Chronic Myeloid Leukemia: Clinical and Laboratory Features At Presentation To a Referral Hospital In Southern Nigeria

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5174-5174 ◽  
Author(s):  
Kaladada I. Korubo ◽  
Hannah Emmanuel Omunakwe ◽  
Chijioke A. Nwauche

Abstract Background Chronic Myeloid Leukaemia (CML) is one of the commonly diagnosed leukaemias and has been extensively studied, making it the first malignancy to have a constant identified mutation present which is relevant for diagnosis. CML is also a model for targeted therapy in the treatment of cancer. Before the development of molecular techniques in diagnosis of CML, the clinical and laboratory parameters which included spleen size, total white blood cell (WBC) count, peripheral and bone marrow smears were essential in making a diagnosis of CML. In a developing country with less availability of molecular techniques of diagnosis, these parameters are still invaluable. Here we present an eight year retrospective study of patients who were diagnosed with CML in our center, which is a tertiary referral center in the Niger-Delta zone of Nigeria. Methods We carried out a retrospective study of all CML cases who presented to the department of hematology at the University of Port Harcourt Teaching Hospital, Nigeria, from the year July 2004 – June 2012. Data were extracted from patients' records and included age, sex, absence/presence & duration of symptoms, full blood count and presence of Philadelphia chromosome. Other investigations done were erythrocyte sedimentation rate, uric acid, renal and liver function tests. Diagnosis of CML was made based on clinical features, full blood count, bone marrow aspirate and karyotyping for Philadelphia chromosome where available. The data generated from the above information were analyzed with SPSS statistical package software with results expressed in statistical tables. Results A total of 105 haematological malignancies were seen between July 2004 and June 2012 of which 34 (32.4%) were CML. The mean age of presentation was 32.4 ± 16.2 years (range 19 - 75 years, median 36.5 years). There were 18 males and 16 females. The males had a lower mean age than the females (37.3 vs. 40.4 years) but this was not statistically significant (p=0.59), however the median age of males and females were the same (36 vs. 36.5 years). Males were only slightly more affected than females (male, female ratio 1.1 : 1). No patient was asymptomatic at presentation. The commonest presenting clinical features were splenomegaly (91.2%), anemia (61.8%), fever (50%) and weight loss (50%). One patient had undergone a splenectomy. Seven (20.6%) presented as incidental findings while being investigated for other reasons due to development of complications such as renal failure, hearing loss, priapism, and had a higher mean WBC of 535.7 X 109/L. All the patients presented with leucocytosis (mean 287 X 109/L, range 72-1343 X 109/L). There was no case of thrombocytopenia, but nine (26.5%) had thrombocytosis with a mean platelet count of 639.1 X 109/L. Nineteen (55.9%) had a raised ESR. Bone marrow aspirate findings of all patients typically showed increased cellularity and marked myeloid hyperplasia. Of the total 34 CML patients, 3(8.8%) presented in the accelerated phase and only 1(2.9%) in the blastic phase, majority presented in the chronic phase. Karyotyping for Philadelphia chromosome was done for 12(35.3%) and was positive in all cases. Conclusion CML represented about a third of the haematological cancers seen at our center. Our median age of presentation is lower than Caucasian values (32.4 vs ∼60 years) as reported by other African literature. The males presented at an earlier age than the women although this was not statistically significant. The clinical and laboratory parameters are comparable to international studies, though our patients had very high WBC count at presentation. We did not have any asymptomatic patient. This may be attributed to lack of awareness on the importance of routine medical checkup and evaluation in low resource countries. However, a larger multi-center study is required to corroborate these findings. Disclosures: No relevant conflicts of interest to declare.

