R. Koós

Donor-cell myelodysplastic syndrome developing 13 years after marrow grafting for aplastic anemia

Donor-cell-derived hematopoietic malignancy is a rare event after bone marrow transplantation. Most cases in the literature occurred within the first year. We present a rare case of a female patient who had a bone marrow transplant for severe aplastic anemia (SAA) at the age of two and a half years from her human leukocyte antigen-identical brother. She developed a myelodysplastic syndrome (refractory cytopenia with multilineage dysplasia) 12 years later. Initially, the malignant clone was of recipient origin, but within several months, progression to a clinically more aggressive refractory anemia with excess blasts (RAEB) was accompanied by the outgrowth of a new clone of donor origin. In this report we provide evidence proving that the patients final malignant clone arose in donor cells: cytogenetic analysis of the marrow showed a male karyotype and a t(3;21)(q26;q21) in all 62 metaphases analyzed. Interphase fluorescence in situ hybridization showed that all identifiable cells contained the Y chromosome. We conclude that donor-cell-derived hematopoietic malignancy after bone marrow transplantation can occur even after many years. We believe that the 13 years that elapsed between the transplant and the development of RAEB in our case represent the longest latency period in the literature.

The investigation of late cytogenetic effects in children with acute leukaemia in long remission and off all chemotherapy

SummaryChromosome studies carried out using both “conventional” and “banding” techniques indicate that no late cytogenetic effects exist in patients who received complex cytostatic therapy for about three years and were off all treatment at the time of study. Sister chromatid exchange values that normally indicate mutagenic effects were similar to those of the normal controls. It was also found, however, that the cell cycle time of “remission lymphocyte populations” differs from the values of healthy controls.

Acid sphingomyelinase deficiency in Beckwith-Wiedemann syndrome

We report the association of Beckwith-Wiedemann syndrome (BWS) and a residual acid sphingomyelinase (ASM) activity of about 35% in a 23 months old Hungarian boy. Besides the classical triad of exomphalos, macroglossia and gigantism some other BWS-related features: polyhydramnios (known from the praenatal history), hemihypertrophy, craniofacial dysmorphy, a mild mental retardation, bilaterally undescended testes, cardiac anomalies and a terminally developed, fatal embryonal rhabdomyosarcoma were present in the patient. The decreased activity of the ASM was measured in the patient’s skin fibroblasts. This result, with hepatomegaly, mental retardation, feeding problems, a failure to thrive and musclehypotony, partially resembled the ASM-deficient forms of Niemann-Pick disease (NPD). Morphological analysis of the bone-marrow cells gave normal results. There was no chromosomal alteration found by conventional karyotyping of the patient’s lymphocytes.BWS-associated genes as well as the human ASM gene (SMPD1) are all located at 11p15. DNA-studies by region specific markers as well as mutational analysis for the most common NPD-mutations are planned in the future. This is the first report on the simultaneous occurrence of BWS and ASM-deficiency.

Hypophysenfunktion und Wachstum bei Kindern unter Leukämiebehandlung

Der Effekt von Rontgenbestrahlungen des Schadels mit Dosen von 2400 und 4800 rad auf die Hypophysenfunktion von Kindern mit akuter lymphoblastischer Leukamie wurde untersucht. Der STH-Spiegel im Plasma nach Arginin-Stimulation war bei diesen Kindern im Alter von 13 bis 15 Jahren normal, ebenso der TSH-Anstieg nach TRH-Stimulation und das Ergebnis des Metopiron-Tests. Schlieslich war das Wachstum von 40 solchen Kindern wahrend einer Beobachtungszeit von 3 oder mehr Jahren regelrecht.

Childhood Leukemia and Statistical Characteristics in 0- to 18-Year-Old Patients in Hungary, Diagnosed Between 1988 and 1992

A population-based cancer registry for childhood leukemia was started in Hungary in 1971. Data processing and analysis have been done at the Second Department of Pediatrics, Semmelweis University Medical School in Budapest, which is the main center for the treatment of childhood malignancies in Hungary. In 1992 a new computerized database structure was created in collaboration with Kansas University Medical Center, Kansas City, Kansas, United States. This work presents childhood leukemia frequency distribution and treatment results between 1988 and 1992 in Hungary. The number of patients diagnosed with leukemia under 18 years of age fluctuates between 69 and 82 cases per year. We present the main causes of death and outline our future objectives to improve the survival rate and quality of life.