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Systematic review of pre-clinical chronic myeloid leukaemia

Kuan JW, Su AT, Leong CF, Osato M, Sashida G

Int J Hematol, 2018 Nov;108(5):465-484.
PMID: 30218276 DOI: 10.1007/s12185-018-2528-x

BACKGROUND: Studies of a provisional entity pre-clinical chronic myeloid leukaemia (CML), which precedes chronic phase (CP) without leucocytosis or blood/marrow feature of CML CP, has been increasing.
OBJECTIVE: To perform a systematic review of pre-clinical CML and analysis the data relevant to disease progression to CML CP.
METHOD: We performed a literature search on 16 July 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data and evaluated the quality of studies using an 8-item tool, independently. The outcomes were percentage of Philadelphia chromosome in the number of metaphases examined (Ph%), correlation between Ph% and blood count and time progress to CML.
RESULT: Our initial search returned 4770 studies. A total of 10 studies with a total 17 subjects were included. The lowest Ph%, which eventually progresses to CML, was 10%. Absolute basophil count seemed to correlate better with Ph% compared to total white cell and absolute eosinophil count. The time from the first documented pre-clinical CML to CML ranged from 12 to 48 months. The overall quality of the included studies was average.
CONCLUSION: This is the first systematic review on pre-clinical CML. This entity requires additional large-scale studies.
Fulltext A Preliminary Study on Coagulation Parameters and Sterility of Thawed Refrozen Fresh Frozen Plasma

Draman R, Yousuf R, Abdul Aziz S, Ding CH, Zainol S, Leong CF

Indian J Hematol Blood Transfus, 2020 Jan;36(1):112-116.
PMID: 32174694 DOI: 10.1007/s12288-019-01171-0

Thawed fresh frozen plasma (FFP) if not used within 6 h, may have to be discarded due to the risk of contamination and uncertainty about its quality. The main objective of this study was to evaluate the levels of coagulation Factor II (FII), Factor VIII (FVIII), fibrinogen and bacterial growth in thawed refrozen FFP. Thirty FFP samples were collected from healthy donors. FFP were thawed in water bath at 37 °C for 20-25 min. Approximately 10 mL of plasma from each FFP unit was tested for FII, FVIII, fibrinogen and sterility. The thawed FFP units were then kept at 4 °C for 6 h before being refrozen and stored at - 20 °C. Two weeks later, the refrozen FFP were thawed again and representative samples were analysed as before. There was a significant decline in the mean FVIII level, from 155.77% to 85.6% at second thaw. The mean FII level increased significantly from 74.9% to 82%, whereas the mean fibrinogen level fell from 3.34g/L to 3.28 g/L, but the decline was not statistically significant. There was no bacterial contamination in all samples at both time points. Refrozen plasma may be considered as an alternative to the storage of thawed unused FFP provided they are kept in a controlled environment to reduce wastage. These thawed refrozen FFP can be used later in bleeding cases like other FFP as the levels of FVIII are still within the standard haematology range (0.5-2 IU/mL) and above the minimal level of 30% coagulation factors required for adequate haemostasis.
Fulltext Double Philadelphia chromosome-positive B acute lymphoblastic leukaemia in an elderly patient

Tang YL, Raja Sabudin RZ, Leong CF, Ko CC, Chia WK, Salwati S, et al.

Malays J Pathol, 2015 Dec;37(3):275-9.
PMID: 26712675 MyJurnal

A rare case of double Philadelphia chromosome-positive B Acute lymphoblastic Leukaemia (B-ALL) is reported here. A 60-year-old lady presented with one month history of fever, submandibular lymphadenopathy, loss of appetite and weight loss. Physical examination revealed multiple palpable cervical lymph nodes. Blood film showed leucocytosis with 72% blasts. Bone marrow assessment confirmed a diagnosis of B-ALL with presence of double Philadelphia (Ph) chromosomes. As she was very ill, she was initially treated with an attenuated regimen of induction chemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) along with intrathecal chemotherapy comprising methotrexate, cytarabine and hydrocortisone. Bone marrow examination post-induction chemotherapy showed >5% blasts. She was subsequently re-induced with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) along with intrathecal chemotherapy, following which she went into complete remission. Consolidation chemotherapy consisting of methotrexate, methylprednisolone, cytarabine, intrathecal chemotherapy and imatinib was subsequently administered followed by maintenance chemotherapy consisting of vincristine, prednisolone and imatinib (IDEAMOP). She developed spontaneous bruises and relapsed four months into her maintenance chemotherapy with 90% blasts in the bone marrow which was treated with fludarabine, cytarabine and granulocyte colony stimulating factor (FLAG). Unfortunately she developed neutropenic sepsis which was complicated by invasive lung aspergillosis. Bone marrow examination post-FLAG showed 80% blasts. Despite aggressive antifungal therapy, her lung infection worsened and she finally succumbed to her illness 13 months after the initial diagnosis. We highlight a rare case of elderly B-ALL with double Ph chromosomes which carries a poor prognosis despite aggressive treatment for the disease and its complications.
Predictors of the yield of mobilized peripheral blood CD34+ cells in HLA-matched sibling donor

Fadilah SA, Mohd-Razif MI, Seery ZA, Nor-Rafeah T, Wan-Fariza WJ, Habsah A, et al.

