REVIEW HEMATOLOGY

Acute graft-versus-host disease: diagnosis, pathophysiology and prevention

SUMMARY

Acute graft-versus-host disease (aGVHD) remains a severe complication after allogeneic stem cell transplantation (alloHCT). It is a disregulated immune process, during which the immune cells of the donor attack the healthy tissues in the immunocompromised host. Over the past two decades, progress in understanding its pathophysiology have helped redefine aGVHD reactions and clinical presentations. Typically, the disease presents with serious inflammatory lesions mainly in the skin, gut and liver. Its severity is assessed by gathering clinical signs and dysfunctions of each organ. Despite standard prophylaxis regimens, aGVHD still occurs in approximately 30–60% of transplanted patients and remains a major cause of transplant-related morbidity and mortality. Hence, there is an urgent need for optimising preventive strategies. In this review, we give insights on how to make an accurate diagnosis and scoring assessment of aGVHD, propose a short overview of the current knowledge about its immunobiology and discuss the current and developing strategies for prevention.

(BELG J HEMATOL 2020;11(4):159–173)

Big Children or Small Adults? Leukaemia Treatment in Adolescence and Young Adulthood

SUMMARY

The outcome of adolescents and young adults (AYAs) with acute lymphoblastic leukaemia (ALL) has improved dramatically over the last decades by using paediatric and paediatric-inspired protocols in this age group. The outcome of different paediatric, paediatric-inspired and adult-based regimens are compared in this review. Despite pre-existing fear among clinicians to use these high-intensity paediatric regimens in AYAs, toxicities seem manageable, with treatment-related mortality comparable to that seen with adult protocols. In paediatric protocols, the use of allogeneic stem cell transplantation is restricted to certain high-risk groups and prophylactic cranial irradiation is omitted. In recent years, evaluation of minimal residual disease is increasingly used as prognostic marker and as a tool to guide therapy. In Philadelphia-positive ALL, the use of tyrosine-kinase inhibitors has completely changed prognosis and therapeutic decisions.

(BELG J HEMATOL 2020;11(3):88–97)

Big Children or Small Adults? Acute Myeloid Leukaemia (AML) Treatment in Adolescence and Young Adulthood

SUMMARY

Adolescents and young adults (AYAs), aged 15 to 39 years, with newly diagnosed acute myeloid leukaemia (AML) differ from both younger and older patients in terms of patient-specific as well as disease-specific factors. The improvement in outcome over time for this group is noticeably less than for their younger and older counterparts. Reasons for this are thought to be lack of standardisation of therapy, being treated with either adult or paediatric regimens, low trial participation and specific psychosocial factors. In this article, we review the distinct characteristics of AYA AML in order to address this issue and conclude that an AYA-specific approach and research are warranted to overcome stagnating outcome results.

(BELG J HEMATOL 2020;11(3):98–101)

Bone Marrow Microenvironment-Induced Resistance to Immunotherapeutic Agents in Multiple Myeloma

SUMMARY

Over the past decades, immunotherapy has significantly improved the overall survival of multiple myeloma (MM) patients. In addition to immunomodulatory drugs and targeted antibodies that are currently standard of care, novel promising immunotherapeutic approaches, such as bispecific antibodies and chimeric antigen receptor-transduced T-cells (CAR T-cells) are being increasingly tested in clinical trials. Nonetheless, similar to what has been seen in chemotherapy, MM is also capable of developing resistance against immunotherapy. Direct and indirect interactions between MM and the MM bone marrow microenvironment (BM-ME) enable MM-cells to escape not only from chemotherapy but also from immunotherapy. This review will discuss how BM-ME enables MM-cells to evade the immune system and immunotherapy via immunosuppression and via induction of genuine resistance against cytotoxic mechanisms of immune killer cells.

(BELG J HEMATOL 2020;11(3):102–7)

Fertility preservation in women before cancer therapy

SUMMARY

In recent decades, major progress has been made in cancer diagnosis and therapy, significantly extending the life expectancy of cancer patients and thereby dramatically increasing demand for fertility preservation. Indeed, of all cancers arising in women worldwide, ~15% occur in those aged <45 years, while ~40% of cancers affecting girls <20 years of age are of haematological origin. Furthermore, patients requiring chemotherapy and/or radiotherapy are at risk of premature ovarian failure. This review discusses different strategies aiming to preserve and protect fertility: embryo and oocyte cryopreservation; ovarian tissue cryopreservation; fertility-sparing surgery; gonadoprotective strategies; and new avenues of research like the artificial ovary and in vitro maturation of primordial follicles.

(BELG J HEMATOL 2020;11(2):44–8)

Recent advances in the genomic and epigenomic biology of juvenile myelomonocytic leukaemia

SUMMARY

Juvenile myelomonocytic leukaemia is a heterogeneous disease caused by constitutional activation of the Ras signal transduction pathway. The clinical course of the disease is variable and non-specific. In the majority of patients prompt hematopoietic stem cell transplantation is necessary for long-term survival, whereas in a minority the disease will resolve without treatment. In more than 90% of the patients, mutations in one or more of the following genes can be found (somatic NRAS, KRAS and PTPN11, germline NF1 and CBL). However, these canonical mutations are insufficient to explain the phenotypic heterogeneity of this disease. More recently, secondary mutations, non-coding RNA expression, and genomic DNA methylation have led to a better understanding of the pathobiology of the disease, and shown to play a role in the classification and prognostication of this rare disease. In addition, this novel information has been crucial for novel drug development and introduction of novel patient-tailored therapies, which are currently being tested in vitro or in vivo in clinical trials.
(BELG J HEMATOL 2020;11(2):49–55)

A single-center retrospective study of patients with systemic mastocytosis at University Hospital Leuven

SUMMARY

Systemic mastocytosis is a rare heterogeneous disorder characterised by abnormal proliferation of mast cells. It can be divided in subtypes with different phenotypes and prognoses. This article is a retrospective descriptive study of 37 patients with systemic mastocytosis according to the WHO criteria of 2008 at UZ Leuven. Twenty-eight patients had indolent systemic mastocytosis (75.7%), four smouldering systemic mastocytosis (10.8%), three aggressive systemic mastocytosis (8.1%) and two systemic mastocytosis with associated haematological neoplasia (5.4%). In one out of five patients, the diagnosis was made based on at least three minor criteria. The sensitivity of CD25 expression was 100%. In 75.7% a KITD816V mutation was detected. The value of serum tryptase was associated with the subtype of systemic mastocytosis. Seventy-eight percent had cutaneous lesions. Forty-eight percent experienced at least one anaphylactic reaction. Osteoporosis was reported in 24.6%. Eighty-nine percent and 64.9% of patients were treated with respectively H1 and H2 antihistamines. Cytoreductive treatment was administered to nine patients (24.3%). Three patients received as first-line treatment midostaurine, three imatinib, one cladribine, one nilotinib and one masitinib. This study reflects the heterogeneity of this condition and emphasises the importance of a multidisciplinary approach in a specialised center for early diagnosis and treatment of disease-associated manifestations.

(BELG J HEMATOL 2019;10(7):265–76)