scholarly journals Low-Dose Interleukin-2 Immunotherapy Does Not Improve Outcome of Patients Age 60 Years and Older With Acute Myeloid Leukemia in First Complete Remission: Cancer and Leukemia Group B Study 9720

2008 ◽  
Vol 26 (30) ◽  
pp. 4934-4939 ◽  
Author(s):  
Maria R. Baer ◽  
Stephen L. George ◽  
Michael A. Caligiuri ◽  
Ben L. Sanford ◽  
Sandra M. Bothun ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Low Dose ◽  
Interleukin 2 ◽  
Random Assignment ◽  
Consolidation Chemotherapy ◽  
Group B ◽  
Leukemia Group ◽  
Disease Free ◽  
First Complete Remission ◽  
Acute Myeloid

Purpose Cancer and Leukemia Group B (CALGB) 9720 evaluated subcutaneous low-dose recombinant interleukin-2 (rIL-2) maintenance immunotherapy as a strategy for prolonging remission in older patients with acute myeloid leukemia (AML). Patients and Methods AML patients age 60 years and older in first complete remission after induction and consolidation chemotherapy were randomly assigned to no further therapy or a 90-day regimen of 14-day cycles of low-dose rIL-2, aimed at expanding natural killer (NK) cells, followed by 3-day higher doses aimed at activating cytotoxicity of expanded NK cells to lyse residual AML cells. All randomly assigned patients were included in an intention-to-treat analysis. Results A total of 163 (64%) of 254 patients who completed induction and consolidation chemotherapy on CALGB 9720 were randomly assigned to rIL-2 (n = 81) or no further therapy (n = 82); the most common reasons for lack of random assignment were patient refusal and relapse. Fifteen patients randomly assigned to rIL-2 never initiated it because of refusal, intercurrent medical problems, or relapse, and 24 patients initiated rIL-2 but stopped early because of toxicity or relapse. Grade 4 toxicities during rIL-2 therapy included thrombocytopenia (65%) and neutropenia (64%), and grade 3 toxicities included anemia (33%), infection (24%) and malaise/fatigue (14%). Forty-two patients (52%) randomly assigned to rIL-2 completed the full 90-day course. Patients in both arms had similar distributions of both disease-free (combined median = 6.1 months; P = .47) and overall survival (combined median = 14.7 months; P = .61) after random assignment. Moreover, the 42 patients who completed all planned therapy did not show prolongation of disease-free or overall survival. Conclusion Low-dose rIL-2 maintenance immunotherapy is not a successful strategy in older AML patients.

Abnormal Cytogenetics at Date of Morphologic Complete Remission Predicts Short Overall and Disease-Free Survival, and Higher Relapse Rate in Adult Acute Myeloid Leukemia: Results From Cancer and Leukemia Group B Study 8461

2004 ◽  
Vol 22 (12) ◽  
pp. 2410-2418 ◽  
Author(s):  
Guido Marcucci ◽  
Krzysztof Mrózek ◽  
Amy S. Ruppert ◽  
Kellie J. Archer ◽  
Mark J. Pettenati ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Free Survival ◽  
Group B ◽  
Leukemia Group ◽  
Disease Free ◽  
Acute Myeloid

Purpose As most patients with acute myeloid leukemia (AML) with morphologic complete remission (CR) ultimately relapse, better predictors for outcome are needed. Recently, Cheson et al suggested using cytogenetic remission (CRc) as part of the criteria for CR. To our knowledge, ours is the first relatively large study evaluating the usefulness of CRc attained immediately following induction chemotherapy. Patients and Methods We included AML patients treated on Cancer and Leukemia Group B front-line studies with cytogenetic samples obtained at diagnosis and at the first day of documented CR following induction. Patients with abnormal cytogenetics at diagnosis, and normal cytogenetics at CR (NCR; n = 103) were compared with those with abnormal cytogenetics both at diagnosis and at CR (ACR; n = 15) for overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR). Cox proportional hazards models determined the prognostic significance of cytogenetics at CR, adjusting for other covariates. Results Clinical features were similar for both groups, with the exception of favorable cytogenetics [t(8;21), inv(16)/t(16;16), t(15;17)] at diagnosis, which was more frequent (P = .03) in the NCR group. Median follow-up was 3.1 years (range, 1.0 to 11.4 years). ACR patients had significantly shorter OS (P = .006) and DFS (P = .0001), and higher CIR (P = .0001). In multivariable models, the NCR and ACR groups were predictors for OS (P = .03), DFS (P = .02), and CIR (P = .05). The relative risk of relapse or death was 2.1 times higher for ACR patients than for NCR patients (95% CI, 1.1 to 3.9). Conclusion Our data suggest that converting to normal karyotype at the time of first CR is an important prognostic indicator and support the use of CRc as a criterion of CR in AML.

scholarly journals Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study

Blood ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 5164-5167 ◽  
Author(s):  
Susan P. Whitman ◽  
Amy S. Ruppert ◽  
Guido Marcucci ◽  
Krzysztof Mrózek ◽  
Peter Paschka ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Disease Free Survival ◽  
Partial Tandem Duplication ◽  
Group B ◽  
Leukemia Group ◽  
Disease Free ◽  
Acute Myeloid

AbstractThe clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808. Twenty-four (10.1%) patients harbored an MLL-PTD. Of those, 92% achieved complete remission (CR) compared with 83% of patients without MLL-PTD (P = .39). Neither overall survival nor disease-free survival significantly differed between the 2 groups (P = .67 and P = .55, respectively). Thirteen MLL-PTD+ patients relapsed within 1.4 years of achieving CR. MLL-PTD+ patients who relapsed more often had other adverse CN-AML–associated molecular markers. In contrast with previously reported studies, 9 (41%) MLL-PTD+ patients continue in long-term first remission (CR1; range, 2.5-7.7 years). Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD.

scholarly journals Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1224-1232 ◽  
Author(s):  
Maria R. Baer ◽  
Stephen L. George ◽  
Richard K. Dodge ◽  
Kieran L. O'Loughlin ◽  
Hans Minderman ◽  
...  
Keyword(s):  
Older Patients ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Phase 3 ◽  
Free Survival ◽  
Psc 833 ◽  
Group B ◽  
Leukemia Group ◽  
Disease Free ◽  
Acute Myeloid

The Cancer and Leukemia Group B conducted a phase 3 trial of the P-glycoprotein modulator PSC-833 in untreated acute myeloid leukemia patients aged 60 years and older. Patients were randomized to 1 of 2 regimens, with doses determined in a prior phase 1 study, consisting of cytarabine 100 mg/m2/d by 7-day infusion, with daunorubicin 60 mg/m2 and etoposide 100 mg/m2 daily for 3 days (ADE), or daunorubicin 40 mg/m2 and etoposide 60 mg/m2 for 3 days with PSC-833, 2.8 mg/kg over 2 hours, and then 10 mg/kg/d by 3-day infusion (ADEP). The ADEP arm was closed after randomization of 120 patients (61 to ADE and 59 to ADEP) because of excessive early mortality. Rates of complete remission, nonresponse, and death were 46%, 34%, and 20% for ADE, versus 39%, 17%, and 44% for ADEP (P = .008). Nevertheless, disease-free survival (median 7 vs 8 months; P = .38) and overall survival (approximately 33% alive at 1 year) did not differ and were similar to historical results. Although the number of patients was limited, ADE patients whose pretreatment cells exhibited PSC-833–modulated dye efflux in vitro (n = 22) had worse outcomes than those without efflux (n = 11) (complete remission, nonresponse, and death rates of 41%, 41%, and 18%, compared with 91%, 9%, and 0%; P = .03), but with ADEP outcomes were nearly identical. Moreover, for patients with PSC-833–modulated efflux, median disease-free survival was 5 months with ADE and 14 months with ADEP (P = .07). Further modulation trials in older patients must await the design of less-toxic regimens.

scholarly journals FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study

Blood ◽  
2010 ◽  
Vol 116 (18) ◽  
pp. 3622-3626 ◽  
Author(s):  
Susan P. Whitman ◽  
Kati Maharry ◽  
Michael D. Radmacher ◽  
Heiko Becker ◽  
Krzysztof Mrózek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Microrna Expression ◽  
Free Survival ◽  
Group B ◽  
Leukemia Group ◽  
Disease Free ◽  
Acute Myeloid

Abstract The clinical impact of FLT3-internal tandem duplications (ITDs), an adverse prognostic marker in adults aged < 60 years with primary cytogenetically normal acute myeloid leukemia (CN-AML), requires further investigation in older patients. In CN-AML patients aged ≥ 60 years treated on Cancer and Leukemia Group B frontline trials, we found that FLT3-ITD remained associ-ated with shorter disease-free survival (P < .001; hazard ratio = 2.10) and overall survival (P < .001; hazard ratio = 1.97) in multivariable analyses. This impact on shorter disease-free survival and overall survival was in patients aged 60-69 (P < .001, each) rather than in those aged ≥ 70 years. An FLT3-ITD–associated gene-expression signature revealed overexpression of FLT3, homeobox genes (MEIS1, PBX3, HOXB3), and immunotherapeutic tar-gets (WT1, CD33) and underexpression of leukemia-associated (MLLT3, TAL1) and erythropoiesis-associated (GATA3, EPOR, ANK1, HEMGN) genes. An FLT3-ITD–associated microRNA-expression signature included overexpressed miR-155 and underexpressed miR-144 and miR-451. FLT3-ITD identifies older CN-AML patients with molecular high risk and is associated with gene- and microRNA-expression signatures that provide biologic insights for novel therapeutic approaches.

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