A Prospective Study on the Incidence and Outcomes of Neonatal Thrombocytopenia at a Tertiary Care Facility in Central Saudi Arabia.

BACKGROUND: The incidence of neonatal thrombocytopenia is low, yet highly dependent on the populations studied. PURPOSE: To assess the incidence of neonatal thrombocytopenia and identify factors associated with its outcomes, namely time to disease onset, recovery duration, and platelet count. METHODS: A prospective observational study was conducted between May and October 2013 at a large tertiary care facility in Saudi Arabia. Neonates with a platelet count of fewer than 150,000/µL of blood were followed up until their recovery or death. RESULTS: The period incidence of neonatal thrombocytopenia was 84/4379 (1.9%). The mortality rate associated with the condition was 68/100,000 births. The male-female ratio of neonates with thrombocytopenia was 2.4:1. The mean (standard deviation) time to disease onset was 1.83 (1.29) days, whereas that of recovery duration was 15.35 (18.46) days. The mean (standard deviation) platelet count at onset was 109,543 (32,826)/µL of blood, whereas that of the increase in platelet count from onset to recovery was 121,876 (78,218)/µL of blood. Treatment comprised monitoring/spontaneous recovery (n = 52, 64.2%) or platelet transfusion (n = 9, 11.1%), immunoglobulins (n = 8, 9.9%), or a combination of both (n = 12, 14.8%). Neonates with a higher gestational age (ß = 8061, t = 2.456) and late disease onset (ß = 26,178, t = 3.969) were more likely to have a larger increase in platelet count from onset to recovery than those with a lower gestational age (adjusted P = .017) and earlier disease onset (adjusted P < .001). IMPLICATIONS: The high incidence of neonatal thrombocytopenia in this Middle Eastern setting indicates that it may be dependent on the population studied. Special attention should be focused on neonates of lower gestational ages and with an early disease onset, because their platelet count recovery may be slower than that of the countergroup.

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

BCR-ABL kinase domain (KD) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-KD mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-KD. Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-KD mutation screening in late chronic phase CML patients for improved clinical management of disease.

Low Frequency of ETV6-RUNX1 (t 12; 21) in Saudi Arabian Pediatric Acute Lymphoblastic Leukemia Patients: Association with Clinical Parameters and Early Remission.

BACKGROUND: Pediatric acute lymphoblastic leukemia (pALL) patients at King Abdulaziz Medical City represent a pure Saudi Arabian population. ETV6-RUNX1 positive pALL patients have good prognosis as compared to ETV6-RUNX1 negative counterparts. Therefore, frequencies of these two patient groups have a huge consideration in treatment strategies of pALL in a given population. Different geographical locations have been reported to have different frequencies of ETV6-RUNX1 ranging from 10% in Southeast Asia to 30% in Australia. AIM: Therefore, the objective of this study was to establish the ETV6-RUNX1 status of Saudi Arabian pALL patients and its association with clinical parameters and early remission. MATERIALS AND METHODS: Clinical parameters and ETV6-RUNX1 status (using FISH technique) of pALL patients attending the Pediatric Oncology Clinic, King Abdulaziz Medical City, Riyadh from 2006 to 2011 were studied. Comparisons between ETV6-RUNX1 positive and negative groups were accomplished using chi-square test or Fisher's exact test. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Inc., Cary, NC). RESULTS: Out of 54 patients, 33 were male and 21 were females (ratio 1.57:1). B- and T-cell lineages were found in 47 (87%) and 7 (13%) patients respectively. Only 5 (9.3%) patients were ETV6-RUNX1 positive while 49(80.7%) were ETV6-RUNX1 negative. All ETV6-RUNX1 patients (100%) were of B-cell lineage and 80% (4/5) were in the 3-7 year age group. None of the ETV6-RUNX11 patients had ≥ 5% blasts (no remission) at day 14 as compared with 9% in the ETV6-RUNX1 negative group (Figure 1). CONCLUSIONS: Frequency of ETV6-RUNX1 positive patients (less than 10%) in our pALL patients is much lower than reported for most European countries, North America, Australia and Japan while it is in accordance with ETV6-RUNX1 frequencies from Egypt (11.6%), Pakistan (10%), Spain (2%) and India (5-7%). This shows ethnic differences in genetics of pALL as well as higher frequencies of ETV6-RUNX1 positive pALL mostly in more industrialized countries, probably due to some industrial pollutants or westernized lifestyle.