Outcome of First Salvage Therapy in Core Binding Factor Associated Acute Myelogenous Leukemia Is Less Than Optimal

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2952-2952
Author(s):  
Carmen Fava ◽  
Deborah Blamble ◽  
Susan O’Brien ◽  
Guillermo Garcia-Manero ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Stem Cell ◽  
Salvage Therapy ◽  
Acute Myelogenous Leukemia ◽  
Stem Cell Transplant ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Acute Myelogenous

Abstract Background: Core binding factor (CBF) associated acute myelogenous leukemia (AML) is considered to have a better prognosis compared to that of other patients with AML. Reinduction with cytarabine based therapy followed by allogeneic stem cell transplant is a standard salvage approach. Method: We performed a retrospective analysis of outcome in patients with CBF AML. Results: Between the years 1992 and 2005, 107 patients with CBF AML were treated at M.D. Anderson Cancer Center. Sixty-six (62%) patients had inv 16 abnormality and 41 (38%) had t(8;21) abnormality. Induction chemotherapy regimens included fludarabine and cytarabine with or without granulocyte colony stimulating factor (G-CSF) (66 patients) or idarubicin and cytarabine with/without G-CSF (41 patients). One hundred and one (94%) patients achieved complete remission (CR). After a median CR duration of 159 weeks, 37 (37%) patients relapsed. Relapse rate was 26/66 (39%) among patients with inv 16 abnormality and 11/41 (27%) among those with t (8;21) abnormality. Higher WBC count predicted for relapse (p=.001) and relapse rate did not differ among induction regimens (p=0.1). Salvage chemotherapy included cytarabine based regimen in 22 (59%) patients, clofarabine and idarubicin (2 patients), topoisomerase inhibitor (5 patients), histone deacetylase inhibitor (2 patients) and miscellaneous regimens (6 patients). Sixteen (43%) of the patients with relapsed CBF AML achieved CR after first salvage therapy. Eleven of 26 (42%) patients with inv 16 and 7/11 (64%) of patients with t (8;21) were resistant to first salvage therapy. Thirteen patients (10 in CR) underwent allogeneic stem cell transplant and 12 of them remained in CR post-transplant. Overall survival was significantly worse among patients who relapsed compared to the ones who did not (p=.001). Conclusion: A significant proportion of patients with CBF AML relapse and second remissions can be achieved in less than half the patients. This highlights the need for better induction/consolidation regimens in this group of patients with ‘good-risk’ AML.

Late Relapses in Acute Myelogenous Leukemia: Analysis of Characteristics and Outcome.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 951-951
Author(s):  
Dushyant Verma ◽  
Stefan Faderl ◽  
Susan O’Brien ◽  
Sherry Pierce ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Survival ◽  
Median Duration ◽  
Acute Myelogenous Leukemia ◽  
Stem Cell Transplant ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Acute Myelogenous ◽  
Wbc Count

Abstract The majority of patients with acute myelogenous leukemia (AML) who achieve complete remission (CR) with initial chemotherapy will eventually relapse. Most relapses occur in the first three years and rare patients relapse after being in CR for more than 5 years. We have reviewed retrospectively 2347 patients with AML treated at M D Anderson Cancer Center from January 1980 to July 2008. Of the total cohort, 1366 patients achieved CR and among these 942 patients relapsed. We identified 11 patients (1.16%) who relapsed after being in CR >5 years; these patients are the focus of this analysis. There were 4 females and 7 males. Their median age was 66 years (range 37–79), and their median presentation white blood cell (WBC) count was 2.3 x109/L (range, 1.1–92.3). The FAB classification was M2 in 5 patients, M1, M4, M5, M6 in 1 patient each, and unknown in 2 patients. Initial cytogenetics were diploid in 6, del(7q) in one, miscellaneous in 1, and unavailable in 3 patients. Initial therapy was with combination of idarubicin (Ida) and cytarabine (Ara-C) in 4 patients (1 with additional fludarabine), amsacrine based in 3, daunorubicin (Dauno) single agent in 2 and other agents in 2 patients. All patients except one achieved CR after the first induction course; one patient needed 2 cycles of induction to achieve CR. None underwent an allogeneic stem cell transplant in first CR. The median duration of CR was 81 months (range, 60–137). At the time of relapse, median WBC count was 4.4 x109/L (range 1.7–48.8). Karyotype at relapse was diploid in 2, del(5)del(7) in 1, del(6)del(7) in 1, trisomy 8 in 1, hyperdiploid in 2, add(2q) and add(6q) in 1 each and unavailable in 2 patients. The karyotype at relapse was different from the initial finding in 8 of 8 patients with available data at both time points. Treatment for relapse included Ida (or Dauno) with Ara-C in 8 patients (1 with additional fludarabine), and other agents in 3 patients. The response to treatment was CR in 4, partial remission in 2, resistant in 4 and unknown in 1. No patient underwent an allogeneic stem cell transplant in second CR. The median duration of the second CR was 2 months (range 0–37). The median survival after relapse was 6.4 months (range 1–39). Median survival from initial diagnosis of AML was 107 months (range 68–143). We conclude that late relapses in AML (>5 years after CR) are infrequent (1.16% of all relapses) and response to their subsequent therapy is poor; best responses occur with a regimen similar to the initial induction regimen. The karyotype at relapse is frequently different raising the question of a second AML versus relapse with the original clone.

