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Br J Haematol ; 197(2): 171-187, 2022 04.
Article in English | MEDLINE | ID: covidwho-1822046


SCOPE: The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with Waldenström macroglobulinaemia. In individual patients, circumstances may dictate an alternative approach. METHODOLOGY: This guideline was compiled according to the British Society for Haematology (BSH) process at Recommendations are based on a review of the literature using Medline, Pubmed, Embase, Central, Web of Science searches from beginning of 2013 (since the publication of the previous guidelines) up to November 2021. The following search terms were used: Waldenström('s) macroglobulin(a)emia OR lymphoplasmacytic lymphoma, IgM(-related) neuropathy OR cold h(a)emagglutinin disease OR cold agglutinin disease OR cryoglobulin(a)emia AND (for group a only) cytogenetic OR molecular OR mutation OR MYD88 OR CXCR4, management OR treatment OR transfusion OR supportive care OR plasma exchange OR plasmapheresis OR chemotherapy OR bendamustine OR bortezomib OR ibrutinib OR fludarabine OR dexamethasone OR cyclophosphamide OR rituximab OR everolimus, bone marrow transplantation OR stem cell transplantation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haemato-Oncology Task Force, the BSH Guidelines Committee and the Haemato-Oncology sounding board of BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by UK Charity WMUK; these organisations do not necessarily approve or endorse the contents.

Hematology , Waldenstrom Macroglobulinemia , Bendamustine Hydrochloride/therapeutic use , Bortezomib/therapeutic use , Humans , Rituximab/therapeutic use , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/therapy
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318752


Background: B cell chronic lymphocytic leukaemia (CLL) is associated with immune suppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination.Methods: We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 13 patients underwent a standard interval (3-week) vaccine regimen whilst 286 underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. 267 samples were taken at 5 weeks after the first vaccine for patients on the extended interval regimen and 13 and 42 samples were taken at 2-4 weeks after the second vaccine in patients on the standard or extended vaccine regimens respectively.Findings: Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine, compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine.Interpretation: Antibody responses after both the first and second Covid-19 vaccine are lower in patients with CLL compared to age-matched donors. This is particularly marked in patients who are taking BTK inhibitors or have serum IgA deficiency. Further approaches such as repeat vaccination or administration of prophylactic antibody may be worthy of investigation for some patients. Funding Information: This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.Declaration of Interests: None to declare. Ethics Approval Statement: The work was performed under the CIA UPH IRAS approval (REC 20W\0240) and conducted according to the Declaration of Helsinki and good clinical practice. Ethical approval was obtained from North West Preston Research Ethics Committee with favourable outcome. Informed consent was obtained in person or by remote consultation.

EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295697


Background: Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL) and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses.<br><br>Method: We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with 2 different vaccine platforms.<br><br>Results: Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n=204) or adenovirus-based (n=296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months-post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination.<br><br>Interpretation: These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoral protection against the globally-dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.<br><br>Funding Information: This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.<br><br>Declaration of Interests: The authors declare no conflicts of interest.<br><br>Ethics Approval Statement: Informed consent was obtained by remote consultation and work performed under the CIA UPH IRAS approval (REC 20W\0240) from North-West and Preston ethics committee and conducted according to the Declaration of Helsinki.<br>