scholarly journals Response to High Dose Imatinib and Long-Term Outcome in Children and Adolescents with Previously Untreated Chronic Myeloid Leukemia in Chronic Phase. the Italian Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1812-1812
Author(s):  
Fiorina Giona ◽  
Maria Caterina Putti ◽  
Giuseppe Menna ◽  
Concetta Micalizzi ◽  
Nicola Santoro ◽  
...  
Keyword(s):  
Side Effects ◽  
Median Time ◽  
Chronic Phase ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Term Outcome ◽  
Long Term Outcome

Abstract Imatinib (IM) is an established first-line treatment for children with chronic myeloid leukemia (CML). However, the most effective dosage of IM and overall management of newly-diagnosed childhood CML in chronic phase (CP) are not well defined. This study was designed to evaluate (a) the response to IM at a dosage equivalent in terms of drug exposure to the 600 mg daily utilized in adults and (b) the long-term outcome in newly-diagnosed children and adolescents with CML. Patients aged <18 years with a diagnosis of CML in CP were treated with IM at a dosage of 340 mg/m2/day. Cytogenetic analyses were planned on bone marrow (BM) cells before and during IM therapy as well as quantitative RT-PCR on peripheral blood (PB) monthly and on BM every 3 months. Partial cytogenetic response (PCyR) was considered as the presence of Ph+ cells between 0 and 35%. Molecular response (MR) was considered as <0.01% BCR-ABL1 IS, while major MR (MMR) was defined as <0.1% BCR-ABL1 IS. This study was approved by the Istitutional Review Boards of each participating Institution. Between December 2002 and February 2014, 41 CML patients in CP (females: 13, males: 28; age <10 years: 13 patients) were recorded from 9 Italian pediatric centers. Twenty-seven patients (66%) have a follow-up >24 months. IM was started in all patients, including 16 with an HLA-matched sibling. The dosage of IM was modulated according to the occurrence of >2 WHO side-effects or response, mainly during the first 6 months of treatment. Forty patients are evaluable for treatment results. Median administered dosage of IM was 309 mg/m2/day, higher in males than in females (326 mg/m2vs 245 mg/m2, p .015) and in those younger than 10 years (314 mg/m2vs 262 mg/m2). Twenty-four patients (60%) experienced isolated or combined side effects: hematologic toxicity (medullary hypoplasia [n=1], neutropenia [n=7] and/or thrombocytopenia [n=6], anemia [n=1]) and/or extra-hematologic toxicity (arthralgia/myalgia [n=8], nausea [n=1], vomiting [n=1], diarrhea [n=1], abdominal pain [n=2], hepatitis [n=1], skin rash [n=2]. Persistent >3 WHO adverse events led to IM discontinuation in 6 patients (15%). At 3 months of IM treatment, hematologic response and PCyR rates were 91% and 54%, respectively; BCR-ABL1 transcript levels <10% were found in 69% and 75% of patients on BM and on PB cells, respectively. At 6 months, 77% of patients was in CCyR; 56% and 66% of patients showed BCR-ABL1 transcript levels <1% on BM and on PB cells, respectively. At 12 months, MMR was detected in 66.4% and 71.4% of patients on BM and on PB cells, respectively; BCR-ABL1 IS <0.0032% was found in 21% and 14% of patients on BM and on PB cells, respectively. All but 1 patient achieved a response. Overall, 94% obtained a CCyR at a median time of 6.4 months. Fourteen of 25 (56%) and 13/17 (76%) evaluable patients obtained a MR on BM and on PB cells at a median time of 13 and 15 months, respectively. Intermittent therapy (IM at the same daily dosage for 3 weeks a month) was started in 6 patients with a sustained MR; thereafter, 2 adolescents with <0.0032% BCR-ABL IS lasting >7years successfully discontinued IM and 2 patients resumed continuous IM because of an increased BCR-ABL transcript. IM was interrupted in 8/33 (24%) responder patients, 4 of them in BCR-ABL1 IS<0.1%, after a median time of 7 months because they underwent an allogeneic stem cell transplant (SCT). Treatment was also discontinued in 6 patients in continuous IM because of a disease recurrence (median response duration: 37 months; range, 21-115). Overall, 12 patients (30%) underwent a SCT after a median of 7.7 months: 8 from an identical sibling (BCR-ABL1 IS <0.1% in 3), 3 from a MUD and 1 from an umbilical cord blood. Three patients, transplanted from an identical sibling, had disease recurrence after 24, 36 and 83 months, respectively. Estimated probabilities of failure-free survival was 50% at 8 years for patients submitted to an SCT and 60% at 10 years for those still receiving IM. At the last follow-up, all patients are alive at a median of 44.6 months. In our experience, IM at a daily dose of 340 mg/m2 is effective in newly-diagnosed CML children with responses rates higher than those reported in children treated with IM at lower dosage. Considering the long-term follow-up, high-dose IM allowed to safely discontinue treatment in some patients with a deep MR; furthermore, it did not worsen the outcome both in patients submitted to a SCT and in those with disease progression or side-effects. Disclosures Saglio: BMS: Consultancy, Fees for occasional speeches Other; Novartis: Consultancy, Fees for occasional speeches, Fees for occasional speeches Other; Pfizer: Consultancy, Fees for occasional speeches, Fees for occasional speeches Other; ARIAD: Consultancy, Fees for occasional speeches, Fees for occasional speeches Other.

Long-Term Outcome for Patients With Nonmetastatic Osteosarcoma of the Extremity Treated at the Istituto Ortopedico Rizzoli According to the Istituto Ortopedico Rizzoli/Osteosarcoma-2 Protocol: An Updated Report

2000 ◽  
Vol 18 (24) ◽  
pp. 4016-4027 ◽  
Author(s):  
Gaetano Bacci ◽  
Stefano Ferrari ◽  
Franco Bertoni ◽  
Pietro Ruggieri ◽  
Piero Picci ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Tumor Necrosis ◽  
Poor Responders ◽  
High Dose ◽  
Second Malignancies ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Long Term Follow Up

PURPOSE: To provide an estimate of long-term prognosis for patients with osteosarcoma of the extremity treated in a single institution with neoadjuvant chemotherapy and observed for at least 10 years. PATIENTS AND METHODS: Patients with nonmetastatic osteosarcoma of the extremity were preoperatively treated with high-dose methotrexate, cisplatin, and doxorubicin (ADM). Postoperatively, good responders (90% or more tumor necrosis) received the same three drugs used before surgery, whereas poor responders (less than 90% tumor necrosis) received ifosfamide and etoposide in addition to those three drugs. RESULTS: For the 164 patients who entered the study between September 1986 and December 1989, surgery was a limb salvage in 136 cases (82%) and a good histologic response was observed in 117 patients (71%). At a follow-up ranging from 10 to 13 years (median, 11.5 years), 101 patients (61%) remained continuously free of disease, 61 relapsed, and two died of ADM-induced cardiotoxicity. There were no differences in prognosis between good and poor responding patients. ADM-induced cardiotoxicity (six patients), male infertility (10 of the 12 assessable patients), and second malignancies (seven patients) were the major complications of chemotherapy. Despite the large number of limb salvages performed, only four local recurrences (2.4%) were registered. CONCLUSION: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with nonmetastatic osteosarcoma of the extremity and amputation may be avoided in more than 80% of them. Because local or systemic relapses, myocardiopathies, and second malignancies are possible even 5 years or more after the beginning of treatment, a long-term follow-up is recommended for these patients.

High-dose imatinib mesylate treatment in patients (Pts) with untreated early chronic phase (CP) chronic myeloid leukemia (CML): 2.5-year follow-up

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6535-6535 ◽  
Author(s):  
E. Aoki ◽  
H. Kantarjian ◽  
S. O’Brien ◽  
M. Talpaz ◽  
F. Giles ◽  
...  
Keyword(s):  
Standard Dose ◽  
Chronic Phase ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Molecular Response ◽  
Molecular Responses ◽  
Pre Treatment ◽  
Grade 3

