This position statement from the Heart Failure Association of the European Society of Cardiology Cardio‐Oncology Study Group in collaboration with the International Cardio‐Oncology Society presents ...practical, easy‐to‐use and evidence‐based risk stratification tools for oncologists, haemato‐oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2‐targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi‐targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR‐ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.
Summary
Patients receiving targeted cancer treatments such as tyrosine kinase inhibitors (TKIs) have been classified in the clinically extremely vulnerable group to develop severe acute respiratory ...syndrome coronavirus‐2 (SARS‐CoV‐2), including patients with chronic myeloid leukaemia (CML) taking TKIs. In addition, concerns that immunocompromised individuals with solid and haematological malignancies may not mount an adequate immune response to a single dose of SARS‐CoV‐2 BNT162b2 (Pfizer‐BioNTech) vaccine have been raised. In the present study, we evaluated humoral and cellular immune responses after a first injection of BNT162b2 vaccine in 16 patients with CML. Seroconversion and cellular immune response before and after vaccination were assessed. By day 21 after vaccination, anti‐Spike immunoglobulin G was detected in 14/16 (87·5%) of the patients with CML and all developed a neutralising antibody response serum dilution that inhibits 50% infection (ID50) >50, including medium (ID50 of 200–500) or high (ID50 of 501–2000) neutralising antibodies titres in nine of the 16 (56·25%) patients. T‐cell response was seen in 14/15 (93·3%) evaluable patients, with polyfunctional responses seen in 12/15 (80%) patients (polyfunctional CD4+ response nine of 15, polyfunctional CD8+ T‐cell response nine of 15). These data demonstrate the immunogenicity of a single dose of SARS‐CoV‐2 BNT162b2 vaccine in most patients with CML, with both neutralising antibodies and polyfunctional T‐cell responses seen in contrast to patients with solid tumour or lymphoid haematological malignancies.
Summary
The search for novel targets in chronic myeloid leukaemia (CML) is ongoing, to improve treatment efficacy in refractory disease and increase eligibility for tyrosine kinase inhibitor (TKI) ...discontinuation. Increased frequency of Tregs and effector Tregs was evident at diagnosis, together with increased expression of T‐cell exhaustion markers, including in regulatory T cells at diagnosis and in patients with refractory disease. Plasma analysis revealed significantly increased levels of cytokines including tumour necrosis factor (TNF)‐a and interleukin (IL)‐6 at diagnosis, in keeping with a pro‐inflammatory state prior to treatment. We hence demonstrate T‐cell exhaustion and a pro‐inflammatory state at diagnosis in CML, likely secondary to leukaemia‐associated antigenic overload associated with increased disease burden.
Classical veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication post allogeneic hematopoietic stem cell transplantation (HSCT). Before the recently revised EBMT ...criteria, the Baltimore and modified Seattle criteria failed to recognize the syndrome of late‐onset VOD. We present real‐world experience from a large UK transplant center reporting on VOD/SOS in consecutive HSCT adult patients (n = 530), transplanted for hematological cancers. We identified 27 patients treated with Defibrotide for VOD/SOS diagnosis, where detailed data were available for final analysis. Using standard definitions including EBMT criteria, around 30% (n = 8/27) of cases classified as late‐onset VOD presenting at median of 46 (22‐93) days but with D100 survival (63% vs 58%, Log‐rank; P = 0.81) comparable to classical VOD. Hazard ratio for D100 mortality was 2.82 (95% CI: 1.74‐4.56, P < .001, Gray test) with all VOD/SOS events. Twenty percent (n = 2/8) of late‐onset VOD patients were anicteric and 42% (n = 8) classical VOD patients presented with refractory thrombocytopenia, while less than half met EBMT criteria for classical VOD in adults, highlighting gaps in real‐world diagnostic limitations using EBMT criteria. However, challenges remain about underrecognition and difficulties related to early defibrotide access for treatment of late‐onset VOD in current treatment guidelines. Our report strongly supports early Defibrotide for the treatment of severe VOD/SOS in adults regardless of time of onset.
Late‐onset veno‐occlusive disease, defined as occurring beyond 21 days after allogeneic haematopoietic stem cell transplant, remains a significant yet under‐recognized problem, accounting for nearly one‐third of cases and showing equivalent outcomes following defibrotide treatment compared to the classic form.
Patients with haematological malignancies (HM) face high rates of intensive care unit (ICU) admission and mortality. High-flow nasal cannula oxygen (HFNCO) is increasingly used to support HM patients ...in ward settings, but there is limited evidence on the safety and efficacy of HFNCO in this group. We retrospectively reviewed all HM patients receiving ward-based HFNCO, supervised by a critical care outreach service (CCOS), from January 2014 to January 2019. We included 130 consecutive patients. Forty-three (33.1%) were weaned off HFNCO without ICU admission. Eighty-seven (66.9%) were admitted to ICU, 20 (23.3%) required non-invasive and 34 (39.5%) invasive mechanical ventilation. ICU and hospital mortality were 42% and 55% respectively. Initial FiO
2
< 0.4 (OR 0.27, 95% CI 0.09–0.81,
p
= 0.019) and HFNCO use on the ward > 1 day (OR 0.16, 95% CI 0.04, 0.59,
p
= 0.006) were associated with reduced likelihood for ICU admission. Invasive ventilation was associated with reduced survival (OR 0.27, 95%CI 0.1–0.7,
p
= 0.007). No significant adverse events were reported. HM patients receiving ward-based HFNCO have higher rates of ICU admission, but comparable hospital mortality to those requiring CCOS review without respiratory support. Results should be interpreted cautiously, as the model proposed depends on the existence of CCOS.
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