Toxicity and efficacy of intensive chemotherapy for children with acute lymphoblastic leukemia (ALL) after first bone marrow or extramedullary relapse.
BACKGROUND
Approximately 25% of children newly diagnosed with acute lymphoblastic leukemia (ALL) will eventually experience leukemic relapse, with bone marrow being the most common site of recurrence. The ability to achieve a durable second remission is complicated by toxicity and resistant disease. We report a novel combination of chemotherapy for relapsed pediatric ALL.


METHODS
Thirty pediatric patients with relapsed medullary (n = 18) and extra-medullary (n = 12) ALL were enrolled at three pediatric institutions. Following receipt of induction and the first Block A and Block B of intensification, each patient was evaluated for toxicity, efficacy in achieving remission, and long-term survival. Additionally, minimal residual disease (MRD) detection by multidimensional flow cytometry (MDF) was performed.


RESULTS
During induction, the major non-hematopoeitic toxicities were mucositis (30% of patients) and bacteremia (50% of patients). Two patients (7%) died of toxicity during induction. Toxicity during intensification Block 1A and 1B was markedly reduced. Eight-nine percent of patients with marrow disease achieved a remission following induction and intensification. The event-free survival (EFS) for all patients at 2 and 4 years were 60% (95% CI: 42-78%) and 49% (95% CI: 30-68%), respectively.


CONCLUSIONS
This regimen for patients with relapsed ALL was successful in achieving a second remission for the majority of patients with acceptable toxicity.
Thomson
Blythe
B
Seattle Children's Hospital and Regional Medical Center, Seattle, Washington, USA. blythe.thompson@seattlechildrens.org
Park
Julie R
JR
Felgenhauer
Judy
J
Meshinchi
Soheil
S
Holcenberg
John
J
Geyer
J Russell
JR
Avramis
Vassilios
V
Douglas
James G
JG
Loken
Michael R
MR
Hawkins
Douglas S
DS
D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D016470:Bacteremia / Q000139:chemically induced; D019046:Bone Marrow Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007069:Ifosfamide / Q000008:administration & dosage; D007223:Infant; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D009061:Mouth Mucosa / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D012008:Recurrence; D013280:Stomatitis / Q000139:chemically induced; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D011092:Polyethylene Glycols; D014750:Vincristine; D005047:Etoposide; C042705:pegaspargase; D003907:Dexamethasone; D001215:Asparaginase; D013866:Thioguanine; D015080:Mesna; D002955:Leucovorin; D007069:Ifosfamide; D008727:Methotrexate; D015255:Idarubicin