6535 Background: The standard dose (SD) of imatinib for CP CML is currently 400 mg daily, but higher doses (HD) may be more effective. We conducted 2 consecutive trials using HD imatinib (i.e., 400mg twice daily) in previously untreated early CP CML pts. This is an updated analysis of the longer follow-up. Methods: A total of 175 previously untreated pts received HD imatinib. We compared the results with a previous study using SD imatinib (400mg/day) in untreated pts with early CP CML (N=50). Results: Cytogenetic and molecular responses were evaluable in 222 pts (N=49 at SD, 173 at HD) and 217 pts (N=46 at SD, 171 at HD), respectively. In HD group, Sokal risk classification was good in 69%, intermediate in 29%, and poor in 11% of pts. There were no differences in pre-treatment characteristics between two groups. The median age was 48 years in both groups. Median follow-up is 53 months for SD and 30 months for HD group. Patients treated with HD had a higher rate of complete cytogenetic responses (90% vs 78% with SD, p=0.03) and these occurred earlier, with 69% achieving this response after 6 months of therapy vs 45% with SD (p=0.001). The cumulative incidence of major molecular response was significantly better in HD group (p=0.03), and this response was also observed earlier in HD group: at 12 months 54% in HD and 24% in SD group had achieved this response (p=0.001). At 24 months, 19/70 (27%) evaluable pts with HD versus 3/31 (10%) of pts in SD group achieved complete molecular remission. Four pts (2%) in HD group and 4 pts (8%) in SD group have progressed to advanced phases (p=0.05). There was a trend in favor of the HD group for transformation-free-survival but it was not statistically significant (p=0.07). Overall survival is excellent in both groups (24 month survival, 99% with HD vs 98% with SD; p=0.24). Grade 3 or 4 hematologic toxicity was more frequent in HD group whereas extramedullary toxicity was similar in two groups. The median actual dose in HD group was 800 mg at 12 months, with 39% patients requiring dose reduction at some point. Conclusions: High-dose imatinib provides higher rates of complete cytogenetic responses and earlier molecular responses with some increase myelosupression. The long-term benefit of earlier responses remains to be demonstrated. [Table: see text]

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

scholarly journals Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8096-8096 ◽  
Author(s):  
Geetika Srivastava ◽  
Vishal Rana ◽  
Martha Lacy ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Entire Cohort ◽  
Dexamethasone Therapy

8096 Background: The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma. While the short-term outcomes with respect to response and toxicity is well-known, long-term outcome with this combination as initial therapy is not well described. Methods: We studied 286 consecutive patients with newly diagnosed MM seen at our institution, who received initial therapy with Len-Dex, and who had complete follow up records. Data regarding the clinical course was obtained from medical records. Results: The median (range) age at diagnosis was 63 (28-92) yrs; 166 (58% were ≤ 65 yrs and175 (61%) were male. The median estimated follow-up was 3.9 yrs (95% CI, 3.4, 4.2) and 203 (71%) pts were alive at the time of last follow up. The median estimated duration on Len-Dex was 5.3 mos (95% CI, 4.6, 6.4). The best overall response (≥PR) was 72%, including 26% with VGPR or better and 14 (5%) not being evaluable for a response. At last follow up, 41 (14%) patients were continuing on therapy. There were 93 pts (32%) who stayed on therapy for 12 months or more. Among these patients, the ORR was 86%, including 45% with VGPR or better. The median overall survival (OS) for the entire cohort from diagnosis was 7.4 yrs (95% CI; 5.8, NR) and the estimated 5-yr survival was 67%. There were 16 (5.5%) pts who died within a year of diagnosis. The median time to first disease progression, irrespective of transplant status, was 30.2 mos (95% CI, 25, 42). Overall, 143 (50%) of the patients have gone to stem cell transplant. Censoring those patients who proceeded to SCT prior to relapse at the time of BMT, the median TTP was 25.5 mos (95% CI, 22, 29). The median OS was 7.4 yrs for those ≤65 yrs, compared with 6.2 yrs for the older patients (P=0.01). The 5-yr OS estimate for patients in ISS stage 1, 2 and 3 were 82, 65, and 44 months respectively. Conclusions: The current study provides long-term estimates of responses and survival in a series of patients treated initially with lenalidomide and dexamethasone. The median survival of nearly 8 years reflects the efficacy of the novel agents both at diagnosis and at relapse and confirms the survival improvements seen in MM in the last decade.

xxx

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8123-8123
Author(s):  
C. Tarella ◽  
M. Zanni ◽  
A. Rambaldi ◽  
F. Benedetti ◽  
R. Passera ◽  
...  
Keyword(s):  
Complete Remission ◽  
High Dose ◽  
Low Grade ◽  
High Grade ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Long Term Survival

