[Congenital leukaemia and transient myeloproliferative disorder: diagnostic difficulties--case reports]. / Wrodzona bialaczka i przemijajacy zespól mieloproliferacyjny: trudnosci diagnostyczne--opis przypadków.

Congenital leukaemia occurs in only 0.8% of all cases of leukaemia in children. Despite great progress in the treatment of childhood leukaemia, prognosis is still poor. This type of leukaemia must be distinguished from leukaemic reactions and transient myeloproliferative disorder. Transient myeloproliferative disorder is a rare condition in the neonatal period, connected with trisomy or other abnormalities of chromosome 21. It is characterized by high blastosis in peripheral blood and bone marrow and it usually resolves without specific therapy in 1 to 3 months. We present two cases: congenital leukaemia and transient myeloproliferative disorder. The first patient was a boy in whom congenital myelomonoblastic leukaemia (M4 in FAB classification) was diagnosed at age of 6 weeks. He was treated according to BFM-96 for acute myeloblasts leukaemia protocol, but there was no remission and he died of progressive congenital leukaemia after 4 months. The second patient was a female neonate with Down's syndrome and a cardiac defect (common atrioventricular canal) in whom hyperleukocytosis with blastosis in peripheral blood and bone marrow were detected at 2 days of age. Although no specific antileukaemic therapy was given her condition improved. At age of 3 months we observed normalisation of peripheral blood and at 5 months of age the bone marrow smear was normal. These cases confirm the difficulties in differentiation between congenital leukaemia and transient myeloproliferative disorder presented in literature. In spite of the same haematological symptoms the only difference may be detection of nonhematopoietic tissue infiltration (skin and central nervous system) commonly occurring in congenital leukaemia or the presence of trisomy and other abnormalities of chromosome 21 in transient myeloproliferative disorder.

Clinico-hematological profile of congenital leukemia.

Congenital leukemia is a rare disorder that usually presents with extramedullary infiltrates and myeloid phenotype in 80% cases. The authors present 4 cases of congenital leukemia diagnosed over 11 year period, three of which were of acute lymphoid leukemia and one was of biphenotypic leukemia.

Karyotype evolution in a patient with biphenotypic neonatal leukemia.

We present the case of a 4-day-old boy with acute lymphoblastic leukemia showing at onset a karyotype 46,XY,t(4;11)(q21;q23). At relapse an additional change, add(2), was present. Molecular analysis showed the same immunoglobulin rearrangement both at onset and at relapse, but immunohistochemical analysis revealed some cells having myeloid features. A continuous cell line derived from the leukemic blasts of the patient presented typical monoblastic features.

More than two immunoglobulin heavy chain J region genes in the majority of infant leukemia.

Congenital and infant leukemia are rare conditions associated with a very poor prognosis due to the high frequency of adverse clinical and laboratory parameters. As the occurrence of multiple immunoglobulin heavy chain hybridization band in childhood leukemia has been associated with poor prognosis, we studied whether it was present in this type of leukemia as well. Seven cases were examined, 4 of them less than 7 months of age. The immunophenotype was lymphoid in 5 and hybrid in 2. Most had abnormal karyotypes. In 5 of the 7, including all with congenital leukemia, an immunoglobulin heavy chain J region multiband pattern was found by Southern blot. The multiband pattern, whether primary or due to clonal evolution, seems to be associated with poor prognosis.

Severe hypertensive reactions to teniposide (VM-26) in infants with congenital leukemia.

Two cases of infants with congenital leukemia who had severe, refractory hypertensive reactions to teniposide (VM-26) are described. Patients on a 5 mg/kg twice weekly schedule of teniposide had hypertensive reactions in which their systolic blood pressure was greater than 200 mm Hg after the second dose of teniposide. Hypertension combined with myelosuppression resulted in the patient's death in one case. Although the exact mechanism of this unusual toxicity of teniposide remains unknown, it might be an age-specific problem, considering the very young age of our patients. Meticulous monitoring of vital signs, including blood pressure, is mandatory in leukemic infants receiving teniposide.