2019 ◽  
Vol 12 (3) ◽  
pp. e227821
Author(s):  
Adele Beck ◽  
Hannah Hunter ◽  
Simon Jackson ◽  
David Sheridan

A 17-year-old man with no significant past medical history presented with a 2-week history of worsening jaundice, lethargy, anorexia and progressive right upper quadrant abdominal pain. There were no stigmata of chronic liver disease. Initial investigations were suggestive of cholangitis with large intrahepatic and extrahepatic bile duct strictures but otherwise normal hepatic and splenic appearances. A percutaneous transhepatic cholangiogram with the positioning of drains was performed to alleviate the obstructive jaundice. Within 2 weeks of the first presentation, full blood count revealed a significantly raised white blood count and a subsequent peripheral blood smear and bone marrow were consistent with a diagnosis of acute myeloid leukaemia. Chemotherapy was started after partial improvement of his obstructive jaundice. Complete morphological and cytogenetic remission was obtained 4 weeks after the first cycle of chemotherapy (half dose of daunorubicin and full dose of cytarabine, treated off trial) on control bone marrow. The patient remains in remission.


2021 ◽  
Vol 20 ◽  
pp. 153303382110414
Author(s):  
Feiyue Zhu ◽  
Yesong Fu ◽  
Xiaojuan He

Objective: This study was undertaken to investigate eukaryotic translation initiation factor 3 subunit B (EIF3B) expression and its clinical value for indicating disease progression and prognosis in adult Philadelphia chromosome negative acute lymphoblastic leukemia (Ph− ALL) patients. Methods: Totally, 76 adult Ph− ALL patients and 30 healthy donors (HDs) were included. Bone marrow (BM) samples before therapy (baseline), after 4-week therapy of Ph− ALL patients and the BM samples of HDs were collected. Then, EIF3B expression in BM was detected by reverse transcription quantitative polymerase chain reaction. Results: EIF3B expression was increased in Ph− ALL patients compared with HDs, which distinguished Ph− ALL patients from HDs (area under the curve [AUC]: 0.928; 95% confidence interval [CI]: 0.882−0.974) by receiver operating characteristic curve. Furthermore, higher baseline EIF3B expression was associated with elevated white blood cell and bone marrow blasts, while it was associated with lower complete remission (CR) within 4 weeks and less allogeneic hematopoietic stem cell transplant achievements in Ph− ALL patients. Additionally, higher baseline EIF3B expression was associated with decreased disease-free survival but not overall survival. However, it was associated with raised 1-year mortality and 3-year mortality in Ph− ALL patients. After 4-week therapy, EIF3B expression was reduced in total Ph− ALL patients. Notably, the reduction of EIF3B expression was more obvious in Ph− ALL patients who achieved CR within 4 weeks compared with Ph− ALL patients who did not achieve CR within 4 weeks. Conclusion: EIF3B overexpression is related to worsened clinical features, poor treatment response and survival in adult Ph− ALL patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Raunak Rao ◽  
Spoorthy Kulkarni ◽  
Ian B. Wilkinson

Background. Myeloproliferative neoplasms are a heterogeneous group of disorders resulting from the abnormal proliferation of one or more terminal myeloid cells—established complications include thrombosis and haemorrhagic events; however, there is limited evidence to suggest an association with arterial hypertension. Herein, we report two independent cases of severe hypertension in JAK2 mutation-positive myeloproliferative neoplasms. Case Presentations. Case 1: a 39-year-old male was referred to our specialist hypertension unit with high blood pressure (BP) (200/120 mmHg), erythromelalgia, and headaches. We recorded elevated serum creatinine levels (146 μM) and panmyelosis. Bone marrow biopsy confirmed JAK2-mutation-positive polycythaemia vera. Renal imaging revealed renal artery stenosis. Aspirin, long-acting nifedipine, interferon-alpha 2A, and renal artery angioplasty were employed in management. BP reached below target levels to an average of 119/88 mmHg. Renal parameters normalised gradually alongside BP. Case 2: a 45-year-old male presented with high BP (208/131 mmHg), acrocyanosis, (vasculitic) skin rashes, and nonhealing ulcers. Fundoscopy showed optic disc blurring in the left eye and full blood count revealed thrombocytosis. Bone marrow biopsy confirmed JAK2-mutation-positive essential thrombocytosis. No renal artery stenosis was found. Cardiac output was measured at 5 L/min using an inert gas rebreathing method, providing an estimated peripheral vascular resistance of 1840 dynes/s/cm5. BP was well-controlled (reaching 130/70 mmHg) with CCBs. Conclusions. These presentations highlight the utility of full blood count analysis in patients with severe hypertension. Hyperviscosity and constitutive JAK-STAT activation are amongst the proposed pathophysiology linking myeloproliferative neoplasms and hypertension. Further experimental and clinical research is necessary to identify and understand possible interactions between BP and myeloproliferative neoplasms.