8123 Background: The high-dose sequential (HDS) chemotherapy approach, including early dose-intensification and autograft with peripheral blood progenitor cells (PBPC), was introduced several years ago (Gianni & Bonadonna, 1989); subsequently, it has been broadly used in the management of both non-Hodgkin s (NHL) and Hodgkin s Lymphoma (HL). The outcome of a large series of lymphoma patients treated with the HDS approach at 10 GITIL Centers is reported. Methods: Data have been collected on 1,266 patients, who received either the original or slightly modified HDS regimens. There were 213 HL and 1,053 NHL (630 intermediate/high-grade, 423 low-grade); median age was 46 yrs. Overall, 671 (53%) patients had refractory/relapsed disease, 595 (47%) were at diagnosis. Most patients were autografted with PBPC; 158 (12%) patients did not undergo autografting due to toxicity, disease progression or poor harvests. Results: Overall, 1,013 (80%) patients reached Complete Remission (CR) following HDS. As to December 2006, 93 (7%) patients died for early/late toxicities, 328 (26%) died for lymphoma, 844 are known to be alive. At a lead follow-up of 18 years, and a median follow-up of 5 yrs, the 5-yr Overall Survival (OS) projection is 64% (S.E.: 2%). The long-term survival was quite favorable in patients achieving a Complete Remission (CR), with a 5-yr OS projection of 76%. The prolonged OS in patients achieving CR was consistent in all lymphoma subtypes, i.e. both low and high-grade NHL (5-yr OS: 77% in both), and HL (5-yr OS: 72%). Patients at diagnosis had a significantly better outcome compared to patients treated for relapsed/refractory disease, again CR achievement was associated with prolonged survival in both subgroups (82% and 69%, respectively, at 5 yrs.). On multivariate Cox survival analysis, CR achievement was the most powerful predictor of long-term survival (HR 0.13, c.i.: 0.10–0.17). Lastly, achieving substantial tumor reduction before autografting had a major influence on the clinical outcome. Conclusions: 1. the HDS program is feasible in a multicenter setting; 2. the long-term outcome is well influenced by the CR status after HDS; 3. the influence of CR achievement on the long-term survival holds true in all lymphoma subtypes, including indolent lymphomas; 4. an adequate pre-autograft tumor debulking may contribute to a favorable long-term outcome. [Table: see text]

Beneficial Effects of Cytogenetic and Molecular Response on Long-Term Outcome in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib (IM): Update from the IRIS Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 166-166 ◽  
Author(s):  
Bengt Simonsson ◽  
Keyword(s):  
Blast Crisis ◽  
Chronic Phase ◽  
Risk Groups ◽  
Low Risk ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Long Term Outcome ◽  
Increased Risk

Abstract Background: IM was proven to be superior to IFN+Ara-C for newly diagnosed pts with CML-CP (O’Brien et al, NEJM 2003). At 42-months of follow-up, 75% of the 553 pts randomized to IM remain on treatment. Of the 553 pts randomized to IFN+Ara-C only 4% are still on IFN+Ara-C. This update analysis is focused on IM pts. Methods: Evaluation included complete hematologic response (CHR), major/complete cytogenetic response (MCyR/CCyR) - defined as 0-35% Ph+ and 0% Ph+ metaphases respectively, major molecular response (MMR) - defined as ≥3 log reduction of bcr-abl transcripts from the standardized baseline, time to progression - defined as loss of CHR/MCyR or evolution to accelerated phase/blast crisis (AP/BC) or death due to any cause, time to AP/BC - defined as evolution to AP/BC or death due to CML, and overall survival. Results: With an average duration of 38 months of IM treatment, the best observed rates of CHR, MCyR and CCyR are 96%, 88% and 81%, respectively. Although the majority of MCyRs were achieved within the first 3 to 9 months, some pts achieved a MCyR and some even a CCyR after more than one year of treatment (Figure 1). The estimated MMR rate at 12 months is 40%. Figure 1 - Observed CHR, MCyR and CCyR during treatment with IM Figure 1 -. Observed CHR, MCyR and CCyR during treatment with IM The estimated progression-free rate at 42 months is 84%; additionally 94% are estimated free of progression to AP/BC (97% of the pts with CCyR and 73% of the pts without CCyR during study, p<0.001). The risk of relapse remains low with no apparent increased risk over time. The yearly hazard for progression to AP/BC is about 2% in each of the 4 years. The overall estimated survival at 42 months is 91% (considering all deaths). The estimated survival was lowest in pts with high risk Sokal score (84%) as compared to 91% in the intermediate risk pts and 94% in the low risk pts (p<0.001). Similarly, the best observed CCyR in the high, intermediate, and low risk groups were 69%, 80% and 88% respectively (p=0.002). In the subset of pts with CCyR the estimated survival at 42 months was 92%, 93% and 97% in the high to low risk groups (p=0.30), indicating that once pts achieve a CCyR, their survival is not significantly different between the Sokal risk groups. Of the 509 pts who were still on treatment at 12 months and had achieved a MCyR by then (n=436), the rate without progression to AP/BC at 42 months was 97% whereas it was only 83% for the 73 pts who did not achieve a MCyR at 12 months (p<0.001). The estimated survival rates at 42 months were 95% and 83% in these two response groups, respectively (p<0.001). Furthermore, for pts who had achieved a MMR at 12 months, the probability of remaining free from progression to AP/BC was 100% at 42 months compared to 95% for pts in CCyR but not in MMR, and 91% for pts not in CCyR at 12 months (p=0.0013). Conclusions: The follow-up confirms the beneficial effect of cytogenetic and molecular responses on long-term outcomes with IM. These results will be further updated using data cut-off of 31-July 2005 to reflect additional 12-months of data (i.e., 54-month follow-up).

