Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia.
OBJECTIVE
Only 20-30% of elderly patients with acute lymphoblastic leukemia (ALL) are enrolled in clinical trials because of co-morbid disorders or poor performance status. We present the results of treatment of Philadelphia chromosome-negative (Ph-) ALL patients over 55 yr treated in the PETHEMA ALL-96 trial.


METHODS
From 1996 to 2006, 33 patients > or = 55 yr with Ph- ALL were included. Induction therapy was vincristine, daunorubicin, prednisone, asparaginase, and cyclophosphamide over 5 weeks. Central nervous system (CNS) prophylaxis involved triple intrathecal (IT) therapy, 14 doses over the first year. Consolidation-1 included mercaptopurine, methotrexate, teniposide and cytarabine, followed by one consolidation-2 cycle similar to the induction cycle. Maintenance consisted of mercaptopurine and methotrexate up to 2 yr in complete remission (CR) with monthly reinduction cycles (vincristine, prednisone and asparaginase) during the first year.


RESULTS
Median (range) age was 65 yr (56-77). Phenotype (30 patients): early-pre-B 7, common/pre-B 18, T 5. Cytogenetics (28 patients): normal 12, complex 10, t(4;11) 2 and other 4. CR was achieved in 19/33 (57.6%) patients, early death occurred in 12 (36.4%) and 2 (6%) were resistant. Overall survival and disease-free survival probabilities (2 yr, 95% CI) were 39% (21%-57%) and 46% (22%-70%), respectively (median follow up of 24 months). Removal of asparaginase and cyclophosphamide from the induction decreased induction death (OR 0.119, CI 95% 0.022-0.637, P = 0.013) and increased survival (20% vs. 52%, P = 0.05).


CONCLUSIONS
The prognosis of elderly Ph- ALL patients is poor. In this study, less intensive induction decreased toxic death, allowing delivery of planned consolidation therapy and increased survival probability.
Sancho
Juan-Manuel
JM
Clinical Hematology Department, Institut Catalá d'Oncologia-Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Ribera
Josep-Maria
JM
Xicoy
Blanca
B
Morgades
Mireia
M
Oriol
Albert
A
Tormo
Mar
M
del Potro
Eloy
E
Debén
Guillermo
G
Abella
Eugenia
E
Bethencourt
Concepción
C
Ortín
Xavier
X
Brunet
Salut
S
Ortega-Rivas
Fernando
F
Novo
Andrés
A
López
Ramón
R
Hernández-Rivas
Jesús-María
JM
Sanz
Miguel-Angel
MA
Feliu
Evarist
E
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D015897:Comorbidity; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D012074:Remission Induction; D012720:Severity of Illness Index; D016019:Survival Analysis; D013713:Teniposide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D003907:Dexamethasone; D003520:Cyclophosphamide; D013713:Teniposide; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin