Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion.

Acute lymphoblastic leukemia (ALL) with recurrent genetic lesions, affecting a series of kinase genes, is associated with unfavorable prognosis, however, it could benefit from treatment with tyrosine kinase inhibitors (TKI). NUP214::ABL1 fusion is detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL), and is very rare in B-ALL. We present a case of adolescent with B-ALL and a cryptic NUP214::ABL1 fusion which was initially missed during diagnostic screening and was detected by additional RNA sequencing. Treatment with specific ABL-inhibitor Imatinib was added later in therapy with a good effect. Initial treatment according to conventional chemotherapy was complicated by severe side effects. At the end of Consolidation, the patient was stratified to a high risk group with allogeneic hematopoietic stem cell transplantation because of insufficient response to therapy. At that time, targeted RNA sequencing detected NUP214::ABL1 gene fusion which was previously missed due to a small microduplication in the 9q34 chromosome region. Gene variant analysis revealed no TKI-resistant ABL1 mutations; therefore, treatment with Imatinib was added to target the NUP214::ABL1 fusion protein. A negative minimal residual disease was achieved, and treatment was downgraded to intermediate risk protocol. Combining routine genetic assays with next-generation sequencing methods could prevent from missing atypical gene alterations. Identification of rare targetable genetic subtypes is of importance in order to introduce targeted therapy as early as possible that may improve survival and reduce toxicity. Treatment with ABL1 inhibitor imatinib mesylate revealed as a highly effective targeted therapy against the leukemia driving protein kinase.

Assessment of Risk Factors for Iron Deficiency Anemia in Infants and Young Children: A Case-Control Study.

INTRODUCTION: Iron deficiency anemia (IDA) is common in children aged 0-35 months in Lithuania. Nevertheless, there are no studies investigating IDA in this age group. We aimed to identify the major risk factors for disease development focusing on medical history and dietary habits. METHODS: A prospective case-control study was conducted in a university hospital. The enrolled cohort was divided into three groups: IDA infants (IDA-In; n = 36, aged 3-11 months), IDA children (IDA-Ch; n = 23, aged 12-32 months), and healthy controls (HCs; n = 32, aged 6-34 months). RESULTS: There was a higher number of premature, low birth weight (LBW), and faster gaining weight infants in the IDA-In group. Their diet diversity was lower than IDA-Ch and HC. In contrast, the IDA-Ch group had no signs of impaired iron stores at birth or higher iron need for fast growth; their diet diversity was similar to that of HC, but meat was introduced later as compared with those in the IDA-In and HC groups. Consumption of cow's milk was rather low among all study participants, but consumption of sugar-added products was found to be a new emerging problem. Exclusive breastfeeding did not differ in duration and prevalence; the age for introduction of complementary foods was similar in all groups. CONCLUSIONS: Low compliance with World Health Organization (WHO) recommendations on breastfeeding and complementary feeding suggests an urgent need for nutritional counseling in early childhood, especially in premature, LBW, and fast gaining weight infants.

An assessment of iron overload in children treated for cancer and nonmalignant hematologic disorders.

UNLABELLED: Our goal was to assess the natural fate of iron overload (IO) following transfusions of packed red blood cells (PRBCs) in children treated for cancer and nonmalignant disorders according to the intensity level of their treatment. Sixty-six children were followed up from February 2010 to March 2013. The transfusion burden was compared between three treatment intensity groups assigned according to the Intensity of Treatment Rating Scale 3.0 (ITR-3). IO was assessed by serial measurements of serum ferritin (SF) (n= 66) and quantification of tissue iron by magnetic resonance imaging (MRI) (n=12). Of the children studied, 36 % (24/66) received moderately intensive treatment (level 2), 21 % (14/ 66) received very intensive treatment (level 3), and 42 % (28/ 66) received the most intensive treatment (level 4). The number of PRBC (p=0.016), the total transfused volume (p= 0.026), and transfused volume adjusted to body weight (p= 0.004) were significantly higher in the level 4 group. By the median follow-up time of 35.5 months (range 8­133), 21­ 29 % of patients (including level 2 and level 3 children) had SF >1,000 µg/l 1 year after cessation of transfusions. The slowest decrease of SF was observed in the level 4 group. Initial MRI examination demonstrated either mild or moderate IO in the liver and spleen. Repetitive MRI showed significant improvement in relaxation time between the initial and follow-up MRI performances in the liver (5.9 vs. 8.6 ms, p= 0.03) and the spleen (4.3 vs. 8.8 ms, p=0.03). CONCLUSION: IO diminished over time, but in the level 4 patients, it was detectable for years after cessation of transfusions.

Liposomal amphotericin B and surgery as successful therapy for pulmonary Lichtheimia corymbifera zygomycosis in a pediatric patient with acute promyelocytic leukemia on antifungal prophylaxis with posaconazole.

Pulmonary zygomycosis, also referred to as mucormycosis, is a fungal infection of lungs caused by fungi of the order Mucorales in the class of Zygomycetes. It is usually associated with high morbidity and mortality. Here, we report the case of a 14-year-old girl with pediatric acute promyelocytic leukemia (APL) on antifungal prophylaxis with posaconazole, who developed pulmonary Lichtheimia corymbifera (formerly Absidia corymbifera) zygomycosis. She was successfully treated by means of liposomal amphotericin B (L-AmB) and surgery. To our knowledge, this is the first published report on pediatric APL and pulmonary zygomycosis in the English language literature. At present, the patient is in complete remission of her APL and without any signs of recurrence of zygomycosis. This report suggests that efficient diagnostics, increased physician awareness, and reliance on adjunctive surgical therapy can result in a favorable outcome of pulmonary zygomycosis in immunocompromised children with hematological malignancies.