Significance of Suboptimal Response to Imatinib, as Defined by the European LeukemiaNet, in Long-Term Outcome for Patients (Pts) with Chronic Phase (CP) Chronic Myeloid Leukemia (CML).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1932-1932 ◽  
Author(s):  
Yesid Alvarado ◽  
Hagop Kantarjian ◽  
Stefan Faderl ◽  
Jan Burger ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Cytogenetic Response ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Complete Hematologic Response ◽  
Starting Dose ◽  
Prognostic Implications ◽  
Definition Of

Abstract The European LeukemiaNet recently published recommendations for evaluating response to imatinib among pts with CML. Criteria for failure and suboptimal responses were proposed. The significance of failure is accepted and constitutes grounds for change in treatment. The prognostic implications of having a suboptimal response are less clear making treatment decisions less clear in this setting. We analyzed the outcome of 281 pts treated with imatinib as frontline therapy for CML in CP: 73 at initial dose of 400mg daily and 208 at 800mg daily. Their median age was 48 yrs (range, 15 to 84 yrs) and their median follow-up 48 months (mo) (2–79 mo). After 3 mo of therapy none of the 273 evaluable pts met definition of suboptimal response according to the European LeukemiaNet, while 3 of 273 (1%) met definition for failure. At 6 mo 10/259 (4%) evaluable had suboptimal response and 9 (3%) failure. At 12 mo 19/246 (8%) had suboptimal and 14 (6%) failure, and at 18 mo 91/224 (41%) had suboptimal and 21 (9%) had failure. The probability of having a suboptimal response at 6 and 12 mo was significantly higher for pts treated with a starting dose of 400mg than those treated at 800mg: at 6 mo [12% suboptimal at 400mg vs 1% at 800mg (p=0.002)] and at 12 mo [17% and 4%, respectively (p&lt;0.001)]. The outcome at 24 months* by the response at specific times was as follows: Time Response % CCyR % MMR % Transf % Event CCyR=Complete cytogenetic remission, MMR=Major molecular remission, Transf=Transformation to accelerated or blast phase, Event=loss of complete hematologic response, loss of major cytogenetic response, transformation, or death 6 mo Optimal 91 60 2 6 Suboptimal 0 0 30 50 Failure 0 0 22 67 P .001 .001 .001 .001 12 mo Optimal 94 63 2 4 Suboptimal 56 25 0 16 Failure 0 0 21 57 P .001 .001 .001 .001 18 mo Optimal 98 85 0 1 Suboptimal 93 39 2 5 Failure 15 0 19 43 P .001 .001 .001 .001

scholarly journals Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study

Blood ◽  
2014 ◽  
Vol 123 (15) ◽  
pp. 2317-2324 ◽  
Author(s):  
Neil P. Shah ◽  
François Guilhot ◽  
Jorge E. Cortes ◽  
Charles A. Schiffer ◽  
Philipp le Coutre ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Imatinib Resistant ◽  
Key Points

