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Fulltext Post-transplant lymphoproliferative disorder presenting as T-prolymphocytic leukemia: a case report

Kasinathan G, Kori AN, Azmie NM

J Med Case Rep, 2019 Jul 22;13(1):223.
PMID: 31327318 DOI: 10.1186/s13256-019-2164-y

INTRODUCTION: Post-transplant lymphoproliferative disorder is a serious disorder which occurs post hematopoietic stem cell transplant or solid organ transplantation. T-prolymphocytic leukemia is a T cell type monomorphic post-transplant lymphoproliferative disorder which accounts for only 2% of all mature lymphocytic leukemias in adults over the age of 30.
CASE PRESENTATION: A 59-year-old man of Chinese ethnicity presented to our hematology unit with headache, lethargy, and exertional dyspnea for the past 1 month. He underwent an uneventful cadaveric renal transplant 20 years ago for chronic glomerulonephritis-induced end-stage renal disease. He had been on long-term immunosuppressants since then consisting of orally administered prednisolone 10 mg daily and orally administered cyclosporine A 50 mg twice daily. On examination, he was pale with a palpable liver and spleen. He had a functioning renal graft. Marrow flow cytometry confirmed T-prolymphocytic leukemia with lymphocytes expressing CD2, CD3, CD7, CD52, and TCL-1. His human T-cell lymphotropic virus and Epstein-Barr virus serology and deoxyribonucleic acid (DNA) were negative. He was treated with one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy to which he failed to respond. In view of his renal allograft, he was not suitable for alemtuzumab due to the risk of nephrotoxicity. He was given orally administered venetoclax but he died on day 17 due to severe auto tumor lysis syndrome.
CONCLUSION: The place of immunophenotyping in the diagnosis and treatment of this disorder is of significant importance. More research needs to be carried out to further comprehend the pathophysiology and treatment modalities for this disorder.
Fulltext Challenging lymphoid malignancy of primary central nervous system lymphoma: A case report

Kasinathan G, Kori AN, Hassan N

Ann Med Surg (Lond), 2020 Sep;57:307-310.
PMID: 32874561 DOI: 10.1016/j.amsu.2020.08.011

Introduction: Primary central nervous lymphoma is an aggressive disease without evidence of systemic spread with an annual incidence of 7 cases per 1,000,000 people in the United States.
Case presentation: A 68-year-old gentleman of Malay ethnicity presented with left sided weakness associated with reduced sensation for one month. The patient was healthy and denied any constitutional symptoms, joint pains, rash or seizures. There was no recent trauma. Physical examination revealed left upper and lower limb motor grade power of 3/5 with upper motor neurone weakness of the left facial nerve. He had brisk reflexes and an upgoing extensor plantar response. Brain imaging (Magnetic Resonance Imaging) showed two lesions: one occupying the right head of the caudate nucleus and the other seen at the right side of the body of the corpus callosum. Histomorphology and immunohistochemistry confirmed Diffuse Large B-Cell Lymphoma (DLBCL) of non-germinal center type. He was treated with De Angelis protocol which involves chemoradiotherapy consisting of high dose methotrexate and whole brain radiotherapy (WBRT), followed by high dose cytarabine. Brain imaging post chemoradiation showed complete remission.
Conclusion: Prompt detection with appropriate therapeutic protocol could significantly minimise the permanent neurological deficits in patients with this rare and challenging lymphoid malignancy.
Fulltext Abdominal Lymphocyte-Depleted Hodgkin Lymphoma: A Rare Presentation

Kasinathan G, Kori AN, Hassan N

Int J Gen Med, 2019;12:405-409.
PMID: 31807052 DOI: 10.2147/IJGM.S232254

Background: Hodgkin lymphoma (HL) is a type of lymphoma that arises from the B lymphocytes. The four main subtypes of HL are the nodular sclerosing, mixed cellularity, lymphocyte rich and the lymphocyte depleted. Nodular sclerosis subtype accounts for majority of all classical HL, whereas lymphocytic depletion type accounts for less than 1%. The main objective of reporting this case is to share with the medical fraternity a rare presentation of abdominal lymphocyte-depleted classical Hodgkin lymphoma.
A 47-year-old gentleman of Malay ethnicity with no known pre-morbidities, presented to the haematology unit with a 2-month history of night fever, loss of weight, malaise, anorexia and abdominal swelling. Abdominal examination revealed a periumbilical and lower epigastric swelling measuring 6x6 cms. The swelling was non-tender, firm in consistency and smooth on palpation. The Contrast Enhanced Computed Tomography (CECT) imaging revealed an enlarged mesenteric mass measuring 5.8x6.9x5.7 cm and multiple enlarged aorta-caval lymph nodes. The mesenteric tumour histology and immunohistochemistry were consistent with lymphocyte depleted HL. He completed six cycles of intravenous ABVD polychemotherapy consisting of doxorubicin (Adriamycin) 25mg/m2, Bleomycin 10mg/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2. The Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET /CT) imaging post 2 cycles and 6 cycles of ABVD polychemotherapy showed complete metabolic response to chemotherapy.
Conclusion: Lymphocyte-depleted classical Hodgkin lymphoma (LDcHL) is a rare entity and is mostly diagnosed at a later stage rendering it a disease with poor prognostic outcomes. Early detection and prompt institution of therapy is crucial in the management of this disease.
Fulltext Cancer-Associated Thrombosis: A Clinical Scoping Review of the Risk Assessment Models Across Solid Tumours and Haematological Malignancies

