REVIEW HEMATOLOGY

Adult T-cell leukaemia-lymphoma: Pathogeny and clinical recommendations

SUMMARY

Human T-cell leukaemia virus type 1 (HTLV-1) was the first human oncogenic virus discovered. It is endemic in some regions of the world but increasingly prevalent in our countries as globalisation is progressing. After several decades of asymptomatic carrying, approximately 2–5% of infected individuals will develop adult-T-cell leukaemia-lymphoma (ATL). Despite significant progress in the physiopathology and therapeutic interventions, the prognosis of this rare disease is dismal. An update of classification, clinical features, diagnosis and recent treatment recommendations is outlined in this review.

(BELG J HEMATOL 2019;10(7):277–84)

Targeted next generation DNA sequencing for the detection of clonal haematopoiesis in idiopathic cytopaenia of undetermined significance (ICUS)

SUMMARY

Patients lacking diagnostic criteria for myelodysplastic syndrome, but who show an unexplained persistent cytopaenia are classified as patients suffering from idiopathic cytopaenia of undetermined significance (ICUS). A fraction of these patients carry somatic mutations in genes which are also mutated in myeloid neoplasms. The significance of these mutations in ICUS patients is not well known and only few research papers have tried to correlate them with clinical outcome. ICUS patients carrying somatic mutations seem to have a higher progression rate to myeloid malignancies compared to unmutated patients. Some mutation profiles also show lower overall survival, similar to patients with (low-risk) myelodysplastic syndrome. Therefore, it seems useful to screen for somatic mutations in cytopaenic patients. The goal of this paper is to review recent literature regarding the significance of somatic mutations in cytopaenic patients and propose a screening protocol by evaluating a test protocol at the AZ Sint-Jan hospital Brugge-Oostende.

(BELG J HEMATOL 2019;10(6):231–40)

Defeating cytomegalovirus, the transplantation troll: can letermovir do the job?

Letermovir (AIC246, MK-8228) is a novel anti-cytomegalovirus (CMV) agent that inhibits CMV replication by targeting the viral terminase complex. In December 2017, letermovir was approved by the Food and Drug Administration (FDA) for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogenic haematological stem cell transplantation. Letermovir shows a favourable pharmacokinetic profile in haematological stem cell transplantation recipients after oral administration. The recommended dose for CMV-prophylaxis is once daily 480 mg (oral or intravenous). Letermovir demonstrated superiority in a placebo (plus polymerase chain reaction-monitoring and pre-emptive therapy)-controlled phase III randomised clinical trial. Letermovir is an inhibitor of the cytochrome P450 (CYP)3A family, CYP2B8 and an inducer of the CYP2C9/19. Dose-adjustments (240 mg/day) are necessary when letermovir is combined with cyclosporine. Combinations of letermovir with either voriconazole, midazolam and rosiglitazone require close monitoring of the plasma levels of the latter agents. Letermovir-resistant CMV mutants share mutations that are mostly located between the codon range 230–370 of the UL56 gene. Letermovir is not nephrotoxic nor myelotoxic, but slightly higher rates of atrial fibrillation and tachycardia have been described. In conclusion, letermovir is the first FDA approved anti-CMV agent for prophylaxis in haematological stem cell transplantation patients.

(BELG J HEMATOL 2019;10(4):136–45)

Acquired haemophilia A

Acquired haemophilia A is a potentially severe condition characterised by spontaneous bleeding episodes. Direct recognition and prompt treatment are mandatory. Diagnostic coagulation assays show an isolated prolonged activated partial thromboplastin time, not correcting in a mixing assay. An isolated decrease of factor VIII activity together with the presence of a neutralising antibody confirm the diagnosis. Treatment consists of cessation of a possible bleed and the eradication of the neutralising antibody.

(BELG J HEMATOL 2019;10(4):146–52)

Causes, diagnosis and management of congenital or acquired neutropaenia

Neutropaenia is a common incidental finding on routine blood studies. This manuscript will focus on the possible causes, challenging differential diagnosis and appropriate management of neutropaenia. Different mechanisms may explain a decreased production, impaired development or increased destruction of neutrophilic granulocytes. We distinguish between congenital and acquired causes. The former includes benign ethnic neutropaenia, severe congenital neutropaenia and cyclic neutropaenia. For the latter, infections, drugs, auto-immune reactions, nutritional deficiencies as well as haematological malignancies are all possible reasons of neutropaenia. The risk of infection in those with non-chemotherapy-induced neutropaenia mainly depends on the bone marrow reserve. Asymptomatic patients with mild or moderate neutropaenia can be observed with serial blood counts at increasing intervals. Infections should always be treated according to the severity of neutropaenia. Therapy with growth factors, drug discontinuation and immunosuppressive therapy can be considered depending on the underlying cause.

(BELG J HEMATOL 2019;10(3):103–12)

Clinical and biologic correlates of frailty in older patients with malignant hemopathies

Frailty assessment in older patients with malignant hemopathies is very useful in order to improve care and treatment options. However, some lacks of data exist regarding the unsuspected frail population in presumed ‘clinically fit’ patients who should not benefit from chemotherapy. In this article, we review current data regarding prognostic factors and frailty scoring in older patients with malignant hemopathies. Prospective trials are needed to build a new frailty scoring to assess the unsuspected frail population in ‘clinically fit’ patients including specifically assessment of cognitive impairment.

(BELG J HEMATOL 2019;10(2):65–8)

Diffuse large B-cell lymphoma refractory to R-CHOP

SUMMARY

Rituximab with cyclophosphamide, adriamycin, vincristine and prednisone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma and is able to cure 50–60% of the patients. However, patients resistant to or in early relapse after R-CHOP have a very poor prognosis with a median overall survival of only six months, and very few patients have a long survival. Double-hit lymphoma (rearrangement MYC and BCL2) has a major risk of refractoriness, and more intense chemotherapy than R-CHOP is recommended. Early PET-CT could identify resistance to conventional chemotherapy. Intensification with autologous or allogeneic stem cell transplantation is recommended in case of a response to salvage regimen. New agents are expected and chimeric antigen receptor T-cell therapy is a very promising approach.

(BELG J HEMATOL 2018;9(7):249–53)