Key Points Imatinib-resistant/-intolerant patients with chronic myeloid leukemia in chronic phase can experience long-term benefit with dasatinib. Early (3- and 6-month) molecular and cytogenetic responses were associated with improved progression-free survival and overall survival.

scholarly journals Long-Term Outcome of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Mycosis Fungoides and Sézary Syndrome: The Milan Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4655-4655
Author(s):  
Francesco Onida ◽  
Giorgia Saporiti ◽  
Silvia Alberti Violetti ◽  
Elena Tagliaferri ◽  
Federica Grifoni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Median Time ◽  
Term Outcome ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Reduced Intensity

Abstract Introduction: Although a few novel drugs have recently shown promising activity in mycosis fungoides (MF) and Sézary syndrome (SS), prognosis of patients with advanced stages or refractory disease remain poor, with median survival ranging from 1.4 to 3.4 years (Agar NS et al. JCO 2010). In selected patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential curative strategy. By decreasing transplant-related mortality, reduced intensity (RIC) and nonmyeloablative conditioning (NMA) regimens lead to better outcomes in comparison to myeloablative ones. Here we report long-term outcome of our RIC allo-HSCT experimental program, initiated in 2001. Patients & Methods: As of July 2018, in our Center 40 patients underwent RIC allo-HSCT from HLA-identical sibling (n=16), unrelated donors (UD, n=22 - fully-matched in 10, 1 or 2-mismatch in 12) or haploidentical related donors (n=2). Median age was 52 years (range 19-66). All patients (24 M and 16 F) had stage IIB/IV refractory MF (n=27) or SS (n=13). Median number of previous treatment lines was 6 (range 2-12) while median time from diagnosis to transplantation was 46 months (range 11-264). The source of stem cells has been peripheral blood in 35 patients (87.5%), bone marrow in 4 (10%) and cord blood in 1 (2.5%). Conditioning regimens included FC/TBI200, pentostatin+TBI200, and fludarabine/melphalan in transplants from HLA-identical sibling donor or UD, whereas the TT/Flu/CTX/TBI200 regimen was used in the haploidentical setting. GvHD prophylaxis included CsA/MMF in all patients, with the addition of ATG in cases with UD and post-transplant CTX (50 mg/kg giorni +3 e +4) in haploidentical setting. Results: Full donor chimerism was obtained in 32 out of 37 evaluable patients, in a median time of 2 months (range 1-12). Acute GvHD occurred in 18 patients out of the 32 evaluable (56%), being of grade III-IV in 9 (28%). Chronic GvHD was observed in 10 patients (31%), being extensive in 4 (12%). Of note, the latter were all patients transplanted from HLA-identical sibling (i.e. without ATG). Following transplantation, a complete remission (CR) was achieved in 26 out of the 37 evaluable patients (70%), of whom 4 experienced relapse at +2 (2 pts), +25 and +35 months, respectively. At the last follow-up, 19 patients were alive and 17 (89%) maintained CR after a median follow-up of 80 months (range 4-210). Out of the 11 patients who did not achieve CR, 9 died from progressive disease (median follow-up of 12 months, range 3-31), 1 from a secondary malignancy, while 1 is still alive with disease 62 months after transplant. Transplant-related death occurred in 7 patients (17%), of whom 5 were in CR. In the whole population, the 5-year OS was 52% (95% CI 34-70) [Fig.1] and the 5-year DFS was 43% (95% CI 27-62). However, when MF and SS were analysed separately, 5-yrs DFS were 30% (95% CI 12-51) and 72% (95% CI 38-99), respectively (Fig.2). Apart from diagnosis, outcome appeared to be primarily associated with chemosensitivity and status of disease at transplantation. Conclusions: After a median follow-up longer than 6.5 years, we confirm the efficacy of RIC allo-HSCT as a powerful therapeutic strategy in inducing and maintaining remission in selected patients with chemosensitive advanced-stage CTCL, with results particularly encouraging in SS. Disclosures Cortelezzi: roche: Consultancy; abbvie: Consultancy; novartis: Consultancy; janssen: Consultancy.

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