontline with imatinib are limited to a company sponsored study (IRIS study). The GIMEMA CML Working Party provided an unbiased overview of the long-term imatinib therapeutic effects in a multicentric nationwide experience. These results should be taken into consideration to make treatment decision concerning the choice of the first line TKI, particularly in low risk patients. Acknowledgments University of Bologna, BolognaAIL, COFIN, Fondazione Carisbo. Disclosures: Castagnetti: Novartis Farma: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Gugliotta:Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Abruzzese:BMS, Novartis: Consultancy. Soverini:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; ARIAD: Consultancy. Cavo:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millennium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

scholarly journals Long-Term Outcome of Chronic Phase Chronic Myeloid Leukemia Patients Treated with Nilotinib Front-Line

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 44-45
Author(s):  
Franck E Nicolini ◽  
Vincent Alcazer ◽  
Pascale Cony-Makhoul ◽  
Stephanie Dulucq ◽  
Sandrine Hayette ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Chronic Phase ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Front Line ◽  
Advisory Committees ◽  
Long Term Outcome

Nilotinib (NIL) 600 mg daily has demonstrated its superiority over Imatinib 400 mg daily in terms of response and incidence of deep molecular response in the front-line chronic phase (CP) CML setting. In this observational study we have retrospectively analyzed the outcome of in- and out-study 202 patients (pts) treated in this setting with NIL 600 mg front-line, in "real-life" conditions. All pts with newly diagnosed adult CP-CML receiving NIL 300 mg BID alone front-line between 10/2007 and 06/2020, were eligible for this study. Data were retrospectively collected according to the current French regulations with pts' information. All pts were assessed and followed according to ELN recommendations 2003, 2006, and 2009 along treatment and to the recommendations from the French group of CML (D. Rea et al., Cancer 2018) in case of TFR. In this regard, a TKI was resumed if loss of MMR. All BCR-ABL1 assessments were performed in the 3 reference laboratories, standardised and expressed in % (IS) with ≥32,000 copies of ABL1 as control. The primary endpoints were the rate of molecular responses in the long-term and the (vascular) safety of Nilotinib. Secondary endpoints were the kinetics of molecular response, survival and safety of Nilotinib. Survival (OS, PFS & EFS) was defined according to ELN (J. Guilhot et al. Blood 2012). Two hundred and two patients were reported with 44% females and 56% males with a median age at diagnosis of 50.4 (17.5-83) years, and 26% of them had cardiovascular risk factors at onset (tobacco abuse 11%, hypercholesterolemia 9.3%, diabetes 1.45%, none with past history of cardiovascular events [CVE]). ELTS scores were high in 14%, intermediate in 31% and low in 55% of pts. Twenty-four (12%) pts harboured additional chromosomal abnormalities at diagnosis. The median follow-up after NIL initiation was 61.5 (1-147.5) months. At last follow-up 113 pts (55%) are not on NIL anymore for toxicities, TFR or resistance reasons. Twenty-eight (14%) pts present an arterial event on NIL (18% PAOD, 14% angina pectoralis, 7% myocardial infarction, 14% stroke, 47% others such as atrial fibrillation, cardiomyopathy...), that occurred after a median of 26 (0.6-98.5) months on NIL. Forty-six (22.5%) pts reached TFR criteria and stopped NIL after a median of 58.5 (27-126) months. The cumulative incidence (CI) rates of MMR at 1, 2 and 5 years were 64 (57-71)%, 79.4 (75.45-83.35)% and 95 (92-98.5)% respectively. For MR4, those were 35.5 (29-42)%, 60 (52-67)% and 82 (74.5-89)% respectively; and for MR4.5, were 14 (9-19)%, 31 (24-28)% and 62 (54-70.5)% respectively. The CI of sustained MR4.5 (i. e. patients eligible for TFR: MR4.5 ≥2 years) was observed in 30 (23-37)% at 3 years, 45.5 (36-55)% at 5 years and 52.5 (41.5-64)% at 6 years (Figure). The CI of patients entering TFR was 16.75 (10.5-23)% at 5 years and 51.94 (37.31-66.57)% at 10 years with a survival without MMR loss of 70.7 (58- 86)% at 1 year and 65.26 (50.6-84)% at 5 years. Nine (4.5%) pts progressed towards accelerated phase (4 pts) or BC (2 lymphoid, 3 myeloid) responsible for 5 deaths at latest follow-up. Among NIL resistant patients screened, 15 were harbouring ABL1 mutations (5 Y253H, 3 E255K, 3 T315I, 1 M244V, 1 G250E, 1 F359V, 1 V299L). Overall, 10 patients died (5 from CML, 5 from unrelated causes). The probability of OS was 95.75 [95%CI: 92.9-98.7]% at 2 years and 94.8 [91.5-98.3]% at 5 years, for PFS it was 94.92 [91.7-98.2]% at 2 years and 89.5 [84.7-94.6]% at 5 years, and EFS it was 78 [72.3-84]% at 2 years and 60.25 [53.3-68.1]% at 5 years. Regarding sustained MR4.5, univariate analysis showed that female gender (HR=2.46 [1.50-4.02], p&lt;0.001) and low ELTS (HR=0.41 [0.22-0.76], p&lt;0.004) had a significant impact, while multivariate analysis confirmed the role of these 2 factors (HR=2.31 [1.41- 3.79], p=0.001 and HR= 0.52 [0.30- 0.90], p=0.02) in addition to high ELTS (HR= 0.28 [0.14- 0.58], p&lt;0.001). Univariate and multivariate analyses demonstrated that only age impacted on the CI of CVE (HR= 1.07 [1.04-1.10], p&lt;0.001, and HR=1.07 [1.04-1.10], p&lt;0.001). NIL first-line efficiently limits progression of newly diagnosed CP-CML patients and provides high rates of sustained MR4.5, allowing TFR in a substantial proportion of pts. However, the onset of arterial occlusive events, especially in the elderly is a matter of concern in the choice of this compound at treatment initiation. Disclosures Nicolini: Incyte: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Sun Pharma Ltd: Consultancy. Cony-Makhoul:BMS: Speakers Bureau; Incyte Biosciences: Speakers Bureau; Pfizer: Consultancy; Novartis: Consultancy; BMS: Consultancy. Dulucq:Incyte: Speakers Bureau; Novartis: Speakers Bureau. Cayuela:Novartis: Speakers Bureau; Incyte: Speakers Bureau. Rea:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mahon:ARIAD: Honoraria; Pfizer: Honoraria; Novartis Pharma: Honoraria, Research Funding; BMS: Honoraria. Etienne:Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau.