2020 ◽  
pp. 5169-5171
Author(s):  
Chris Hatton

Haematology is the study of the composition, function, and diseases of the blood. The approach to a patient suspected of having a haematological disorder begins with taking a history (particularly noting fatigue, weight loss, fever, and history of bleeding) and performing a clinical examination (looking for signs of anaemia, infection, bleeding, and signs of cellular infiltration causing splenomegaly and/or lymphadenopathy). Key investigations include a full blood count, a blood film, and (in selected cases) examination of the bone marrow. Further diagnostic tests now routinely performed on blood and marrow samples include immunophenotyping and cytogenetic and molecular analysis. Mutational signatures may be diagnostically useful and potentially define treatment, keeping haematology in the vanguard of advances in modern medicine.


Author(s):  
L Budding ◽  
M Coetzee ◽  
G Joubert

Background: In order to ensure that patients receive individualised treatment following bone marrow biopsy, it is necessary for clinicians to provide complete clinical information on bone marrow request forms (BMRFs). An audit of BMRFs six years previously showed poor completion, especially with regard to filling in full blood count results, transfusion history, medication history, information about the clinical examination and HIV status. This lead the laboratory to design a new bone marrow specimen request form. We did a follow-up audit to see if the new form had helped to improve the completion rates. Methods: We compared 400 forms to the 357 that were audited in 2013. The following details were recorded: date and time of collection, patient demographics, requesting doctor’s details, clinical information, current medication, transfusion history and HIV status, and details of the procedure completed by technologists, registrars and pathologists. Results: The 2019 follow-up audit showed significant improvements in the completion of the transfusion history, as well as the clinical examination and HIV status. Registrars and pathologists signed off forms regularly. The completion of patient demographic details, and requesting doctors’ names and telephone numbers worsened. Discussion and conclusion: We recommend that the form be simplified so the requesting doctors only need to tick yes or no, in a tick-box format, if a full blood count has been done in the preceding 24 hours. There needs to be a dedicated space for the hospital and laboratory stickers. Only the name and telephone number of one doctor should be requested. This doctor should preferably be the most senior doctor involved with patient care. All referring laboratories and hospitals will be consulted before updating the form. Unfortunately, it seems that the only way to force the completion of request forms is to introduce an electronic order entry system that does not accept incomplete forms.


Author(s):  
Chris Bunch

This chapter addresses the interpretation of the full blood count, blood film, bone marrow examination, and related tests in the diagnosis of haematological disorders. Examination of a stained blood film, which should always be requested if a blood count abnormality cannot readily be explained by the clinical context, may give clues to the cause of the abnormality or prove diagnostic. Examination of the bone marrow is essential to the proper evaluation and diagnosis of many haematological disorders. The simplest form of marrow examination involves needle aspiration of marrow cells from the posterior iliac crest; smears are made and stained in the same way as a blood film. Bone marrow can also be biopsied for histological examination, at the same time as marrow aspiration.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 736-736
Author(s):  
Hyang-Min Byun ◽  
Shahrooz Eshaghian ◽  
Jia Yi Jiang ◽  
Si Ho Choi ◽  
Laleh Ramezani ◽  
...  

