Charles Ye

Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow morphology

Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency and by complex neurologic symptomatology including ataxia, developmental delay, and spasticity. Herein we report severe marrow dysplasia in a patient with PNP deficiency. Drug-related marrow dysfunction was unlikely, and marrow virological studies were negative. A preleukemic myelodysplastic syndrome was also unlikely due to normal marrow CD34+ cells, colony growth in clonogenic assay of marrow mononuclear cells, apoptosis rate, and Fas expression on marrow nucleated cells, as well as morphologic improvement of the marrow dysplasia after normal red blood cell transfusion. The patients marrow stroma showed hypersensitivity to irradiation and undetectable PNP enzyme activity similar to peripheral lymphocytes. This is the first report of PNP deficiency associated with increased lymphocyte and marrow stromal sensitivity to irradiation. We conclude that marrows from patients with PNP deficiency might have hypersensitivity to irradiation and can develop dysplastic morphology, caused either directly or indirectly by the inherited enzymatic defect.

Late-appearing Philadelphia chromosome in childhood acute myeloid leukemia.

A 3‐year‐old female was diagnosed with acute myeloid leukemia (AML‐M2). The disease was refractory to various chemotherapeutic agents. Cytogenetic analysis revealed a clone with trisomy 8 at diagnosis that was replaced by a clone containing a t(11;15) and del(20q) by the end of the second induction. A new clone, characterized by a Philadelphia chromosome, with the minor BCR/ABL p190 transcript, emerged 14 months after diagnosis and remained to the end of disease course. The late occurrence of the Philadelphia chromosome in AML has been documented rarely in adults. Pediatr Blood Cancer 2008;50:1052–1053.

Leptomeningeal precursor B-cell lymphoblastic lymphoma in a child with minimal bone marrow involvement.

The authors report an unusual presentation of a leptomeningeal lymphoblastic lymphoma in a 6-year-old boy with headache and papilledema as the only initial manifestations. The diagnosis was confirmed by the presence of precursor B-cell lymphoblasts in the cerebrospinal fluid, with no cerebral mass and with only 9% phenotypically identical blasts in the bone marrow. This patient was treated on a high-risk ALL protocol with intensive systemic/intrathecal chemotherapy plus cranial irradiation, and he remained in complete remission 6 months after his initial diagnosis.

Interphase cytogenetic analysis of clonality in peripheral blood cells from a patient with Down syndrome and acute megakaryoblastic leukemia

A combination of fluorescence-activated cell sorting and interphase fluorescence in situ hybridization (FISH) techniques was used to detect a clonal chromosomal marker in blasts, granulocytes, and T and B lymphocytes of the peripheral blood from a patient with Down syndrome and acute megakaryoblastic leukemia (AMKL) associated with trisomy 8 as a karyotypic abnormality. Immunophenotypic studies with flow cytometry showed two populations of leukemic blasts distinguished by their expression of the CD34 antigen. Interphase FISH studies revealed clonal trisomy 8 FISH signals in almost all blast cells, regardless of CD34 expression, as well as in a small subpopulation of granulocytes. Normal chromosome 8 signal patterns were detected in T and B cells and in a great majority of granulocytes. The present study provides evidence for the clonal involvement of leukemic blasts in AMKL of Down syndrome, indicating that a trisomy 8 abnormality may be a primary event in leukemogenesis. The transformation occurs in progenitor cells with limited myeloid differentiation and without involvement of lymphoid lineage cells.

Florid bone marrow haematogones in a child following treatment for acute lymphoblastic leukaemia

A 3-year-old boy was diagnosed with precursor B-cell acute lymphoblastic leukaemia in September 2000. His complete blood count showed WBC 81Æ9 · 10/l, haemoglobin concentration 73 g/l and platelet count 17 · 10/l. Circulating blasts accounted for 89% of the total white cells. The bone marrow was heavily populated by moderately sized blasts with a variable amount of light-blue cytoplasm. Neither cytoplasmic granules nor Auer rods were seen. The nuclei were often indented or clefted, with finely dispersed chromatin with or without prominent nucleoli (left). On flow cytometry, the blasts were positive for CD10, CD19, CD22, HLA-DR and terminal deoxynucleotidyl transferase (TdT), and negative (< 20%) for CD20 and cytoplasmic l chain. Cytogenetic analysis on the bone marrow aspirate yielded a low level of hyperdiploid cells. No reciprocal translocation was identified. The patient was treated with combination chemotherapy and remained in bone marrow remission thereafter. Two years after diagnosis he presented with an isolated central nervous system (CNS) relapse while on maintenance therapy. A second CNS remission was achieved within 2 weeks of starting ‘salvage’ therapy. During maintenance therapy, he experienced numerous episodes of transient, yet profound, trilineage myelosuppression necessitating intermittent interruptions in therapy. Examination of the bone marrow aspirate 1 month after completing therapy showed a population of immature lymphoid cells constituting approximately 40% of the total nucleated cells. These cells were small or intermediate in size, had a high nuclear:cytoplasmic ratio and a fine chromatin pattern. The nuclei were round or oval and lacked nucleoli (right, arrowheads). On flow cytometry, these cells (41% of total events) were positive for CD10, CD19, CD20, CD22, HLA-DR and cytoplasmic l chain, and negative (<20%) for TdT. No clonal lymphoid proliferation was evidenced on gene rearrangement studies by polymerase chain reaction. These immature lymphoid cells were deemed haematogones. The patient received no additional treatment. The disease remains in morphological and immunophenotypic remission, with fewer haematogones on the most recent bone marrow aspirate performed two months later. Such numerous haematogones are uncommon following chemotherapy and may pose diagnostic challenges.