Central nervous system (CNS) invasion was defined as more than 5 mononuclear cells per microliter of cerebrospinal fluid with obvious lymphoblasts. In patients with t(4;11)+ ALL, the detection of MRD with the polymerase chain reaction (PCR) was significantly related to outcome.48  Indeed, in our preliminary study, MRD was present after induction or intensification chemotherapy in most MLL+ patients (unpublished data, November 2003).

The normal MLL gene plays a key role in developmental regulation of gene expression (including HOX genes), and in leukemia this function is subverted by breakage, recombination, and chimeric fusion with one of 40 or more alternative partner genes. The MLL(mixed-lineage leukemia) gene, located on chromosome 11q23, is involved in chromosomal translocations in a subtype of acute leukemia, which represents approximately 10% of acute lymphoblastic leukemia and 2.8% of acute myeloid leukemia cases.

The intent was to perform transplantation in all patients in first remission preferentially within 3 to 5 months after diagnosis; however, those who had relapses before HSCT underwent the procedure at relapse or in second remission. Four patients had transplantation-related deaths due to sepsis, graft rejection, respiratory failure, or veno-occlusive disease of the liver (VOD)/thrombotic microangiopathy (TMA). reductions in the amount of cancerous tissue, and many remained disease-free When ... Carly Tobin loves dancing for the fun and freedom it provides. 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. Barker JN, Wagner JE. designed to break up the interaction by wedging itself between Menin and

MLL-rearranged B-ALL samples, while “closest” to B-ALL, were clustered together and separate from other B-ALL samples (see figure). Induction of graft-versus-host disease and a graft-versus-leukemia effect using ubenimex in a patient with infantile leukemia relapsing after an unrelated cord blood transplant. Okada H, Nomi K, Hamatani S, et al. doi: https://doi.org/10.1182/blood-2004-09-3504.

Prophylaxis for graft-versus-host disease (GVHD) consisted of either cyclosporin A (CSA) or FK506 (FK) combined with short-term methotrexate (MTX). While similar types of analysis have been performed previously,2-5  this is the largest study using well-annotated AML, T-ALL, and B-ALL samples and thus provides important new insight into the biology of these leukemias. Relapse occurred before HSCT in 11 patients and later in 7 (including 1 patient who failed to respond to induction therapy).

For all infants undergoing HSCT, less toxic conditioning regimens might be introduced without any appreciable loss of efficacy. Improved survival for acute lymphoblastic leukemia in infancy: the experience of EORTC-Childhood Leukemia Cooperative Group. Two subgroups in our study, patients younger than 6 months with high WBC counts (≥ 100 × 109/L) and those with CNS invasion at diagnosis, continued to fare poorly, indicating a need to consider more frequent intrathecal chemotherapy or intensified high-dose Ara-C therapy before HSCT for these patients. These results suggest that early introduction of HSCT, possibly with a less toxic conditioning regimen, may improve the prognosis for infants with MLL+ ALL. This makes for particularly aggressive disease, so the prognosis of MLL-r is often poor, especially in infants with ALL. The use of alloSCT in first CR does not

Prior to treatment, each patient was evaluated with respect to the characteristics of the leukemic cells, including immunophenotype, cytogenetics, and MLL gene rearrangement. Emminger W, Emminger-Schmidmeier W, Haas OA, et al. The resulting “fusion” proteins bind to chromatin – the long fibers in which DNA and related proteins are packaged – and disrupt the activity of genes. Risk-directed treatment of infant acute lymphoblastic leukemia based on early assessment of MLL gene status: results of the Japan Infant Leukemia Study (MLL96).


Reaman GH, Sposto R, Sensel MG, et al. and MLLT3 (formerly AF9; ∼15%). The 3-year posttransplantation EFS rate for the 29 patients who underwent HSCT in first remission was 64.4% (46.4%-82.4%).

Vassal G, Gouyette A, Hartmann O, Pico JL, Lemerle J. Pharmacokinetics of high-dose busulfan in children. Comparison of 3-year EFS rates by presenting features in infants with MLL+ ALL. A new study in mice and human cell lines, published this week by Cancer Cell, finds promise in a targeted, orally bioavailable compound that inhibits a key growth pathway in MLL-r leukemia. Thus, a major challenge for the future will be to confirm the efficacy of intensified chemotherapy for selected subgroup of infants.

Better, less toxic treatments are greatly needed.

Each patient was assigned to a subgroup according to the presence or absence of CD10 expression at diagnosis (CD10 negativity correlates closely with MLL gene rearrangement6 ).
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 × 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). A major concern with the use of HSCT in infants is the possibility of late adverse sequelae, including growth impairment.

The majority of patients in the current investigation underwent UCBT rather than UBMT, for the following reasons. But, gene expression studies performed on human tumors are largely hypothesis-generating experiments and thus much work lies ahead in the testing of these hypotheses.

Because it is possible that the patients undergoing HSCT in first remission had more favorable prognostic factors than others in the series, we compared selected clinical characteristics of these 2 groups. MLLr

Giralt S, Estey E, Albitar M, et al. associated with aberrant epigenetic programs. When Finn Beaulieu learned how to say elephant, he ran around the house repeating the word at least 20 times. However, as preliminary results, growth impairment has been reported by several investigators who registered patients in this study undergoing HSCT with a TBI-conditioning regimen (E. I., unpublished observations, April 2004). Finally, VTP50469 appeared to act only at specific When Ross et al performed unsupervised clustering of leukemia samples using principle component analysis, MLL-rearranged AMLs and T-ALLs were intermixed with the other AML and T-ALL samples, respectively. The dose of each drug except VCR was reduced by one third in patients younger than 2 months and by one fourth in those 2 to 4 months of age. They noted that patients given transplants earlier than 4 months after remission induction had a significantly better prognosis than those undergoing the procedure at later times. Cytogenetic analysis of leukemic cells was performed by a G-banding technique. The estimated rates at 3 years were 58.2% (95% CI, 43.5%-72.9%) and 43.6% (28.5%-58.7%), respectively.

Patients receiving transplants in first remission fared significantly better than those undergoing HSCT at other times (3-year posttransplantation EFS, 64.4% versus 22.2%, P = .004). Is 600 mg/m2 the appropriate dosage of busulfan in pediatric patients undergoing bone marrow transplantation? Stepwise multivariate analysis of posttransplantation EFS rates indicated independent predictive strength for remission status at HSCT (first remission versus other) in the context of age (younger versus older than 6 months at diagnosis), gender (male versus female), CNS invasion at diagnosis, initial WBC count (< 100 versus ≥ 100 × 109/L), and karyotype (4;11 translocation versus other; hazard ratio, 0.0268; P < .0001).

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