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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3527-3534.
Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2004-04-1390.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Infant acute lymphoblastic leukemia with MLL gene rearrangements: outcome following intensive chemotherapy and hematopoietic stem cell transplantation
Yoshiyuki Kosaka,
Katsuyoshi Koh,
Naoko Kinukawa,
Yoshihiro Wakazono,
Keiichi Isoyama,
Takanori Oda,
Yasuhide Hayashi,
Shigeru Ohta,
Hiroshi Moritake,
Megumi Oda,
Yoshihisa Nagatoshi,
Hisato Kigasawa,
Yasushi Ishida,
Akira Ohara,
Ryouji Hanada,
Masahiro Sako,
Takeyuki Sato,
Shuki Mizutani,
Keizo Horibe, and
Eiichi Ishii
From the Department of Hematology and Oncology, Hyogo Children's Hospital, Kobe, Japan; Department of Pediatrics, University of Tokyo, Tokyo, Japan; Department of Medical Information Science, Kyushu University, Fukuoka, Japan; Division of Pediatrics, Kyoto Katsura Hospital, Kyoto, Japan; Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Japan; Department of Pediatrics, Hokkaido Children's Hospital and Medical Center, Sapporo, Japan; Department of Hematology and Oncology, Gunma Children's Medical Center, Setagun, Japan; Department of Pediatrics, Shiga Medical School, Ohtsu, Japan; Department of Pediatrics, University of Miyazaki, Miyazaki, Japan; Department of Pediatrics, Okayama University, Okayama, Japan; Section of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan; Department of Hematology, Kanagawa Children's Medical Center, Yokohama, Japan; Department of Pediatrics, Ehime University, Onsengun, Japan; Department of Pediatrics, Toho University, Tokyo, Japan; Department of Hematology and Oncology, Saitama Children's Medical Center, Iwaki, Japan; Department of Pediatrics, Osaka City General Hospital, Osaka, Japan; Department of Pediatrics, Chiba University, Chiba, Japan; Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan; Clinical Research Center, National Nagoya Hospital, Nagoya, Japan; Department of Pediatrics, Saga University, Saga, Japan.
Forty-four infants with acute lymphoblastic leukemia (ALL) characterized by MLL gene rearrangements were treated on a protocol of intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT) between November 1998 and June 2002. The remission induction rate was 91.0%, and the 3-year overall survival and event-free survival (EFS) rates, with 95% confidence intervals, were 58.2% (43.5%-72.9%) and 43.6% (28.5%-58.7%), respectively. Univariate analysis of EFS by presenting features indicated a poorer outcome in patients younger than 6 months of age with high white blood cell counts ( 100 x 109/L; EFS rate, 9.4% versus 55.1% for all others, P = .0036) and in those with central nervous system invasion (EFS rate, 10.0% versus 56.9% for all others, P = .0073). The 3-year posttransplantation EFS rate for the 29 patients who underwent HSCT in first remission was 64.4% (46.4%-82.4%). In this subgroup, only the timing of HSCT (first remission versus others) was a significant risk factor by multivariate analysis (P < .0001). These results suggest that early introduction of HSCT, possibly with a less toxic conditioning regimen, may improve the prognosis for infants with MLL+ ALL. Identification of subgroups or patients who respond well to intensified chemotherapy alone should have a high priority in future investigations.
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