Risk Groups in a Multicenter Pilot Study for Treatment of Acute Lymphoblastic and Acute Undifferentiated Leukemia in Adults

Hoelzer, Dieter; Thiel, Eckhard; Löffler, Helmut; Bodenstein, H.; Büchner, Th.; Engelhardt, R.; Ganser, Arnold; Messerer, D.; Rühl, H.; Zwingers, Thomas

doi:10.1007/978-3-642-70385-0_10

Cited by 69 publications

(115 citation statements)

References 5 publications

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“…Our results confirm that age is a major prognostic factor in ALL and that prognosis is poor in elderly ALL patients, both when achievement of CR and overall survival are considered (Bassan et al, 1996;Delannoy et al, 1990;Ferrari et al, 1995;Hoelzer et al, 1988;Gaynor et al, 1988;Hussein et al, 1989;Kantarjian et al, 1994;Taylor et al, 1992). In these studies the percentage of CR ranged from 11% to 65% (43% in our study), and the median survival ranged from 1 to 10 months (12 months in our study) (Table IV).…”

Section: Discussionsupporting

confidence: 74%

Prognostic factors in elderly acute lymphoblastic leukaemia

Legrand¹,

Marie

Marjanovic³

et al. 1997

Br J Haematol

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Summary.A retrospective study was performed on 46 unselected acute lymphoblastic leukaemia (ALL) elderly patients aged 60 years or more. Only 50% of these patients were included in the EORTC cooperative clinical trials, thus confirming the important selection bias in most of the published series on elderly ALL patients. 43% of the elderly patients achieved a complete remission (CR). The median survival was 10 months and the 5-year overall survival was only 7 : 6 Ϯ 4%. In multivariate analysis, W.H.O. performance status and peripheral blast counts at day 7 were found to significantly influence achievement of CR and survival. In patients with W.H.O. performance status у2, 35% died during induction treatment versus 4% in patients with W.H.O. performance status < 2. Patients > 70 years old showed a marked drop of the CR rate (27%) compared to those aged 60-69 (67%), and a very high death rate during the induction period (38% versus 4%). This suggests that ALL protocol treatments should be proposed until 70 years in patients with good-performance status, whereas less intensive treatment should be offered to elderly patients with performance status у2 and/or age у70. Peripheral blast counts at day 7 may help to adjust the treatment during induction phase.

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Section: Discussionsupporting

confidence: 74%

Prognostic factors in elderly acute lymphoblastic leukaemia

Legrand¹,

Marie

Marjanovic³

et al. 1997

Br J Haematol

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“…[1][2][3] Fewer than 50% of patients, however, are alive 5 years from diagnosis, with the majority of deaths being due to relapsed disease. 3,4 Survival following ALL relapse is dismal, 5 thus a key improvement in outcome may result from optimization of postremission consolidation therapy. Myeloablative conditioned (MAC) allo-SCT improves survival in patients in CR1 in both Ph-positive and negative disease, 6 due to a reduction in the relapse incidence (RI).…”

Section: Introductionmentioning

confidence: 99%

Evidence for a GVL effect following reduced-intensity allo-SCT in ALL: a British Society of Blood and Marrow Transplantation study

Medd

Peniket

Littlewood

et al. 2013

Bone Marrow Transplant

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Myeloablative allo-SCT decreases relapse incidence (RI) in ALL. Reduced intensity conditioning (RIC) may extend allo-SCT to older and less fit patients. Sixty-nine ALL patients reported to the BSBMT underwent fludarabine-based RIC allo-SCT, 38 from unrelated donors (UD). Forty-four patients received alemtuzumab. ALL was in CR in 64 patients (93%). This was a second or third SCT in 23 patients. Two-year OS and PFS were 36% and 32%, respectively. In multivariate analysis male recipients demonstrated better OS and PFS (hazard ratio (HR) ¼ 0.42, P ¼ 0.008 and HR ¼ 0.45, P ¼ 0.012, respectively). Two-year TRM was 29%: higher with younger age (HR ¼ 0.97/year, P ¼ 0.041), female recipient (HR ¼ 2.55, P ¼ 0.049) and increasing grade of acute GVHD (HR ¼ 1.87, P ¼ 0.001). Two-year RI was 38% and was lower in patients with acute and chronic GVHD (HR ¼ 0.62 per increasing grade, P ¼ 0.035 and HR ¼ 0.52, P ¼ 0.025, respectively). Long-term ALL-free survival is achievable following fludarabine-based RIC allo-SCT. The association between GVHD and decreased RI suggests the presence of a GVL effect.

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“…The disease risk stratification was based upon age, cytogenetics and the time taken to attain CR; 2 a modification of the classification proposed by Hoelzer et al 20 The following factors were analyzed in Cox proportionalhazards regression models: disease risk (standard versus intermediate versus high), gender, CR transplantation interval (o4 versus X4 months), type of induction therapy (UKALL X or similar versus UKALL XII or similar) and the leukocyte count at presentation (o30 versus X30 Â 10 9 /l). The effect of the intensity of maintenance therapy, in all 100 patients as well as only in the 86 alive and in CR 4 months after transplantation, was examined as follows: 0 versus 1 versus 2 versus 3 agents, and 0/1 agent versus 2/3 agents.…”

Section: Discussionmentioning

confidence: 99%

“…Seven patients received marrow that was purged in vitro with Campath-1M. 20 The first seven blood stem cell recipients received G-CSF (filgrastim) at the dose of 125 mg/m 2 s.c. twice a day for 7 days, and underwent leukapheresis on days 5-8 (4 consecutive days). They also had back-up autologous marrow collected (which was not used).…”

Section: Induction Chemotherapymentioning

confidence: 99%

The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients

Sirohi

Powles

Treleaven

et al. 2008

Bone Marrow Transplant

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A total of 100 adults with ALL in first CR received melphalan (110 mg/m 2 ) with TBI followed by autologous marrow (n ¼ 35) or single-agent melphalan (200 mg/m 2 ) followed by autologous blood stem cells (n ¼ 65). After adequate hematologic recovery, maintenance chemotherapy with 6-mercaptopurine, methotrexate and vincristine-prednisone was administered for 2 years. Six patients, all TBI recipients (P ¼ 0.001), died of toxicity. In total 70 patients received 6-mercaptopurine, 53 received methotrexate and 40 received vincristine-prednisone. The cumulative incidence of relapse at 7 years was 45%. The 7-year probabilities of disease-free survival (DFS) and overall survival were 45 and 48%. Age 30 years, 44 weeks to attain remission, and karyotypes t(4;11) and t(9;22) were associated with adverse outcome. Patients with 0 (standard risk), 1 (intermediate risk), and 2-3 (high risk) adverse features had 7-year cumulative incidences of relapse of 19, 53 and 82% (Po0.0001), and 7-year DFS probabilities of 73, 36 and 7% (Po0.0001). The 7-year probabilities of DFS for patients receiving 0, 1, 2 and 3 maintenance chemotherapy agents were 15, 29, 58 and 61% (Po0.0001). Maintenance chemotherapy intensity was an independent determinant of outcome in Cox analysis. Maintenance chemotherapy after autotransplantation reduces relapse and improves outcome in adult patients with ALL.

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Risk Groups in a Multicenter Pilot Study for Treatment of Acute Lymphoblastic and Acute Undifferentiated Leukemia in Adults

Cited by 69 publications

References 5 publications

Prognostic factors in elderly acute lymphoblastic leukaemia

Prognostic factors in elderly acute lymphoblastic leukaemia

Evidence for a GVL effect following reduced-intensity allo-SCT in ALL: a British Society of Blood and Marrow Transplantation study

The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients

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