Incidence of hyperlipidemia among patients with chronic myelogenous leukemia (CML) receiving first or second line therapy with dasatinib or nilotinib.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e18108-e18108 ◽  
Author(s):  
Meg Franklin ◽  
Leah Burns ◽  
Samuel Perez ◽  
Deepak Yerragolam ◽  
Dinara Makenbaeva
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Incidence of type II diabetes mellitus among patients with chronic myelogenous leukemia (CML) receiving first or second line therapy with dasatinib or nilotinib.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e18126-e18126 ◽  
Author(s):  
Meg Franklin ◽  
Leah Burns ◽  
Samuel Perez ◽  
Deepak Yerragolam ◽  
Dinara Makenbaeva
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Myelogenous Leukemia ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Myelogenous Leukemia ◽  
Type Ii ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Treatment with Homoharringtonine and Cytarabine in Patients with High Risk Acute Myelogenous Leukemia (AML).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4555-4555
Author(s):  
Naibai Chang ◽  
Jianping Wei ◽  
Shengming Zhao ◽  
Hui Liu ◽  
Yun Fan ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Free Survival ◽  
Leukemic Cell ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Second Line ◽  
Second Line Therapy ◽  
Conventional Dose ◽  
Line Therapy ◽  
Acute Myelogenous

Abstract Objective: To evaluate response of homoharringtonine in patients with high risk AML or as a second-line therapy in patients with AML refractory to anthracycline based chemotherapy. Patients and methods: From Jan 1998-Jan 2006, there were 66 patients enrolled in this regimen. Male:female=40:26. Median age was 47 (17–69). There were 48 newly diagnosed AML, 5 relapsed AML and 13 secondary AML (secondary to MDS) in this group. Among these patients, there were 40 patients untreated previously — 20 patients had unfavourable chromasomal abmormalities, 10 patients had pgp positive, 10 patients had normal chromasome but high CD34 expression on leukemic cells. The remaining 26 patients were previously treated with daunorubincin or mitoxantrane combined with cytarabine at least two cycles and failed to achieve response. Homoharringtonine was given at dose of 4mg/m2/d(2.5mg/m2/d for age≥60 years) intraveniously for 7 days. Cytarabine was given at dose of 100mg/m2/d at same time. The therapy was repeated every 21 days.Post remission therapy was divided into two cohot —same regimen maintainance in 20 cases and cytarabine 1g/m2/d q12h for 4 days at least 4 cycles in 20 cases. Results: 40/66 patients achieved complete remission. 3/66 achieved partial remission. In patients refactory to anthracycline based regimen, the CR rate was 57.7%(15/26). In previously untreated high risk AML patients,the CR rate was 62.5%(25/40). Median disease free survival were 4.25 months (2–30) in cohot 1 and 18 months (12–47) in cohot 2 (P<0.05). CD95(APO-1/Fas) was tested by flow cytometry during treatment. APO-1/Fas (CD95) increased from (9.56±5.58)% to (25.64±0.70)% after induction chemotherapy. Main toxicities were marrow suppression and infection. There were 7 early deaths, 5 patients died of cerebral hemorrage and 2 cardiovascular events. Conclusions: Homoharringtonine is effective in patients with high risk AML. It is also a choice of second line therapy in patients refractory to anthracycline based chemotherapy. Intensive post remission therapy is superior to conventional dose maintainance therapy in high risk AML. One of the ways for homoharringtonine to induce leukemic cell apoptosis is probably through Fas pathway.

Allogeneic Myeloablative Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia in the Imatinib Era.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 970-970
Author(s):  
Jiri Pavlu ◽  
Matthias Klammer ◽  
Ian Gabriel ◽  
Richard Szydlo ◽  
Eduardo Olavarria ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Scoring System ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Prognostic Scores ◽  
Second Line ◽  
Second Line Therapy ◽  
Hematopoietic Stem ◽  
Line Therapy