Stem Cell Transplant Versus Chemotherapy in Older Adults with Acute Myelogenous Leukemia In First Remission

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2146-2146
Author(s):  
Ellin Berman ◽  
Molly Maloy ◽  
Sean M. Devlin ◽  
Esperanza B Papadopoulos ◽  
Ann A. Jakubowski
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Stem Cell ◽  
Cord Blood ◽  
Induction Chemotherapy ◽  
Acute Myelogenous Leukemia ◽  
Stem Cell Transplant ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Acute Myelogenous

Abstract Introduction Optimal therapy for older adults with acute myelogenous leukemia (AML) who achieve remission following induction chemotherapy has not been determined. Options include consolidation chemotherapy (CC) or stem cell transplant (SCT) if an appropriate donor is identified. In order to determine whether SCT improved overall survival (OS) or whether associated toxicity was increased, we performed a retrospective study comparing SCT with CC in this older age group. Methods All adult patients ages 60 to 75 years with AML in 1st remission (CR1) who underwent a SCT at MSKCC between 2001 and 2013 were reviewed and compared to age-matched patients with AML who achieved CR1 and received CC. A landmark analysis at 3 months following CR1 was used to compare OS for the 2 patient groups. Only SCT patients transplanted by landmark time were included in the analysis. Overall survival was compared using Kaplan-Meier methodology. Results Sixty-eight patients were identified for the SCT group. Thirty-two patients were identified for the CC group (Table). Stem cell sources included: peripheral blood (n=63), cord blood (n=4) and bone marrow (n=1). Fifty-six patients received a T cell depleted transplant (32 with ClinMACsTM and 24 with IsolexTM ) and 12 received an unmodified product. Conditioning regimens were busulfan/melphalan/ fludarabine (n=54), melphalan/fludarabine (n=4), cyclophosphamide/fludarabine/thiotepa/ TBI (n=4), fludarabine/busulfan (n=3), busulfan/melphalan (n=2) and thiotepa/fludarabine/TBI (n=1). Donors included matched unrelated (n=28), matched related (n=25), mismatched unrelated (n=11) and mismatched cord blood (n=4). For patients in the CC group, induction chemotherapy included cytarabine in combination with either idarubicin (n=21), daunorubicin (n=10), or mitoxantrone plus etoposide (n=1). Forty-four patients received their transplant by the 3 month landmark and 30 patients in the CC group were alive at the landmark and were included in the OS analysis. Deaths in the SCT group included 4 patients from infection, 1 from treatment-related toxicity, and 1 from relapsed disease. The estimated OS at 2 years in the landmark groups were 64% in the SCT group and 42% in the CC group (p=0.04). Conclusions Recognizing the inherent bias when retrospective studies compare SCT and CC, these data support the use of SCT for older patients with AML in CR1 who have an appropriate donor. Despite the older age, there was a statistically significant better OS with low 100 day mortality for those patients who underwent SCT. Disclosures: No relevant conflicts of interest to declare.

Phase I Study of Decitabine and Rapamycin in Relapsed/Refractory Acute Myelogenous Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3549-3549
Author(s):  
Jane L. Liesveld ◽  
Kristen O'Dwyer ◽  
Michael W. Becker ◽  
Deborah Mulford ◽  
Alison Walker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase I ◽  
Phase I Study ◽  
Stem Cell Transplant ◽  
Single Agent ◽  
Myelogenous Leukemia ◽  
Akt Pathway ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Acute Myelogenous