scholarly journals Long-Term Outcomes of Chronic Myeloid Leukemia Patients Who Lost Undetectable Molecular Residual Disease (UMRD) after Imatinib Discontinuation: Korean Imatinib Discontinuation Study (KIDS)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1643-1643 ◽  
Author(s):  
Sung-Eun Lee ◽  
Joon Seong Park ◽  
Hyeoung-Joon Kim ◽  
Sung-Hyun Kim ◽  
Dae Young Zang ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Residual Disease ◽  
The Other ◽  
Risk Scores ◽  
Late Relapse ◽  
Molecular Response ◽  
Long Term Follow Up

Background The recent discontinuation clinical trials have demonstrated that IM discontinuation can be employed based on clinical study in patients who had enough IM therapy and undetectable molecular residual disease (UMRD) durations prior to IM discontinuation. Moreover, treatment rechallenge in patients with molecular recurrence lead a second deep molecular response, suggesting that IM discontinuation is safe. However, the issues on the definition of molecular relapse requiring treatment resumption and the occurrence of late relapse with a long-term follow-up after IM discontinuation are important. Therefore, here we analyzed the long-term follow-up results of the patients who lost UMRD after IM discontinuation Methods CP CML patients who were treated with IM for more than 3 years and had undetectable levels of BCR-ABL1 transcripts determined by quantitative reverse transcriptase polymerase chain reaction (PCR) for at least 2 years were eligible for KID study and in cases of MMR loss after 2 consecutive assessments, IM treatment was re-introduced. After IM resumption for MMR loss, the molecular response was evaluated every month until MMR was re-achieved and every 3 months thereafter. The second stop was permitted in the patients who were in second UMRD for at least 2 years. Results Between October 2010 and June 2015, a total of 126 patients (70 females, 56 males) were enrolled on KID Study, with a median age of 47 years (range, 18-82), the percentages of patients with low, intermediate and high Sokal risk scores were 33%, 25% and 15%, respectively with unknown Sokal risk scores in 27%. And the median time on IM therapy and the median duration of sustained UMRD prior to discontinuation were 83 months (range, 32-141) and 41 months (range, 22-131), respectively. After a median follow-up of 62.6 months (range, 4.9-100.8 months) after IM discontinuation, 83 patients (65.9%) lost UMRD. Among them, 56 (67.5%) patients lost MMR in 2 consecutive analyses. The other 27 (32.5%) patients who lost UMRD but not MMR exhibited different patterns of BCR-ABL1 kinetics: 8 patients spontaneously re-achieved UMRD after a median time of 2.8 months (range, 0.9-3.0 months), and 19 patient showed fluctuation of BCR-ABL1 transcript under the level of 0.1% on IS for a median 19 months (range, 3-34), and then spontaneously returned and maintained UMRD for a median 31 months (range, 2-64). Of 73 patients who lost MR4.0, the rate of MMR loss was 76.7%. Out of 56 patients with molecular relapse, 54 patients (except two patients who restart radotinib) were re-treated with IM, all patients (except one patient lost follow-up) re-achieved MMR at a median of 1.9 months (range, 0.0 - 5.4 months) after resuming treatment. Among them, two patients who re-achieving of MMR after resuming IM therapy lost MMR again; One patient who relapsed at 53.2 months after IM discontinuation, despite re-achieving MMR 1.4 later after IM restarting, suddenly progressed to blast crisis at 6 months after restarting IM and in spite of switching to dasatinib and ponatinib, she died. Another patient lost MMR at 7.4 months after IM discontinuation and re-achieved MMR 1.7 later after IM restarting, but progressed to AP on the assessment 32 months later. The patient switched to dasatinib and lost follow-up. Among the patients who maintained a second UMRD for at least 2 years after IM resumption, 23 patients entered into a second IM stop. With a median follow-up of 29.5 months (range, 9-63 months) since second IM stop, 15/23 patients (65%) lost MMR after a median 2.9 months (range, 1.8-30.7 months), which was similar to those of the first IM discontinuation [median 3.7 (range, 1.8-20.8 months)]. The patients who lost MMR were retreated with IM for a median of 24.5 months (range, 1.2-49.7 months); 14 patients re-achieved MMR and one patient was in therapy for 1.2 months. Conclusions Our results showed that 67.5% and 76.7% of patients who lost UMRD and MR4.0, respectively resulted in MMR loss, and the other patients were below MMR without re-treatment, suggesting loss of MMR can be chosen for treatment re-challenge. Overall, IM discontinuation could be applied with approximately 55% of probability of sustained MMR in the long term. In addition, we demonstrated that a second attempt might be possible. Further studies on the predictors to select patients for a trial of second stop are warranted. Disclosures Kim: Il-Yang co.: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; BMS: Research Funding; Novartis: Research Funding.

Helicobacter pylori eradication in gastric MALT lymphoma: Results of 316 patients treated inside and outside of a clinical trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7584-7584
Author(s):  
T. Wündisch ◽  
A. Günther ◽  
C. Mösch ◽  
M. Huynh ◽  
M. Stolte ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Residual Disease ◽  
Remission Rate ◽  
Early Stage ◽  
Prospective Trial ◽  
Gastric Malt Lymphoma ◽  
Term Outcome ◽  
Long Term Outcome

7584 Background: Cure of infection induces remissions in most patients with early stage Helicobacter pylori- (Hp-) positive gastric MALT (mucosa-associated lymphoid tissue) lymphoma (GML). We compared the long-term outcome of 120 patients treated within a multicenter trial to that of 196 routinely treated patients. Methods: 120 patients with stage I1E disease from a prospective trial (cohort 1) were compared to 196 patients with GML treated outside a trail by sole Hp-eradication (cohort 2). The latter were evaluated in retrospect and only a minority had a complete staging at diagnosis. Histology was the standard for remission evaluation in all patients and performed by the same pathologist (MS). B-cell-clonality and the t(11;18) were assessed in cohort 1-patients. Results: Median endoscopic follow-up was 79 months (range, 1–121) in cohort 1-patients and 27 months (range, 0–120) in cohort 2-patients. In 41% of the cohort 2-patients no or one control endoscopy was performed after a first CR. Most patients are in continuous complete histological remission in both cohorts. 3 cohort 1- and 5 cohort 2-patients relapsed. 16 cohort 1- and 13 cohort 2-patients exhibited histological residual disease (RD) during follow up after a first CR; a watch-and-wait strategy was applied, and most entered into a second CR. Conclusions: Hp-eradication results in long term CR in the majority of patients with GML in both cohorts. Duration of remission, rate of relapse, and RD were similar, regardless of incomplete staging and follow-up procedures and higher age in the cohort 2-patients. No significant financial relationships to disclose.

scholarly journals Long-Term Follow-up of the Randomized Controlled Study in Patients with Newly Diagnosed Severe Aplastic Anemia Treated with ATG, Cyclosporine, with or without G-CSF: On Behalf of the SAA Working Party of the EBMT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1307-1307
Author(s):  
André Tichelli ◽  
Regis Peffault De Latour ◽  
Jakob R. Passweg ◽  
Cora Knol ◽  
Gérard Socié ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Late Complications ◽  
Solid Cancer ◽  
Advisory Committees ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Secondary Mds