Abstract Aberrant promoter DNA methylation is found in many cancers and is associated with aberrant gene silencing. Some abnormal cancer related methylation changes have been associated with a number of clinical features including pathologic features, prognosis, and treatment response. However, other DNA methylation changes do not appear to have phenotypic consequences and may reflect a stochastic event or a downstream event of tumorogenesis. In order to obtain a better understanding of DNA methylation changes in cancer we chose to study three very homogenous cancers: CML, APL and GIST. CML is a leukemia characterized by the Philadelphia chromosome, t(9:22), and is very sensitive to imatinib mesylate. APL is another leukemia characterized by a specific chromosomal translocation, t(15:17), and a high response to all-trans-retinoic acid. Lastly, GIST is a sarcoma with a high frequency of c-kit mutations and sensitivity to imatinib mesylate. In this study, we used bisulfite PCR/Pyrosequencing to accurately quantitate the absolute amount of DNA methylation of 15 genes (MDR, ID4, PROX1, ER, Jun B, p73, p15, ABL1, THBS1, p16, RASSF1A, RUNX3, SOCS1, RARA, and PML). We analyzed the blood and bone marrow of 58 patients with CML (chronic phase n=32, accelerated phase n=11, blast crisis n=13), and 23 patients with APL. We also analyzed tumors from 9 GIST patients. We show clearly that DNA methylation changes are not random events, but related to the biology of the cancer. We have identified at least four specific types of aberrant DNA methylation. Cancer specific hypermethylation of genes related to clinical phenotype. ID4 and PROX1 were hypermethylated in APL and CML, but not GIST. Methylation of these genes in CML was strongly associated with the development of blast crisis (P=0.0005), and the methylation of these two genes was also associated with an increase in the percentage of bone marrow blasts in APL (p<0.0001). DNA methylation related to geographic changes that are related to recombinatorial translocation events. ABL hypermethylation was isolated to CML patients who have the bcr-abl translocation. In contrast, RARalpha hypermethylation was unique to APL patients, who have the PML-RARalpha translocation. General DNA methylation changes associated with malignant transformation. Hypermethylation of MDR, ER, p16 and p15 was found in all three types of cancer. Interestingly, RUNX3 was hypermethylated in normal tissue, but became hypomethylated in all three cancers studied. Genes that are resistant to hypermethylation (p73 and RASSF1A). In conclusion, ID4 and PROX1 hypermethylation is a marker of disease progression in leukemia such as blast crisis in CML and higher percentage of bone marrow blasts in APL. Methylation of ABL and RARalpha are specific to CML and APL, respectively, and is likely related to specific chromosomal translocations. There are genes that are subject to small increases or decreases in DNA methylation that do not correlate with any obvious biology or clinical features. Finally, there are genes that are clearly resistant to DNA methylation changes. Our study shows that DNA methylation changes are clearly non-random events, and suggests there are several mechanisms that drive DNA methylation changes.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4844-4844
Author(s):  
Anil V. Kamat ◽  
Raphael Ezekwesili ◽  
Yasser El-Miedany