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is no longer the first treatment option for patients with chronic myelogenous leukemia (CML) but there is a considerable debate about its use as a second line therapy. When used in this indication the second-generation tyrosine kinase inhibitors (2G-TKI) induce complete cytogenetic responses (CCyR) in 40–50% of patients in chronic phase but those without CCyR are unlikely to benefit in long term. It is therefore important to identify groups of patients with a good outcome after transplantation so that this may be offered as second line therapy where appropriate. The outcome of allo-SCT has improved over time so we restricted our analysis to the most recent 8 years to coincide with the introduction of imatinib into clinical practice. 131 patients received myeloablative transplants from January 2000 till December 2007. 67 patients were transplanted in chronic phase (14 in second and 2 in third chronic phase), 46 in accelerated phase and 2 in blastic phase. Forty-nine patients received imatinib at some point prior to transplantation and 30 of these experienced failure of imatinib therapy (as defined by European LeukemiaNet criteria). Conditioning consisted of cyclophosphamide and total body irradiation for 51 recipients of sibling stem cells. In addition in vivo T cell depletion with anti CD52 antibody (Campath 1H) was used for 80 unrelated donor transplants. The median age of the patients was 33.4 (15 to 56) years and the median disease duration at transplant was 13 (2 to 105) months. The probability of overall survival (OS) at 3 and 5 years was 64.8% and 62.6% respectively. We confirmed the prognostic value of the EBMT risk assessment score (Gratwohl) and pretransplant level of the C-reactive protein (CRP) and developed a combined additive pretransplant scoring system based on these predictive factors (EBMT risk assessment score plus 0 for CRP <2 mg/L, 1 for CRP from 2 to 10 mg/L, and 2 for CRP >10 mg/L). This identified 5 prognostic groups (Figure 1) with 3yr probabilities of survival of 92.6% (N= 27, score 0–1), 86.2% (N=29, score 2), 58.2% (N=29, score 3), 47.5% (N=20, score 4) and 30.8% (N=26, score 5 or more). The patients who failed imatinib (N=30) had significantly higher prognostic scores on the above described pre-transplant scoring system compared to the rest of patients transplanted (p=0.001). However, in a multivariate analysis adjusted for prognostic scores, their OS was significantly better (p=0.032). The OS in the best prognostic group is comparable with that of unselected patients treated with imatinib and it is possible that their long-term survival might be better. Allogeneic transplantation is unlikely to be preferred as the first line therapy even in selected patients due to its higher early mortality but our data support its use as second line therapy in patients in chronic phase who failed imatinib and have poor pre-2G-TKI predictive factors for CCyR as determined previously at our institution (namely Sokal risk score at diagnosis, the best cytogenetic response obtained on imatinib, G-CSF requirement during imatinib therapy and time from detection of imatinib failure to onset of 2G-TKI therapy) but achieved good score on the pre-transplant scoring system. It should also be used for those whose disease is more advanced where the 2G-TKI do not offer durable remissions. Figure 1 Figure 1.

Clinical Outcomes In Patients with Chronic Myelogenous Leukemia (CML) and the BCR-ABL 35 Base Pair (bp) Intron 8 Insertion Mutation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3408-3408 ◽  
Author(s):  
Ellin Berman ◽  
Jorge Cortes ◽  
Hagop M. Kantarjian ◽  
Thomas O'Hare ◽  
Christopher Eide ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Research Funding ◽  
Kinase Domain ◽  
Myelogenous Leukemia ◽  
Insertion Mutation ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Abl Kinase ◽  
Line Therapy

Abstract Abstract 3408 More than 80% of patients (pts) with CML who are treated with imatinib as first line therapy achieve a complete cytogenetic response (CCR), although approximately 20% of these pts may ultimately progress. The most common mechanism for loss of response is acquired resistance to imatinib due to the development of a point mutation in the ABL kinase domain of BCR-ABL that interferes with optimal imatinib binding. An alternatively spliced BCR-ABL mRNA with a 35 bp insertion between exons 8 and 9 was first described in 2008 (Laudadio, 2008: Lee, 2008); this results in a BCR-ABL protein with 10 novel amino acids inserted after amino acid 474 within the C- terminus of the kinase domain followed by a stop codon. However, clinical responses to imatinib, dasatinib, or nilotinib have not been previously described in patients with this mutation. We retrospectively identified 40 pts who had this mutation detected and describe their clinical outcomes. Of the 40 patients, 24 were male, and the median age was 50, (range 16–70). Six patients had received treatment prior to 2001, and all 40 patients began initial therapy with imatinib. Twenty nine pts had mutation testing done because of either disease progression or lack of response to imatinib and in 9 pts, the mutation was detected during retrospective analysis. Two pts had the mutation detected at the time of diagnosis (one is still on imatinib). Six pts had additional mutations detected simultaneously: E255V, E355G, E450G, T315I with F416L, T315I with E255K, and one with another insertion between exons 4 and 5. The median time from start of imatinib to insertion mutation detection was 36 months (range 0–189). Thirty of the 40 pts (75%) either did not tolerate (n=2) or progressed while on therapy with imatinib (n=28). Eleven pts remain on imatinib, although 5 are on doses of 600 mg/day or higher. Eighteen of the 30 pts (60%) who failed imatinib were changed to dasatinib as second line therapy; 10 of these (56%) did not respond and were changed to nilotinib as third line therapy. Ten of the 30 pts (30%) who did not respond to imatinib were changed to nilotinib as second line therapy; 3 pts achieved an MCR. In summary, this report provides the first clinical summary of pts with CML who have the 35 bp intron 8 insertion mutation. Although it is not clear whether this insertion mutation directly leads to imatinib resistance, given that 75% of pts progressed on standard dose imatinib, other alternative therapies should be considered once this mutation is detected. However, given the small numbers of pts treated with dasatinib or nilotinib as second line therapy, it is difficult to determine whether either has a superior effect. Results of biochemical and cellular studies comparing the relative sensitivity of the BCR-ABL 35 bp intron 8 insertion mutation to several ABL kinase inhibitors will be presented. Table 1. Response summary for patients with BCR-ABL 35 bp intron 8 insertion mutation. Number of patients (%) Failure or progression on first-line imatinib 30/40 (75%) Failure or progression on second-line dasatinib 10/18 (56%) Failure or progression on second-line nilotinib 7/10 (70%) Kinase domain mutation concurrently detected with 35 bp insertion mutation 6/40 (15%) Received non-TKI treatment prior to front-line imatinib 6/40 (15%) Disclosures: Berman: Novartis Inc: Research Funding. Kantarjian:Genzyme: Research Funding; Eisai: Research Funding. Druker:Molecular MD: Equity Ownership.

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