Latest Research News on Lymphocytic Leukaemia : Nov 2020

Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia is the commonest form of leukaemia in Europe and North America, and mainly, though not exclusively, affects older individuals. It has a very variable course, with survival ranging from months to decades. Major progress has been made in identification of molecular and cellular markers that could predict disease progression in patients with chronic lymphocytic leukaemia. In particular, the mutational profile of immunoglobulin genes and some cytogenetic abnormalities are important predictors of prognosis. However, these advances have raised new questions about the biology, prognosis, and management of chronic lymphocytic leukaemia, some of which are addressed here. In particular, we discuss how better understanding of the function of the B-cell receptor, the nature of genetic lesions, and the balance between proliferation and apoptosis have affected our ability to assess prognosis and to manage chronic lymphocytic leukaemia. Available treatments generally induce remission, although nearly all patients relapse, and chronic lymphocytic leukaemia remains an incurable disease. Advances in molecular biology have enhanced our understanding of the pathophysiology of the disease and, together with development of new therapeutic agents, have made management of chronic lymphocytic leukaemia more rational and more effective than previously. Unfortunately, we know of no way that chronic lymphocytic leukaemia can be prevented. Early detection is practised widely, but seemingly makes no difference to the patient’s eventual outcome. [1]


Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. [2]

Lymphocyte doubling time in chronic lymphocytic leukaemia: analysis of its prognostic significance

In 100 untreated patients with chronic lymphocytic leukaemia (CLL) lymphocyte doubling time (LDT) has been investigated in relationship with clinical stages, bone marrow histological patterns, treatment‐free period and survival. Although partially correlated with clinical stages and bone marrow patterns. LDT has a clear prognostic significance by itself: whereas a LDT of 12 or less months identifies a population of patients with poor prognosis, a LDT higher than 12 months is indicative of good prognosis as substantiated by a long treatment‐free period and survival. This simple parameter can be useful in the clinical management of CLL patients. [3]

Clinical and Haematological Pattern of Chronic Lymphocytic Leukaemia in Sudanese Patients

Aims: Chronic lymphocytic leukemia is the most frequent adult leukemia in Western countries accounting for 25 to 30% of all leukemic patients. The clinical and haematological features vary from patient to patient. The aim of this study is to describe the clinical presentation of chronic lymphocytic leukemia, to evaluate haematological patterns of the disease in the peripheral blood and bone marrow and to correlate them with the clinical stage of the disease.

Study Design: This is a retrospective descriptive study.

Place and Duration: Radio Isotope Centre Khartoum (RICK), haematology laboratory during the period of January 2010 to December 2011.

Methodology: The data were collected at the haematology laboratory from patients’ records as well as from a special questionnaire designed for this study. Clinical data, complete blood count, bone marrow examination and immunophenotyping results were used.

Results: Out of 98 cases studied 69 (70.4%) were males and 29 (29.6%) were females. Sixteen patients (16.3%) were less than 50 years old (young patients) and 82 (83.7%) were more than 50 years of age (elderly patients). 49.1% of the patients were from western Sudan. Eight patients (8.2%) were asymptomatic. Absolute lymphocyte count above 5× 109/L had significant association with diffuse pattern of infiltration (P value=0.035) and was not significantly associated with advanced Rai stage (stage III 32.6%, Rai stage IV 22.8%) (P value=0.710).

Conclusion: Clinical and haematological pattern of chronic lymphocytic leukaemia in Sudanese patients has comparable results with previous studies in other parts of the world. Most of the patients were elderly male, from western Sudan presented with nonspecific symptoms, generalized lymphadenopathy and leukocytosis. The majority of patients presented in advanced stage at the diagnosis. [4]

Acute Lymphoblastic Leukaemia in Pregnancy: A Case Report

Background: Acute Lymphoblastic leukaemia (ALL) is a malignant disorder which originates in a single B–or T-lymphocytes progenitor as a result of somatic mutation. ALL represents about 15% of all malignancies in 1-15 year olds, 5% in 15-19 year olds, and <10% of malignancy in >20 year olds. This condition is rare in pregnancy and when it occurs, its management and the use of chemotherapy during pregnancy, poses a significant risk to both the mother and fetus.

Aim: To underscore the difficult dilemma physicians are faced with in the management of ALL in pregnancy.

Study Design: Case study.

Place of Study: Obstetrics & Gynaecology Department of the Federal Medical Centre, Bida, Nigeria.

Methods: A review of the index case was conducted at the Obstetrics & Gynaecology Department of the Federal Medical Centre, Bida-a tertiary health care facility in Nigeria. This review took into cognizance the patient’s demographic bio-data, case history, methods of diagnosis and various supportive measures.

A comprehensive analysis and account of events during this period were also reviewed.

Results: This case identifies a 26-year old gravida 2, para 1+0, a full term housewife and secondary school leaver, a Muslim background from a tribe of the Nupe part of Niger State. She was on a routine antenatal visit to Obstetrics Unit, when patient was noticed to have purpuric lesions. She was subsequently referred to our unit (Haematology Department) at a gestational age of 22 weeks 4 days along with florid features of bleeding diathesis. A complete blood count, cytochemical, Immunophenotyping and molecular analysis done classified patient as having a Ph Negative, pre B acute lymphoblastic leukaemia in pregnancy. Patient was then offered some supportive measures though inadequate due to the absence of aphaeretic machine in the centre. Patient had early uneventful spontaneous vaginal delivery of a live baby (birth weight; 2.6kg) at 30 weeks gestation thereby making administration of chemotherapy much less worrisome. Meanwhile, mother and baby remain clinically stable while being followed up on the aftermath of remission induction of combination chemotherapy.

Conclusion: Supportive management for ALL patients with anaemia and thrombocytopaenia is a necessary pre-induction workup step, and as in this case, would allow room for fetal growth and lung maturity; when the fetus would be mature enough to cope with extra-uterine life but also without endangering the health of the mother. This patient however, had early spontaneous vaginal delivery precluding the anticipated risk of fetal exposure to cytotoxic agents. [5]

 

Reference

[1] Dighiero, G. and Hamblin, T.J., 2008. Chronic lymphocytic leukaemia. The Lancet, 371(9617), pp.1017-1029.

[2] Puente, X.S., Pinyol, M., Quesada, V., Conde, L., Ordóñez, G.R., Villamor, N., Escaramis, G., Jares, P., Beà, S., González-Díaz, M. and Bassaganyas, L., 2011. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature, 475(7354), pp.101-105.

[3] Montserrat, E., Sanchez‐Bisono, J., Viñolas, N. and Rozman, C., 1986. Lymphocyte doubling time in chronic lymphocytic leukaemia: analysis of its prognostic significance. British journal of haematology, 62(3), pp.567-575.

[4] Abd Elgleel Mohammed Ahmed, R. and Mohammed Osman, I. (2017) “Clinical and Haematological Pattern of Chronic Lymphocytic Leukaemia in Sudanese Patients”, International Blood Research & Reviews, 7(1), pp. 1-10. doi: 10.9734/IBRR/2017/31359.

[5] Amiwero, C. E., Izuegbuna, O. O. and Olowosulu, R. .O. (2014) “Acute Lymphoblastic Leukaemia in Pregnancy: A Case Report”, Journal of Advances in Medicine and Medical Research, 4(21), pp. 3924-3932. doi: 10.9734/BJMMR/2014/9531.

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