No abstract

During T cell selection in the thymic cortex more than 90% of the thymocytes are eliminated by apoptosis. Based on this biology, we propose to define blasts of T cell acute lymphoblastic leukemia (ALL) with the phenotype of cortical thymocytes (CD1 ؉ and/or CD4 ؉ 8 ؉ ) as selection-related (SR) and all other T-ALL immunophenotypes as non-selection-related (NSR). The COALL cooperative treatment studies for childhood ALL offer a tool to study the outcome in T-ALL subgroups as children with T-ALL are allocated uniformly to the high risk arm of the protocol. In the COALL-85, -89 and -92 protocols, 39/83 cases presented as SR and 44/83 cases as NSR. Five-year event-free survival of SR phenotype is significantly better compared to the NSR group (0.87 ± 0.06 vs 0.66 ± 0.07, log rank test, P = 0.01). T-ALL with SR phenotype is a distinct subgroup of leukemia with excellent prognosis under a high risk treatment protocol.

Metachromatic leukodystrophy refers to a group of genetic neurologic diseases caused by deficiencies of the enzyme arylsulfatase A and the resulting accumulation of sulfatides in white matter. Bone marrow transplantation has been advocated as a treatment in an attempt to correct the enzyme deficiency. Such a transplant was performed in 1991 in a 16-year-old girl with a form of late juvenile metachromatic leukodystrophy caused by a homozygous P426L mutation in the arylsulfatase A gene. Engraftment was prompt and resulted in constant enzymatic normalization of circulating lymphocytes. The elevated urinary excretion of sulfatides remained unaffected. Clinical findings up until transplantation consisted of gait disturbances, impairment of cognitive functioning, and deterioration in school performance over several years. During a 6-year follow-up period, the patient's condition was subject to major fluctuations but, on the whole, findings showed slow neurologic and neurophysiologic deterioration. The clinical course observed after bone marrow transplantation probably more or less reflects the natural course expected in this form of late-onset metachromatic leukodystrophy.

A 17-year-old woman was admitted for bone marrow transplantation with the diagnosis of atypical Philadelphia-negative chronic myelogenous leukemia (aCML), cytogenetically characterized by trisomy 8 as the sole chromosome aberration. A striking feature was a congenital opacity of the right cornea. Chromosomal analysis of skin fibroblasts were performed and revealed a mosaic for trisomy 8. Commonly, a distinct clinical picture leads to the diagnosis of trisomy 8 mosaicism syndrome (T8ms), but an extreme phenotypic variability has been observed. To our knowledge the development of an aCML in a patient with T8ms has not been reported. A review of the literature revealed that an association to other hematological disorders had been described in two cases. The question of whether our patient's aCML was a random event or not is discussed. The patient is now 24 months post transplant and shows no evidence of disease. Her Karnofsky score is 100%. We conclude that it might be worthwhile to look for an associated constitutional trisomy 8 mosaicism in all patients with trisomy 8 leukemia.

Contradictory data have been reported about the prognostic value of myeloid antigen co‐expression (My+) in childhood acute lymphoblastic leukaemia (ALL). In the present study the methyl thiazol tetrazoliumbromide (MTT) assay was used to compare the in vitro cytotoxicity of 14 drugs between 60 My+ (CD13+ and/or CD33+) and 107 My− ALL children at initial diagnosis. P‐glycoprotein (P‐gp), multidrug resistance‐associated protein (MRP), major vault protein/lung resistance protein (LRP) and the intracellular daunorubicin concentration were studied by flow cytometry. My+ ALL samples were significantly more resistant, i.e. between 1.1‐ and 2.9‐fold, to daunorubicin, doxorubicin, idarubicin, mitoxantrone, vincristine, 6‐thioguanine, 6‐mercaptopurine, teniposide, etoposide and ifosfamide compared with My− ALL samples. My− and My+ ALL did not significantly differ in sensitivity to prednisolone, dexamethasone, l‐asparaginase and cytarabine. Comparable results were found when only common and preB ALL cases were analysed. Drug resistance in My+ ALL was not related to increased expression of P‐gp, MRP or LRP compared with My− ALL (ratio My+/My−:P‐gp 0.8, MRP 1.0, LRP 1.1). Accumulation and retention of daunorubicin did not significantly differ between My− and My+ ALL cells (ratio My+/My−: accumulation 1.2, retention 1.3). Therefore the nature of drug resistance in My+ ALL remains unknown. The lack of prognostic value for My+ in childhood ALL may be explained by the responsiveness of My+ ALL to glucocorticoids, l‐asparaginase and cytarabine. In addition, the currently intensive treatment regimens may apply drug doses which are simply high enough to overcome the mild resistance to anthracyclines, mitoxantrone, vincristine, thio‐purines, epipodophyllotoxins and ifosfamide in childhood My+ ALL.