REVIEW HEMATOLOGY

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)

Extracorporeal photochemotherapy for graft-versus-host disease: Where we are now and where we are going!

SUMMARY

Graft-versus-host disease remains the leading cause of morbidity, non-relapse mortality and treatment failure after allogeneic haematopoietic stem cell transplantation. So far, steroids are the first line treatment, but around 40% of patients become steroid-resistant or fail to respond at a safe dose. Patients who fail to respond to the initial therapy have a dismal prognosis, and no standard treatment is well established for them to date. Treatments that modulate the immune system rather than directly suppressing its function, although not dampening a potential graft-versus-malignancy effect, would therefore be highly desirable, and extracorporeal photopheresis appeared as being a good candidate to fill in these criteria. Multiple reports of treatments in both paediatric and adult patients with graft-versus-host disease have been published, and the overall favourable profile compared with other available immunosuppressive therapies continues to make extracorporeal photopheresis appealing despite all of the unknowns. In this article, we review the use of extracorporeal photopheresis for the treatment of graft-versus-host disease, including technical aspects, mechanism of action, safety profile and clinical efficacy data.

(BELG J HEMATOL 2018;9(7):254–65)

State of the Art I: Thrombosis

The first state of the art session of the 2018 annual BSTH meeting focused on thrombosis. While Dr. Anna Falanga (Hopsital Papa Giovanni XXIII, Bergamo, Italy) and Dr. Cihan Ay (Medical university of Vienna, Austria) specifically addressed the close relationship between thrombosis and cancer, Dr. Walter Ageno (Ospedale di Circolo, Varese, Italy) discussed the practicalities of managing splanchnic (SVT) and cerebral vein thrombosis (CVT).