Reciprocal translocation (11;19)(q23;p13) in congenital acute lymphoblastic leukemia.

The cytogenetic, clinical, and immunologic findings ina 4-month-old girl with acute lymphoblastic leukemia (ALL) are reported. The malignant lymphoblasts were characterized cytogenetically by the reciprocal translocation t(11;19)(q23;p13); immunologically by an immature pre-B-ALL phenotype. In spite of the high-risk nature of the leukemia, the patient attained complete remission relatively quickly and is still free of disease 3 years after diagnosis. Because the only two previously reported ALL patients with t(11;19) also seem to have responded well to therapy, this cytogenetic abnormality might turn out to be an indicator of favorable prognosis in ALL.

A case of congenital lymphoblastic leukemia: clinical course and significance of ultrasonography.

A case of congenital leukemia in which texture changes in ultrasonography were followed up is reported. The patient was a male infant hospitalized on day 22 after birth with multiple bluish skin nodules. Complete remission was achieved easily, but he relapsed early and died from the disease after six months. Because of L1 morphology the disease was classified as acute lymphoblastic leukemia, but the leukemic cells lacked the characteristics of lymphoid lineage on cytochemical, cytogenetic, immunological, and enzymological examination. Ultrasonography was considered a useful tool in the following respects for the treatment of the patient with congenital leukemia: The texture of the infiltration of leukemic cells into the liver was clearly visualized and changes in the images could be traced both in size and in number; the process of ventricular dilatation and brain atrophy were successively visualized.

Congenital acute lymphocytic leukemia in a newborn with Klinefelter syndrome.

A patient with congenital acute lymphocytic leukemia and Klinefelter syndrome is described. The abnormal karyotype appeared in both unstimulated lymphoblasts and stimulated remission lymphocytes. A buccal smear confirmed the presence of extra chromatin material. Klinefelter syndrome has not been described in congenital acute lymphocytic leukemia.

Congenital acute lymphoblastic leukemia with chromosomal abnormalities including a translocation (1;4;22).

Cytogenetic studies in a patient with inborn ALL demonstrated identical and complex abnormalities in all the cells, indicating a monoclonal origin. These abnormalities included, among others, a translocation (1;4;22).

Cytogenetic findings in congenital leukemia: case report and review of the literature.

The cytogenetic findings in a five-week-old female infant with acute lymphoblastic leukemia (ALL) are reported. Markers 11q - and 19 + were observed and considered to be due to an interstitial deletion of segment 11q13 to 11q23 of chromosome #11 and an insertion of this segment into the terminal region of the short arm of #19. Previously published banded cases of leukemic infants under one year of age have been summarized. A review of the data in these 29 cases suggests that the appearance of a normal karyotype in acute leukemia of infants (less than or equal to 1 year old) is much less common than in other categories of acute leukemia. Fourteen out of 29 cases (48%) had chromosomal abnormalities involving 11q. Seven of eight ALL cases had aberrations with a breakpoint at 11q22-23; six cases had t(4;11), one case had a del(11q) and ins(19p), and another had a t(1;22;4). All of three AMMoL cases had translocations involving the long arm of #11. The percentage of patients with t(4;11) and certain translocations involving 11q in infants with ALL or AMMoL, respectively, is higher than that seen in ALL and AMMoL in general. Eleven out of 12 cases (92%) of infant acute leukemias with chromosomal abnormalities involving 11q22-23 were five months old or less.

Significance of a (4;11) translocation in acute lymphoblastic leukemia.

This report describes a case of null cell congenital acute lymphoblastic leukemia associated with a (4;11) translocation. This chromosome abnormality is associated with acute lymphoblastic leukemia and probably more specifically with congenital acute lymphoblastic leukemia. A review of the literature is presented.