Congenital leukemia is a rare malignancy diagnosed in
the first month of life. One of the common associations with congenital
leukemia is Down syndrome. We report a rare trio of Down syndrome,
transient myeloid leukemia and a urological abnormality in the form of
pelviureteric junction obstruction.
Case Report
A one-month-old boy was referred to us with a
diagnosis of pelviureteric junction obstruction. The child was a full
term delivery; the maternal age was 28 years. The child had an elder
brother who was normal. The mother had a normal antenatal period and did
not receive any medications throughout pregnancy. The neonate had
features of Down syndrome (low set ears, protruded tongue, flattened
nasal bridge, mongoloid slant of eyes), and a left renal lump. There was
no hepatosplenomegaly, lymphadenopathy or any cutaneous lesions over the
body. All the other systems were normal.
Hematological investigations showed hemoglobin level
of 10 g/dL, a total leukocyte count of 40,200/ cumm and platelet count
of 40,000/cumm. The peripheral blood smear showed normocytic
normochromic red cells. There was marked leukocytosis with a shift to
the left, with 27% polymorphs, 23% lymphocytes, 41% blast cells, 7%
myelocytes and 2% metamyelocytes. The ratio of immature neutrophils to
total cells was normal (<0.2). The blood urea level was 35 mg/dL and
creatinine 0.8 mg/dL; electrolytes were within normal limits. CRP was
negative and the blood gas analysis was normal. The blood culture was
sterile. Bone marrow examination showed predominant marrow cells, more
than 85% of which were of granulocytic origin; 43% were blasts,
morphologically myelo-blasts. Myelocytes and polymorphs cons-tituted 25%
and 24% cells respectively. Occasional blast cells with Auer rod were
also noted. Cytochemistry was positive for Sudan Black and PAS was
negative. Erythropoiesis was markedly depleted and megakaryocytes were
scanty. The diagnosis of left pelvi-ureteric junction obstruction was
confirmed on ultrasound, intravenous pyelography and DTPA renal scan.
Chromosomal study showed 47 XY, +21 Karyotype. The lymphocyte culture
showed free trisomy 21 with normal sex chromosomes. There was no
evidence of fragility or translocation.
The child received antibiotic prophylaxis
(amoxicillin 5 mg/kg/day). Follow up was done for the kidney with serial
ultrasound examinations and DTPA scans every three-monthly. Serial
hematological monitoring was done monthly. During the repeat
hematological studies, the number of blast cells decreased and the
polymorphs and lymphocytes increased. At the age of 6 months, the
hematological investigations were normal with 1% blasts on peripheral
smear. Bone marrow examination showed less than 4% blast cells. The
child had pyelo-plasty for pelviureteric junction obstruction at the age
of nine months. The postoperative period was uneventful. The child was
well and on regular follow up nine months after the surgery. A repeat
hematological examination six months after the surgery was also normal.
Discussion
Leukemia in the newborn period has been associated
with Down syndrome(1,2), Turner syndrome(3), mosaic monosomy 7(4) and
trisomy 9(5). Studies have shown an estimated risk of leukemia 14-30
times in patients with Down syndrome(6).
Congenital leukemia is a rare malignancy diagnosed
before four weeks of age(7). The criteria, which must be fulfilled for
diagnosis are (i) proliferation of immature leukemia
cells; (ii) infiltration of these cells into non hemopoietic
tissue; (iii) absence of other disease processes such as
congenital hypoxia, erythroblastosis fetalis, congenital syphilis that
can cause a leukemoid or leukoerythro-blastic reaction, mimicking
congenital leukemia(8).
Newborn infants with Down syndrome frequently present
with a disorder character-ized by the appearance of primitive cells in
the peripheral blood. These cells have been characterized with a variety
of ancillary techniques as megakaryoblasts. Many different names have
been used to describe this disorder, the most common of which is
transient myeloproliferative disorder. Although the hematological
picture is indistinguishable from leukemia, it has been difficult to
accept this as a true leukemia because in most instances, the disease
disappears spontaneously. However, there is evidence that the disorder
is truly leukemia, and therefore it is referred to as transient
leukemia. In view of the myeloproliferative disorders or ineffective
regulation of granulopoesis resulting in this disease, it has also been
called transient abnormal myelopoesis(8).
In a study at the Hospital for Sick Children,
following conclusions were drawn: (i) Approximately 20% of
leukemia (excluding transient leukemia) in Down syndrome is acute
megakaryoblastic leukemia; (ii) Approximately 20% of all leukemia
in Down syndrome is transient leukemia; (iii) Transient leukemia
in Down syndrome is acute megakaryoblastic leukemia (M7); (iv)
Recurrence of acute megakaryo-blastic leukemia occurs in 20-25% of cases
of transient leukemia; (v) The incidence of acute
megakaryoblastic leukemia in Down syndrome is estimated to be 400 times
that in normal children(9).
The basis of this association has been hypothesized
to be influenced by the mechanism of the extra chromosome(6). Serial
cytogenetic studies using banding techniques at various stages during
the course of the disease (preleukemia, leukemia, remission and relapse)
showed several chromosomal abnormalities (unbalanced translocation
between chromosomes 1 and 4 leading to trisomy 1q, trisomy 7q, monosomy
7p, and a reciprocal translocation between chromosomes 10 and 16(10).
Sometimes in Down syndrome one cannot clinicaly and
hematologically differentiate between acute leukemia and transient
myelo-proliferative disorder. Judicious supportive care and clinical
monitoring for 3-6 weeks is necessary. If clinical or hematological
deterioration continues, the possibility of transient myeloproliferative
disorder is ruled out and appropriate chemotherapy should be
instituted(3,8).
No evidence of hepatosplenomegaly was noted in our
patient. Cutaneous manifesta-tions which contain infiltrates of leukemic
cells were also absent. Serial hematological investigations showed a
gradual decline in the number of blasts, which reduced to almost 25% by
the end of the third month.
Transient leukemia is not associated with any
abnormal signs or symptoms. Our patient however, had an associated
pelviureteric junction obstruction, the association of which is very
rare, both with Down syndrome and transient myeloid leukemia.
Malformations like ventricular septal defect, duodenal atresia, cleft
lip and palate are known to be commonly associated with Down
syndrome(11). The only urological anomaly consistently related to this
disease is posterior urethral valves(12,13). Extensive review of
literature does not show any reports of the presence of this rare trio
of Down syndrome, urogenital and transient myeloid leukemia. The
long-term prognosis of transient leukemia is good. In majority of the
cases, the disease disappears and there are no recurrences or long-term
side effects. However, acute mekaryoblastic leukemia may develop within
the first 4 years of life, and this makes a regular follow up mandatory.