Abstract Introduction The prospective randomized study on treatment of 192 severe aplastic anemia (SAA) patients with ATG and Cyclosporine (CSA) with and without G-CSF showed that G-CSF added to ATG/CSA decreases the rate of early infection episodes and days of hospitalization in very SAA (vSAA) patients, but has no significant impact on overall survival (OS), event free survival (EFS), relapse, or death rates (Blood, 2011;17:4434). The number of secondary MDS/AML was low, however with a short observation time. Now, 16 years after initiation of the study, a follow-up was planned to evaluate long-term outcome, comparing patients with and without G-CSF. Patients and Methods A total of 192 patients with newly diagnosed SAA, not eligible for stem cell transplantation (SCT) were entered into this prospective randomized multi-center study to receive ATG/CSA with (49.5%) or without G-CSF (50.5%). In 2011, 44 of the 192 patients had died. For the present study the follow-up of the 148 patients alive at time of first publication were requested. There were 49% males (49% G-CSF; 48% no G-CSF), 36% with vSAA (32% G-CSF; 41% no G-CSF). The median age at randomization was 46 years (2-80), 47 (2-80) for the G-CSF and 44 (7-80) for the non-G-CSF group. The median follow-up using reverse KM method was 11.7 years (10.9-12.5). Results Among the 110 survivors (17 missing), 71 (65%) were in CR, 33 (30%) in PR and 6 not in remission (5%), without any difference between the G-CSF and non-G-CSF group (P=0.523). At last follow-up 65 (34%) of the patients have died. Causes of death were infection (26), bleeding (3), SAA unspecified (3), MDS/AML (4), solid cancer (3), transplant related mortality (8), cardiovascular/aging (7), or unspecified (11). There was no difference in the causes of death between patients treated with or without G-CSF. OS at 15 years was 57±12% for the G-CSF and 63±12% for the non-G-CSF group (P=0.927). EFS, including SCT, relapse, non-response at day 120, second MDS/AML, PNH or death as an event, was 24±10% for the G-CSF, and 23±10% for the non-G-CSF group (P=0.367). Nine patients developed florid or morphological signs of MDS/AML, 9 clonal cytogenetic anomaly only, 7 a solid cancer, 18 clinical PNH, 8 avascular osteonecrosis, and 12 chronic kidney disease (No difference between patients treated with or without G-CSF). Cumulative incidence (CI) at 15 years of MDS/AML (isolated cytogenetic anomalies not included) was 5.0±2% (G-CSF) and 7.3±3% (no G-CSF), respectively (P=0.693); for clinical PNH it was 10.1±5% and 13.3±7% (P=0.499), for relapse of responding patients at day 120, 29.8±22% and 25.1±17% (P=0.545), and for chronic kidney failure 16%±12% and 13%±12% (P=0.513), respectively. Forty patients needed a second line immunosuppressive therapy (IST) for relapse (17), refractory disease (8), cyclosporine dependence (6) or isolated cytopenia (9) (G-CSF 26; no G-CSF 16; P=0.291); 16 patients needed a third line IST for relapse (5), refractory disease (7), isolated cytopenia (4) (G-CSF 12; no G-CSF 4; P=0.647). Twenty-eight patients were treated with allogeneic SCT in second or subsequent line (G-CSF 12; no G-CSF 16). CI at 15 years of SCT (competing risk, death without SCT) was 14±8% (G-CSF) and 22%±10% (no G-CSF), respectively (P=0.380). OS at 10 years since SCT was 46±24%. The most important risk factors for patients treated with ATG/CSA with or without G-CSF were age and severity of the disease at randomization: OS at 15 years was 89±12% (<20 years), 81±13% (20-40 years), 55±15% (40-60 years), and 32±16% (>60 years of age), respectively (P>0.001), and 64±5% and 52±7% for patients with SAA and vSAA, respectively (P=0.021). There was no difference between patients treated with or without G-CSF. Finally, the lack of neutrophil response by day 30, which was significant at first evaluation, is still associated with borderline lower survival (46.6±14% versus 67.1±9%; P=0.058). Conclusion: Long-term outcome of SAA patients treated with ATG/CSA was not influenced by supplementing G-CSF in term of OS, EFS, death rates, relapse, PNH, secondary MDS/AML, solid cancer and non-malignant late complications. Due to the pre-cancer nature of the disease and its long-lasting treatment, patients treated with IST are at risk for a number of malignant and non-malignant late complications. It is somewhat disappointing that in this careful followed cohort less than 25% of patients are alive and event-free 10-15 years after initial treatment. Disclosures Peffault De Latour: Pfizer Inc.: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Hoechsmann:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding. Schrezenmeier:Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding. Kulasekararaj:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support . Bader:Neovii: Research Funding; Cellgene: Consultancy; Riemser: Research Funding; Medac: Patents & Royalties, Research Funding; Novartis: Consultancy, Speakers Bureau. Risitano:Pfizer Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amyndas Pharmaceuticals: Consultancy; Alnylam Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Ra Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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