Transfus Apher Sci, 2013 Dec;49(3):583-9.
PMID: 24012241 DOI: 10.1016/j.transci.2013.07.032

We examined the donor factors that may affect the yield of peripheral blood stem cell (PBSC) mobilized from healthy donors. Pre-apheresis PB-CD34(+) cell count was the only factor that correlated with PBSC yield. Leukocyte count (LC) and monocyte count (MC) correlated with PB-CD34(+) cell. Male gender and PB-CD34(+) cell count of at least 87.1/μL and 69.8/μL on day-4 and -5 of G-CSF were associated with the ability to harvest at least 5×10(6)/kg CD34(+) cells after one apheresis. We concluded that gender and PB-CD34(+) cell count are important predictors of PBSC yield. LC and MC may serve as surrogate markers for estimating the PB-CD34(+) cell count.
Clinical usefulness of tumour markers

Lai LC, Cheong SK, Goh KL, Leong CF, Loh CS, Lopez JB, et al.

Malays J Pathol, 2003 Dec;25(2):83-105.
PMID: 16196365

Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.
Importance of extended blood group genotyping in multiply transfused patients

Osman NH, Sathar J, Leong CF, Zulkifli NF, Raja Sabudin RZA, Othman A, et al.

Transfus Apher Sci, 2017 Jun;56(3):410-416.
PMID: 28438419 DOI: 10.1016/j.transci.2017.03.009

Blood group antigen systems are not limited to the ABO blood groups. There is increasing interest in the detection of extended blood group systems on the red cell surface. The conventional method used to determine extended blood group antigens or red cell phenotype is by serological testing, which is based on the detection of visible haemagglutination or the presence of haemolysis. However, this technique has many limitations due to recent exposure to donor red cell, certain drugs or medications or other diseases that may alter the red cell membrane. We aimed to determine the red cell blood group genotype by SNP real time PCR and to compare the results with the conventional serological methods in multiply transfused patients. Sixty-three patients participated in this study whose peripheral blood was collected and blood group phenotype was determined by serological tube method while the genotype was performed using TaqMan®Single Nucleotide Polymorphism (SNP) RT-PCR assays for RHEe, RHCc, Kidd and Duffy blood group systems. Discrepancies were found between the phenotype and genotype results for all blood groups tested. Accurate red blood cell antigen profiling is important for patients requiring multiple transfusions. The SNP RT-PCR platform is a reliable alternative to the conventional method.
Marrow talaromycosis as the initial presentation in a case of Burkitt lymphoma

Hasbullah NE, Raja Sabudin RZA, Asri AS, Yusof N, Leong CF, Mohammed F, et al.

Malays J Pathol, 2024 Aug;46(2):325-329.
PMID: 39207011

Talaromyces marneffei is a thermally dimorphic fungus which causes opportunistic infections in immunocompromised individuals. The diagnosis of T. marneffei infection rests on the microscopic demonstration of the fungus in the tissues and/or isolation of the fungus from clinical specimens. In this report, we discuss a case involving a 23-year-old man who presented with a history of intermittent fever, cough and constitutional symptoms. Clinically, the patient exhibited pallor, jaundice, generalized seborrhoeic dermatitis, hepatomegaly, and small palpable cervical lymph nodes. A computed tomography (CT) scan of the abdomen showed homogenous hypodense lesions in both liver lobes. HIV screening result was reactive. Microscopic examination of the bone marrow aspirate smear and trephine biopsy identified fungal bodies, and culture of the marrow aspirate confirmed the presence of T. marneffei. Notably, the liver biopsy revealed Burkitt lymphoma alongside fungal bodies. He was treated with intravenous Amphotericin B but ultimately succumbed to the illness due to severe metabolic acidosis and multiorgan failure. This case underscores the importance of presumptive diagnosis through morphological or histological examination of bone marrow samples, as microbiologic culture methods can be time-consuming. Timely diagnosis and aggressive treatment are critical in managing patients with T. marneffei infection.
Early relapse after complete remission of primary plasma cell leukaemia manifesting clonal evolution: A case report

Nyunt WWT, Abdul Jalil D, Zakariah NA, Abdul Karim N, Mohd Idris MR, Nasuruddin DN, et al.

Malays J Pathol, 2020 Apr;42(1):143-150.
PMID: 32342945

INTRODUCTION: Plasma cell leukaemia (PCL) is a rare variant of multiple myeloma. We report a case of PCL to demonstrate the clonal evolution, resulting in disease relapse after achieving complete remission, and its aggressive nature of the disease, leading to poor clinical outcome.
CASE REPORT: A 69-year-old man presented with a three-day-history of worsening generalized body weakness, poor oral intake, nausea, significant loss of weight and lower back pain. He was diagnosed as primary PCL, based on hypercalcaemia, renal insufficiency, anaemia, thrombocytopenia, lytic bone lesions, 24% abnormal plasma cells in peripheral blood, immunophenotype of clonal plasma cells which were positive for CD38, CD138 and CD56 markers with kappa light chain restriction, 49% abnormal plasma cells in bone marrow, monoclonal paraprotein (IgG kappa) in serum and urine, and positive IGH rearrangement (Fluorescence in-situ hybridisation, FISH). He achieved complete remission after four cycles of Bortezomib-based therapy. There was a plan for high-dose therapy plus autologous haematopoietic cell transplantation. A month later, the disease relapsed, as evidenced by 94% abnormal plasma cells in his bone marrow aspirate, complex karyotype and abnormal FISH results. He passed away a few days later, from severe septicaemia. Time-to-progression of disease was 1 month and overall survival was 5 months.
DISCUSSION: This case report illustrates the clonal evolution and aggressive nature of primary PCL with older age at presentation, leading to a shorter duration of remission and overall survival.