Discussion
Because of genetic features and clinical characteristics infant leukemias are different from other childhood leukemias. Median duration of event free survival is 11 months(4). It is well known that hyperleukocytosis and MLL rearrangement in infant leukemia are associated with poor prognosis (1). Unlike these features of infant leukemias this patient didn’t presented with hyperleukoctosis and she hadn’t MLL rearrangement. In this case who had a good prednisolone response, t (5; 15) (p15;q11.2) was detected in cytogenetic analysis.
t(5; 15) was first reported in three infant ALL in 1987 (4,8). Seven infant ALL and only two childhood ALL patients with t (5; 15) (p15; q11-13) was reported until 2014 (6,9,10). On the basis of these data it was speculated that this chromosomal abnormality was characteristics of infant ALL and related with good prognosis(6).
Although CD10 weak positivity (6) is noteworthy in cases with t(5; 15) complete remission was achieved with induction therapy. Also event free survival of cases with t (5; 15) was better than those with MLL rearrangement (9). On the other hand 45-month-old girl reported by Kwon et al. had a good prednisolon response and achieved complete remission with induction therapy (10).
The 21-month-old boy reported by Lee et al. achieved remission 3 months after start of chemotherapy. However, Lee et al. reported that t (5; 15) was detected in cytogenetic analysis during relapse and they stated that it would be find positive at diagnosis if cytogenetic analysis was performed (9). If it can be detected before morphological relapse, it will be useful for the follow-up of patients. However infant leukemias with t(5; 15) and their clinical outcomes need to be reported.
On the other hand while hyperleukocytosis was detected in two of the cases, other two cases were not known. The remaining patients with t(5; 15) did not have hyperleukocytosis reported so far (6,9,10), like our patient. Extramedullary infiltration was reported only one of these patients. We thought that renal enlargement was related with extramedullary infiltration because her kidney shrunk in normal size with induction therapy.
Translocations such as t(9:22), t(1; 19), t(12; 21) known to be associated with leukemias and can be detected using RT-PCR and FISH. But cytogentic analysis still significant at the time of leukemia diagnosis. If we didn’t perform cytogenetic analysis on bone marrow sample at diagnosis we couldn’t catch t(5;15) in this case. On the other hand cytogenetic analysis not always available. For instance Heerema and et al who reported first three infant ALL cases with t(5;15) could obtain 39 cytogenetic analyses of 100 infant ALL in their study (4).
In addition, our patient had an ectrodactyly on her right hand (Figure 1). Split-hand / split-foot malformation (SHFM) defined ectrodactyly is seen once in 90,000 live births. Although it shows autosomal dominant inheritance autosomal recessive inheritenace has been reported. It is generally sporadic but it may be familial. There are syndactyly and aplasia in the phalanges with midline cleft in hand. There was no ectrodactyly in our patient’s family member. SHFM is a heterogeneous condition caused by genetic abnormalities. Thus classified according to genetic defect and association with cleft palate-lip anomaly, hearing loss and fallot tetralogy (12-14). Our patient had ’isolated’ ectrodactyly. Besides, ALL cases with t(5; 15) with ectrodactyly have not been reported yet.
Among the childhood malignancies, congenital anomalies are most common in leukemias. These anomalies include cleft palate, spina bifida, rib anomalies and birthmarks(15). It is suggested that rib anomalies may be associated with childhood leukemias (16). However the relationship between a specific congenital anomaly and leukemias is not known except Down Syndrome. Those with congenital anomalies were reported to have more cancer diagnoses in infancy than those without(17).
In conclusion, the case of infant leukemia reported here is the first case who had ectrodactyly with t (5:15). We consider that the clinical features, response to treatment and concomitant congenital anomaly of this case contribute to knowledge about infant leukemias.
Authors have no conflict of interest to declare.
ETHICS STATEMENT: Parents of patient have permitted with signature to publish their children’s photos.