Dialysis was performed for tumor lysis syndrome before induction therapy was administered. Complete remission was achieved after B-precursor ALL induction therapy with prednisolone, vincristine, and doxorubicin. The consolidation therapy was adapted from a regimen for advanced Burkitt lymphoma, according to the Japan Pediatric Leukaemia/Lymphoma Study Group B-NHL 03 advanced-stage protocol, including 6 courses of prednisolone, vincristine, cyclophosphamide, methotrexate, pirarubicin, and etoposide. Rituximab was combined with the chemotherapy in last 2 courses. This patient has been in remission for 2 years.
B-ALL with a precursor B-cell immunophenotype has been shown to occur in approximately 0.1% of children with ALL, and a chromosomal analysis to detect t(8;14) is required for a correct diagnosis of B-ALL.1–6 Almost all patients suffering B-ALL with a precursor B-cell immunophenotype are administered induction therapy for B-cell ALL, and after a correct diagnosis is made, consolidation chemotherapy for B-ALL is commenced.4,6,8,9 It is unclear whether the progression of B-ALL with a precursor B-cell immunophenotype is worse than that of B-ALL, but because B-ALL is responds well to treatment, B-ALL with a precursor B-cell immunophenotype is expected to behave similarly.
Chromosomal aberrations in addition to t(8;14) are often present in B-ALL, most commonly affecting chromosomes 1, 6, 7, 13, 17, and 22. The most frequent additional aberration involves the long arm of chromosome 1, typically as partial tetrasomy of 1q.2,7,10 The partial tetrasomy of 1q observed in our patient was caused by the inversion and insertion of chromosomal region 1q21.1 to 1q32.1 between 1q32.1 and 1q11. To the best of our knowledge, B-ALL with this partial tetrasomy of 1q, der(1)(pter → q32.1:: q32.1 → q21.1::q11 → qter), has not previously been reported.
Over 60% of the patients diagnosed with B-ALL and additional aberrations of chromosome 1 relapse or die.2,7,10 In our patient, the partial tetrasomy of 1q arose from the inversion of chromosomal region 1q21.1 to 1q32.1. The duplication of 1q21.1 has been reported in neuroblastoma,11 and the development of familial nonmedullary thyroid cancer has been linked to the distribution of 1q21.1.12 The wide variety of lymphomas associated with an abnormality of 1q21.1 has been also reported, including Burkitt lymphoma.2,10,13–20 It is interesting that malignant neoplasms with 1q21.1 confer poor prognoses. These facts suggest that our patient also has a poor prognosis. However, the partial tetrasomy of 1q involved the chromosomal region from 1q21.1 to 1q32.1, which was not only inserted but also inverted in our patient. We also speculate that the inverted chromosomal region 1q21.1 to 1q32.1 may act as an antisense molecule. The antisense molecule may induce different prognosis compared with malignant neoplasms with 1q21.1.
Based on our hypothesis and the fact that B-ALL with more than 3 cytogenetic abnormalities confers a poor prognosis,7 rituximab was added to the consolidation therapy for B-ALL in our patient to ensure a good outcome.21 The patients have been in complete remission for 3 years since chemotherapy. We also think that stem-cell transplantation would be an effective intervention, but has not been available to our patient because no human leukocyte antigen (HLA)-matched donor has been found.
We are grateful for the help of Dr. Toshiyuki Yamamoto, Graduate of Medicine at Tokyo Women's Medical University, for the array-based comparative genomic hybridization analysis.
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