Response to Tyrosine Kinase Inhibitors in Patients with BCR-ABL1 Positive Chronic Myeloid Leukemia; 13.5 Years’ Experience at Patan Hospital, Nepal

Background:Since the advent of Tyrosine Kinase Inhibitor (TKI), well controlled studies in developed world have shown that the life expectancy of patients with CML is comparable to normal people without the disease. But long-term follow up studies are lacking in resource poor setting. Methods:This is a retrospective follow up study looking at the molecular response and resistance to Tyrosine Kinase Inhibitors (TKI) in patients enrolled in the Max Access Program since February 2003 till March 2017. Patients with twoor more BCR-ABL1 levels by Karyotyping/ fluorescent in situ hybridization (FISH) / reverse transcriptase polymerase chain reaction (RT-PCR) were included. At baseline, complete blood count (CBC), renal function test (RFT), and liver function test (LFT) were evaluated. Bone marrow aspiration and biopsy for morphology, cytogenetic analysis by Karyotyping/FISH and/or molecular analysis by RT-PCR were also done if these tests were not performed earlier. FISH or RT-PCR was done on peripheral blood every 3–12 months as necessary if the patient could afford. Patients with warning response/failure underwent BCR-ABL1 Resistance Mutation Analysis (IRMA).Results:Three hundred and forty six (346) patients had two or more BCR-ABL1 monitoring tests done. Optimal response was seen in 49.42%. Similarly, suboptimal response and failure were seen in 16.5% and 34% respectively. Overall Survival is 89.6% (at 1.8 -165 months, mean 62 months) . If only CML related events is considered survival is 95.9%. Seventy seven (77) patients with a total of 80 BCR-ABL1 domain Imatinib Resistance Mutation Analyses (IRMA) showed 19 different types of mutations with the most common being T315I mutation (8 and 19.5%). About 22.25% of the total patients showed resistance to Glivec out of which 10.98% showed mutations. Nine patients underwent trial for treatment free response (TFR) and 5 of them relapsed between 2-8 months.Conclusions:Despite all the odds of having financial problem, accessibility problem due to distances, transportation, etc. and difficulty monitoring with routine BCR-ABL1 and IRMA, our findings show that the outcome of TKI therapy in our CML patients is comparable to well controlled studies done elsewhere. Overall survival, molecular and cytogenetic responses and mutations in our patients who developed resistance as well as TFR are also similar to other studies. The resistance rate of 22.25% is slightly higher compared to other studies in developed world. This is mainly because of poor monitoring due to unavailability of the test including IRMA in our country and affordability until 2012. It proves that TKI is very effective in CML even in a resource-poor, developing country

Relapsing polychondritis: a rare disease of multisystem involvement.

Relapsing Polychondritis (RP) is a rare connective tissue disease of unclear pathogenesis and may present with multisystem involvement. In this report we describe a case of Relapsing Polychondritis, a rare autoimmune disease of varied presentation, course, and response to therapy.

Hemidiaphragmatic paralysis: a rare complication of cervical herpes zoster.

Herpes zoster, a sequel of the reactivation of the varicella zoster virus, usually presents with cutaneous eruptions associated with intense pain and burning sensation in the affected dermatomes. Motor weakness, however, can sometimes complicate herpes zoster. In this report we present a case that had diaphragmatic motor weakness as a sequel of herpes zoster lesions in the neck.

Comparison of the clock test and a questionnaire - based test for screening for cognitive impairment in Nigerians

Background: Since it is projected that by 2020 seventy percent of the elderly will reside in developing countries; a reliable screening method for dementia and cognitive impairment in general in populations with diverse languages; culture; education and literacy will be needed. We sought to determine if the Clock Test; a screening test for dementia; was suitable for use in a Nigerian population. Study design: Cross-sectional survey of 54 men and 12 women from Northern Nigeria. Researchers administered two dementia screening tools: a questionnaire-based test adapted for use in a Nigerian population and the Clock Test. Results: Overall; 53.0of the subjects had an abnormal Clock Test whereas 10.6of the subjects had an abnormal questionnaire score. Only 9.1of the subjects had abnormal scores on both tests. Subjects with more schooling had a greater probability of having a positive clock concept (understanding that a circle represented a clock). Of those with more than 6 years of schooling; 91.0had a positive clock concept. Subjects with a negative clock concept were more likely to have an abnormal Clock Test (93.3) than a questionnaire (26.6). Conclusions: The main finding of our study was the discrepancy between the results of the Clock Test and the questionnaire. Performance on the Clock Test appeared to have been heavily influenced by education level; indicating the test is not universally applicable across cultures. The questionnaire-based test appears to reduce the effects of illiteracy on assessing dementia in a Nigerian population. Larger studies should be done to control for how education affects the assessment of dementia

Paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disorder of acquired origin and is clinically manifested by chronic hemolysis, thromboses in various sites, and bone marrow failure. The disease is so rare that the delay in the diagnosis is not uncommon and this bears a tremendous impact on patient management. We present this case to draw attention to this uncommon cause of hemolytic anemia, which should be considered in any patient, of any age, who has signs of chronic hemolysis.

Doenca de Wolman (xantomatose familiar).Relato de um caso. / Wolman's disease (familial xanthomatosis). Report of a case

Os autores apresentam um caso da doenca de Wolman, tambem conhecida como xantomatose familiar ou lipidose familiar de Wolman, caracterizada pela deposicao de esteres de colesterol no SRE e calcificacao bilateral das adrenais. A doenca apresenta-se precocemente na vida e evolui com progressiva hepatoesplenomegalia e ma absorcao intestinal. O prognostico e fatal