Mosaad M, Elnaem MH, Cheema E, Ibrahim I, Ab Rahman J, Kori AN, et al.

Int J Gen Med, 2021;14:3881-3897.
PMID: 34335052 DOI: 10.2147/IJGM.S320492

Cancer-associated thrombosis (CAT) is a leading cause of death in cancer patients receiving outpatient chemotherapy. The latest guidelines emphasize stratifying the patients in terms of CAT risks periodically. Multiple risk assessment models (RAMs) were developed to classify patients and guide thromboprophylaxis to high-risk patients. This study aimed to discuss and highlight different RAMs across various malignancy types with their related advantages and disadvantages. A scoping review was conducted using predefined search terms in three scientific databases, including Google Scholar, Science Direct, and PubMed. The search for studies was restricted to original research articles that reported risk assessment models published in the last thirteen years (between 2008 and 2021) to cover the most recently published evidence following the development of the principal risk assessment score in 2008. Data charting of the relevant trials, scores, advantages, and disadvantages were done iteratively considering the malignancy type. Of the initially identified 1115 studies, 39 studies with over 67,680 patients were included in the review. In solid organ malignancy, nine risk assessment scores were generated. The first and most known Khorana risk score still offers the best available risk assessment model when used for high-risk populations with a threshold of 2 and above. However, KRS has a limitation of failure to stratify low-risk patients. The COMPASS-CAT score showed the best performance in the lung carcinoma patients who have a higher prevalence of thrombosis than other malignancy subtypes. In testicular germ cell tumours, Bezan et al RAM is a validated good discriminatory RAM for this malignancy subtype. CAT in haematological malignancy seems to be under-investigated and has multiple disease-related, and treatment-related confounding factors. AL-Ani et al score performed efficiently in acute leukemia. In multiple myeloma, both SAVED and IMPEDED VTE scores showed good performance. Despite the availability of different disease-specific scores in lymphoma-related thrombosis, the standard of care needs to be redefined.
A randomized double blind control trial comparing filgrastim and pegfilgrastim in cyclophosphamide peripheral blood hematopoietic stem cell mobilization

Kuan JW, Su AT, Wong SP, Sim XY, Toh SG, Ong TC, et al.

Transfus Apher Sci, 2015 Oct;53(2):196-204.
PMID: 25910537 DOI: 10.1016/j.transci.2015.03.017

There are few randomized trials comparing filgrastim and pegfilgrastim in peripheral blood stem cell mobilization (PBSCM). None of the trials studied the effects of the timing of pegfilgrastim administration on the outcomes of mobilization. We conducted a randomized triple blind control trial comparing the outcomes of filgrastim 5 µg/kg daily from day 3 onwards, 'early' pegfilgrastim 6 mg on day 3 and 'delayed' pegfilgrastim 6 mg on day 7 in cyclophosphamide PBSCM in patients with no previous history of mobilization. Peripheral blood (PB) CD34+ cell count was checked on day 8 and day 11 onward. Apheresis was started when PB CD34+ ≥ 10/µl from day 11 onward. The primary outcome was the successful mobilization rate, defined as cumulative collection of ≥2 × 10(6)/kg CD34+ cells in three or less apheresis. The secondary outcomes were the day of neutrophil and platelet engraftment post transplantation. There were 156 patients randomized and 134 patients' data analyzed. Pegfilgrastim 6 mg day 7 produced highest percentage of successful mobilization, 34 out of 48 (70.8%) analyzed patients, followed by daily filgrastim, 28 out of 44 (63.6%) and day 3 pegfilgrastim, 20 out of 42 (47.6%) (p = 0.075). Pegfilgrastim day 7 and daily filgrastim reported 1.48 (p = 0.014) and 1.49 (p = 0.013) times higher successful mobilization rate respectively as compared to pegfilgrastim day 3 after adjusting for disease, gender and exposure to myelotoxic agent. Multiple myeloma patients were three times more likely to achieve successful mobilization as compared to acute leukemia or lymphoma patients. Pegfilgrastim avoided the overshoot of white cells compared to filgrastim. There was no difference in the duration of both white cells and platelet recovery post transplantation between the three interventional arms.