LGLL is a lymphoproliferative disorder that is known to be associated with autoimmune conditions, such as rheumatoid arthritis and Sjogren's syndrome. To our knowledge, it has only been reported once in association with AHA. This case would be the second of such report of LGLL as a potential cause of AHA [2]. While our predecessors managed bleeding using bypassing agents, our choice varied based on the patient's age and comorbidities [2]. Hemostasis in AHA can be achieved by administering FVIII bypassing agents in the form of recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (aPCC) which can generate thrombin in a non-physiologic fashion, independent of FVIII. A practical limitation of these products is that their activity cannot be monitored with standard coagulation assays and they carry an increased risk of thrombosis, particularly in older individuals with vascular co-morbidities. Recombinant porcine FVIII (rPorcine FVIII) is an alternative hemostatic agent for AHA since it is quite different from human FVIII and is not recognized by the autoantibody in most cases, thus allowing the coagulation cascade to proceed in a normal physiologic fashion. An advantage of this is that it can be measured by checking FVIII activity, thereby allowing it to be measured to maintain an activity that minimizes the risk of both bleeding due to sub-therapeutic levels and thrombosis from supra-therapeutic levels. Due to this, we prefer rPorcine FVIII over bypassing agents especially in older patients with cardiovascular comorbidities [3]. While there are no head-to-head comparison studies between the two, the decision is usually based on the availability, prior case-to-case experience, and economic considerations. Immunosuppressive therapy (IST) is recommended in all adults with AHA to achieve FVIII inhibitor eradication as the bleeding-related morbidity and mortality is substantial. In multiple studies and meta-analyses, it was found that combination IST (corticosteroids, cyclophosphamide, and rituximab) was superior to corticosteroids alone [3]. Our patient had LGLL as a potential underlying trigger for the development of AHA. Usually, this is an indolent neoplasm not requiring specific management other than watchful observation. However, concurrence with AHA and the patient’s age necessitated chemotherapy with cyclophosphamide. Other instances where LGLL requires treatment are severe neutropenia (absolute neutrophil count or ANC<0.5×10/L), moderate neutropenia (ANC>0.5×10/L) with superinfections, autoimmune conditions needing treatment, and transfusion-dependent anemia [5]. In summary, our case is the second report in the literature on AHA occurring in association with LGLL. Also, the discussion of our therapeutic choice for hemostasis presents nuances in the management of AHA in the elderly and those with cardiovascular comorbidities. Nishant R. Tiwari, Kaustubh S. Chaudhari, Vrushab Rao, Vivek R. Sharma Department of Internal Medicine, Byramjee Jeejeebhoy Medical College, Jagtap Clinic and Research Center, Pune, Bangalore Medical College and Research Institute, Bangalore, India, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

An illustrative case of B-cell prolymphocytic leukemia.

Inhibition Of The JAK/STAT Signaling Pathway As a Novel Therapy In CD8+ T-Large Granular Lymphocyte Leukemia

REFERENCES 1. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon, France: IARC Press, 2017. 2. Dearden C. How I treat prolymphocytic leukemia. Blood 2012;120:538-51. 3. Matutes E, Owusu-Ankomah K, Morilla R, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 1994;8:1640-5. 4. Sandes AF, de Lourdes Chauffaille M, Oliveira CR, et al. CD200 has an important role in the differential diagnosis of mature B-cell neoplasms by multiparameter flow cytometry. Cytometry B Clin Cytom 2014;86:98-105. 5. Chapiro E, Pramil E, Diop M, et al. Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53. Blood 2019;134:1821-31. 6. Kay NE, Hanson CA. B-cell prolymphocytic leukemia has 3 subsets. Blood 2019;134:1777-8. 7. Springael C, Delrieu V, Wu KL, et al. BHS guidelines for the treatment of large granular lymphocyte and chronic prolymphocytic leukaemias. Belg J Hematol 2016;7:103-11. 8. Gordon MJ, Raess PW, Young K, Spurgeon SEF, Danilov AV. Ibrutinib is an effective treatment for B-cell prolymphocytic leukaemia. Br J Haematol 2017;179:501-3. 9. Eyre TA, Fox CP, Boden A, et al. Idelalisib-rituximab induces durable remissions in TP53 disrupted B-PLL but results in significant toxicity: updated results of the UK-wide compassionate use programme. Br J Haematol 2019;184:667-71. 10. Wang HY, Zu Y. Diagnostic algorithm of common mature B-cell lymphomas by immunohistochemistry. Arch Pathol Lab Med 2017;141:1236-46. 11. Coelho H, Badior M, Melo T. Sequential kinase inhibition (Idelalisib/Ibrutinib) induces clinical remission in B-cell prolymphocytic leukemia harboring a 17p deletion. Case Rep Hematol 2017;2017:8563218. 12. Bindra BS, Kaur H, Portillo S, Emiloju O, Garcia de de Jesus K. B-cell prolymphocytic leukemia: case report and challenges on a diagnostic and therapeutic forefront. Cureus 2019;11:e5629. 13. Hew J, Pham D, Matthews Hew T, Minocha V. A novel treatment with obinutuzumab-chlorambucil in a patient with B-cell prolymphocytic leukemia: a case report and review of the literature. J Investig Med High Impact Case Rep 2018;6:2324709618788674. Rapid resolution of bone marrow necrosis mimicking relapse of pediatric acute lymphoblastic leukemia

Rapid resolution of bone marrow necrosis mimicking relapse of pediatric acute lymphoblastic leukemia

Large granular lymphocyte and prolymphocytic leukaemias are rare chronic lymphoproliferative disorders. Large granular lymphocyte leukaemias consist of indolent disorders such as T-cell large granular lymphocyte and chronic lymphoproliferative disorder of natural killer cells and the very rare but aggressive natural killer cell leukaemia. Treatment of the indolent large granular lymphocyte leukaemias is necessary in case of symptomatic cytopaenias or non-haematological autoimmune disorders. First line therapy of these two disorders is based on three immunosuppressive drugs: methotrexate, cyclophosphamide and cyclosporine A. Aggressive natural killer cell leukaemia needs an L-asparaginase containing regimen as induction followed by allogeneic stem cell transplantation to prolong remission. T-cell prolymphocytic leukaemia always follows an aggressive course even after an indolent onset. The optimal treatment strategy should exist of remission induction with alemtuzumab intravenously followed by autologous or allogeneic stem cell transplantation. Treatment indications for B-cell prolymphocytic leukaemia follow the criteria described by the chronic lymphocytic leukaemia guidelines. After induction with fludarabine, cyclophosphamide, rituximab or bendamustine in patients without a p53 mutation and/or a 17p deletion and alemtuzumab in case of a p53 mutation and/or a 17p deletion, stem cell transplantation must be considered. (Belg J Hematol 2016;7(3):103-11)

BHS guidelines for the treatment of large granular lymphocyte and cronic prolymphocytic leukaemias

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BHS guidelines for the treatment of large granular lymphocyte and cronic prolymphocytic leukaemias