Abstract Abstract 3549 Introduction: Decitabine (5-aza-2'-deoxyctiidine) has demonstrated single agent activity in newly diagnosed acute myelogenous leukemia (AML). Complete response rates are low, however, and this agent has not been extensively studied in settings of relapsed or refractory disease where treatment responses are generally short in the absence of allogeneic stem cell transplantation. Most AML cases have activation of the mTOR pathway as evidenced by expression of phosphorylated p70S6 kinase or phopho-4EBP1. Since inhibitors of the mTOR pathway such as the tuberous sclerosis genes (TSC1 and TSC2) are hypermethylated in some cases of AML and there is evidence that decitabine may inhibit the PI3K/Akt pathway often activated after mTOR inhibition, we conducted a phase I study utilizing decitabine (DAC) followed by the mTOR inhibitor rapamycin in patients with relapsed/refractory AML to assess safety and feasibility. Methods: Patients ≥ 18 years of age with non-M3 AML with relapsed or refractory disease were eligible for this protocol. Patients who had relapsed after allogeneic stem cell transplant were eligible if they did not have active graft vs. host disease >grade 1 of skin. Patients received DAC 20 mg/m2 intravenously daily for 5 days followed by rapamycin from day 6 to 25 at doses of 2mg, 4mg, and 6 mg/day in a 3+3 dose escalation design. Cycles were 28 days in duration, and in the absence of overt progression of disease, patients could receive up to 6 cycles of therapy. A marrow aspirate was performed at day 5 to assess effects of single agent decitabine on mTOR and Akt pathway mediators. Bone marrow responses were assessed after cycles 1 and 3. Results: Thirteen patients were treated, and 12 are available for safety evaluation. The median age of patients is 64 years (range 46–78). Median marrow blast percentage at enrollment was 35% (range 6–83%). In the 2 mg dose cohort, 1 patient had disease progression before completion of cycle 1 and another patient in the first cohort had a history of prolonged neutropenia at the time of enrollment and experienced reversible grade 3 mucositis, which was deemed a DLT. Three more patients enrolled at this dose, and no further DLTs were observed, allowing dose escalation to the 4 mg and 6 mg cohorts. The MTD has not yet been reached. Reversible grade 2–3 mucositis occurred in 7 patients, but no other recurrent non-hematologic toxicities were seen. On the 2 mg cohort, all patients achieved therapeutic rapamycin levels (5–15 ng/ml) during the first cycle, and in 5/7 patients, the therapeutic level was achieved within 4 days of beginning rapamycin. In the 2 mg cohort, no cumulative increase in rapamycin levels occurred over subsequent cycles (4/7 completed >1 cycle). In the 4 mg cohort, one patient had an elevated level at day 9, and one patient on concomitant voriconazole had supra-therapeutic levels at day 16 and day 23. At the end of one cycle, 4 patients demonstrated disease progression, 5 had stable marrow blasts, and 4 demonstrated a decline in marrow blast percentage. Median survival to date is 6 months (range 1 to 15+ months). Two patients proceeded to allogeneic stem cell transplant, and one patient who relapsed shortly after stem cell transplant survived 4 months and demonstrated stable donor chimerism during that time. As assessed by Western blotting in 9 patients with evaluable samples at baseline, 87% of these cases expressed phospho (p)-4EBP1 at diagnosis, 56% p70S6K, 67% peIF4E, and 44% pAKT. In the 7 patients with Western blot samples evaluable at the end of cycle 1, 3 had decreases in p4EBP1 after the first cycle, and 4 had increased expression. Of the 7 evaluable patients, only 3 expressed baseline p70S6K, and this decreased in 2 and was unchanged in 1 patient. Conclusion: The combination of decitabine and rapamycin can be safely administered to patients with relapsed/refractory AML. Based on this phase I data, a phase II cohort to define efficacy can be conducted at the 2 mg rapamycin dosing given the therapeutic rapamycin levels demonstrated at this dose. Effects on mTOR mediators and on AKT can be serially assessed and are variable. Correlation with clinical response will require a phase II study. This trial is registered at clinical trials.gov as NCT00861874. Disclosures: Liesveld: Eisai: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Ariad: Honoraria. Off Label Use: This is a phase 1 study to see if rapamycin is safe in AML.

scholarly journals A Rare Case of Chronic Myelogenous Leukemia Presenting as T-Cell Lymphoblastic Crisis

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Parikshit Padhi ◽  
Margarita Topalovski ◽  
Radwa El Behery ◽  
Eduardo S. Cantu ◽  
Ramadevi Medavarapu
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Chronic Myelogenous Leukemia ◽  
Stem Cell Transplant ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant

Chronic Myelogenous Leukemia in blast crisis can manifest as either myeloid (more common) or lymphoid blast crisis. Most lymphoblastic crises are of B-cell lineage. T-cell blast crisis is extremely rare, with only a few reported cases. We present a case of a middle-aged man who was diagnosed with CML on peripheral blood and bone marrow biopsy. Because of a generalized lymphadenopathy noted at the time of diagnosis, a lymph node biopsy was also performed, which revealed a T-cell lymphoblastic leukemia/lymphoma, BCR/ABL1 positive, with clonal evolution. This is a very rare manifestation of CML in blast crisis with no standard treatment and with poor outcomes despite chemotherapy or allogeneic stem cell transplant. Given its rarity, it would be difficult to develop standard chemotherapy protocols. We believe the treatment for this condition should be similar to any lymphoid blast crisis. The patient was treated with induction chemotherapy (hyper-CVAD regimen) plus dasatinib for 3 cycles followed by sibling-donor allogeneic stem cell transplant and is currently on maintenance dasatinib and has minimal residual disease at this time.

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