Abstract Introduction-Tumour necrosis factor- alpha (TNF α) inhibitors such as infliximab & etanercept have various applications such as severe rheumatoid arthritis, seronegative spondyloarthritis, vasculitis, crohn’s disease & psoriasis. There have been few reports of haematological complications arising in patients treated with anti-TNF a therapies. There has been only one reported case of development of acute myeloid leukaemia after initiation of etanercept therapy. Case report-A 57year old gentleman with HLA B27 negative ankylosing spondylitis presented with chest infection. His full blood count showed Hb 5.9 g/l WBC 3.8 × 10^9/L Neutrophil count 2.7 × 10^9/L Lymphocyte count 0.7 × 10^9/L Platelet count 89 × 10^9/L & Reticulocyte count 21 × 10^9/L. Occasional myeloblasts were seen on the blood film. He had been on biological therapy for ankylosing spondylitis with infliximab 5mg/kg infusion on 8 weekly basis for 18 months which was stopped due to lack of efficacy. Subsequently he had been treated with etanercept 50 mg subcutaneous once weekly for the past 16 weeks prior to this presentation. His full blood count prior to initiation of infliximab & etanercept was Hb 11.6 g/l WBC 16 × 10^9/L Neutrophil count 12.8 × 10^9/L Lymphocyte count 2.1 × 10^9/L Platelet count 655 × 10^9/L and Hb 11.0 g/l WBC 8.2 × 10^9/L Neutrophil count 4.9 × 10^9/L Lymphocyte count 2.4 × 10^9/L Platelet count 591 × 10^9/L, respectively. He underwent bone marrow investigations. Bone marrow aspirate was aparticulate with dyshaemopoeisis. Dyserythropoeisis in form of irregular nuclei, occasional binucleated cells & delayed nucleo-cytoplasmic maturation was seen along with dysmyelopoeisis in form of binucleated cells & pelger forms. Blasts amounted to 14% of nucleated cells. Overall, impression was in keeping with refractory anemia with excess of blasts (RAEB-2). Trephine biopsy showed mildly hypocellular bone marrow with markedly disordered haemopoeisis. There was trilineage dysplasia with abundant micromegakaryocytes with immunocytochemistry for CD117 showing increased number of progenitors (10–20%). The appearances were in keeping with myelodysplasia with excess of CD117 positive progenitors. Cytogenetic study failed. The sepsis responded to broad spectrum antibiotics but he continues on red cell & platelet support on a weekly basis. Conclusion The chronology points to a TNF α inhibitor mediated effect in this patient. Despite the close temporal association between exposure to TNF α inhibitor therapy and the presentation of myelodysplasia in this patient, a causal relationship cannot be established with confidence. Tumour necrosis factor inhibitors find wide applications in inflammatory conditions with high TNF. Such treatment may be associated with uncommon complications. It is of interest to note there are ongoing trials using TNF α inhibitors in myelodysplastic syndrome. Checking a full blood count periodically, and immediately if the patient is unwell is recommended.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3291-3291
Author(s):  
Josep-Maria Ribera ◽  
Albert Oriol ◽  
Mireia Morgades ◽  
Josep Sarra ◽  
Pau Montesinos ◽  
...  

Abstract Background and aim: Current therapeutic protocols for adult ALL consider MRD together with the baseline risk factors (age, WBC count, immunophenotype, cytogenetics) and speed in response to therapy for treatment decisions. On the other hand, the systematic use of allogeneic SCT for all adult patients (pts) with Ph- HR-ALL is still a matter of debate. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels (assessed by cytofluorometry at the end of induction and consolidation therapy) in HR Ph- adult ALL patients. Patients and methods: HR ALL included one or more of the following baseline parameters: age 30–60 yr, WBC count >25x109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy (≥10% blasts in bone marrow assessed on d14) intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level >0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level <0.05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR. Results: On June 2008,192 patients were evaluable (mean (SD) age 37(10) yr, 105 males, 119 precursor B-ALL, 73 T-ALL, WBC count 65(99) x109/L). Induction death: 17(9%), resistance: 12 (6%), CR: 163 (85%). MRD<0.1% was observed in 64% of CR patients. Early consolidation was completed in 126 patients. MRD<0.05% was observed in 65% at the end of consolidation. On June 2008, allogeneic SCT was performed to 30 pts (15 from HLA-identical siblings and 15 MUD), TRM 11 pts, relapse 4, CCR 15. Delayed consolidation and maintenance was administered to 79 pts (toxic death 4 pts, relapse 21, CCR 54). Four-yr DFS for the whole series was 36±7% (37±19% for pts assigned to SCT and 56±12% for those assigned to chemotherapy). Slow cytologic response was associated with a lower CR probability and higher induction death. No baseline variable was associated with a higher probability of MRD negativity after induction or consolidation. Conclusions: These results suggest that in HR Ph- adult ALL pts with adequate response to induction and adequate clearance of MDR the results of therapy are not hampered by avoiding allogeneic SCT. Supported by grants P-EF/07 from FIJC and RD 06/0020/1014 from Instituto Carlos III


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