In this large single-centre study, we report high prevalence (25%) of, small (<10%) and very small (<1%), paroxysmal nocturnal hemoglobinuria (PNH) clones by high-sensitive cytometry among 3085 ...patients tested. Given PNH association with bone marrow failures, we analyzed 869 myelodysplastic syndromes (MDS) and 531 aplastic anemia (AA) within the cohort. PNH clones were more frequent and larger in AA vs. MDS (p = 0.04). PNH clone, irrespective of size, was a good predictor of response to immunosuppressive therapy (IST) and to stem cell transplant (HSCT) (in MDS: 84% if PNH+ vs. 44.7% if PNH-, p = 0.01 for IST, and 71% if PNH+ vs. 56.6% if PNH- for HSCT; in AA: 78 vs. 50% for IST, p < 0.0001, and 97 vs. 77%, p = 0.01 for HSCT). PNH positivity had a favorable impact on disease progression (0.6% vs. 4.9% IPSS-progression in MDS, p < 0.005; and 2.1 vs. 6.9% progression to MDS in AA, p = 0.01), leukemic evolution (6.8 vs. 12.7%, p = 0.01 in MDS), and overall survival 73% (95% CI 68-77) vs. 51% (48-54), p < 0.0001, with a relative HR for mortality of 2.37 (95% CI 1.8-3.1; p < 0.0001) in PNH negative cases, both in univariate and multivariable analysis. Our data suggest systematic PNH testing in AA/MDS, as it might allow better prediction/prognostication and consequent clinical/laboratory follow-up timing.
CD4
T-follicular helper cells are essential for the survival, proliferation, and differentiation of germinal center B cells and have been implicated in the pathogenesis of follicular lymphoma (FL). ...To further define the role of these cells in FL, we used multiparameter confocal microscopy to compare the architecture of normal and neoplastic follicles and next generation sequencing to analyze the T-cell receptor repertoire in FL lymph nodes (LN). Multiparameter analysis of LN showed that the proportion of T-follic-ular helper cells (T
) in normal and neoplastic follicles is the same and that the previously reported increase in T
numbers in FL is thus due to an increase in the number and not content of follicles. As in normal germinal centers, T
were shown to have a close spatial correlation with proliferating B cells in neoplastic follicles, where features of immunological synapse formation were observed. The number of T
in FL correlate with the rate of B-cell proliferation and T
co-localized to activation induced cytidine deaminase expressing proliferating B cells. T-cell receptor repertoire analysis of FL LN revealed that follicular areas are significantly more clonal when compared to the rest of the LN. These novel findings show that neoplastic follicles and germinal centers share important structural features and provide further evidence that T
may play a role in driving B-cell proliferation and genomic evolution in T
Our results also suggest that targeting this interaction would be an attractive therapeutic option.
Background & Aims:
Budd–Chiari Syndrome (BCS) results from obstruction to hepatic venous outflow, with myeloproliferative disorder (MPD) accounting for up to 40% of cases. A number of BCS cases ...labelled as “idiopathic” do not fulfill the diagnostic criteria for MPD but have features suggestive of a latent form based on hyperplastic bone marrow and erythroid progenitor cell culture; these cases may subsequently develop overt MPD. A clonal mutation in
JAK2 tyrosine kinase (
JAK2V617F) occurs in a high proportion of patients with MPD and is of use in the characterization of latent MPD in BCS.
Methods:
We performed allele-specific polymerase chain reaction to screen for
JAK2V617F in subjects with BCS (n = 41) and polycythemia vera (PV) (n = 20) and in hematologically normal controls (n = 27).
Results: AK2
V617F was detected in 24 of 41 (58.5%) subjects with BCS, 19 of 20 PV controls, and 0 of 27 hematologically normal controls. Mean hemoglobin concentration and hematocrit were significantly higher in patients with
JAK2V617F. Bone marrow was hyperplastic in 16 of 41 subjects (12/16
JAK2V617F positive). Nine of 33 (27.3%) showed endogenous erythroid colony formation (7/9
JAK2V617F positive). Eleven of 41 subjects developed overt MPD (8/11 essential thrombocythemia, 3/11 PV) after the diagnosis of BCS (median, 49 months; range, 8–87 months), and in 90.9% of these
JAK2V617F was detected.
Conclusions: JAK2
V617F occurs in a high proportion of patients with BCS. Latent MPD was missed in a substantial number of our subjects by using standard techniques. Such cases should be screened for
JAK2V617F and carefully observed for the subsequent development of overt MPD.
During the COVID‐19 pandemic, access to health services has been considerably restricted and furthermore, patients have been reluctant to attend for routine monitoring, and this may have had a ...negative impact in the management of patients affected with haematological disorders. Sudden blast crisis in chronic myeloid leukaemia is categorized as a rapid onset of blastic phase, after a documented ‘optimal’ response to tyrosine kinase inhibitor (TKI) therapy and within 3 months of a normal complete blood count. Herein, we describe a case of patient who developed sudden blast crisis after TKI while in treatment‐free remission.
The second decade of this millennium was characterized by a widespread availability of chimeric antigen receptor T-cell (CAR-T) therapies to treat relapsed and refractory lymphomas. As expected, the ...role and indication of allogeneic haematopoietic stem cell transplant (allo-HSCT) in the management of lymphoma changed. Currently, a non-neglectable proportion of patients will be considered candidate for an allo-HSCT, and the debate of which transplant platform should be offered is still active.
to report the outcome of patients affected with relapsed/refractory lymphoma and transplanted following reduced intensity conditioning at King's College Hospital, London, between January 2009 and April 2021.
Conditioning was with 150mg/m2 of fludarabine and melphalan of 140mg/m2. The graft was unmanipulated G-CSF mobilized peripheral blood haematopoietic stem cells (PBSC). Graft-
-host disease (GVHD) prophylaxis consisted of pre-transplant Campath at the total dose of 60 mg in unrelated donors and 30 mg in fully matched sibling donors and ciclosporin.
One-year and five years OS were 87% and 79.9%, respectively, and median OS was not reached. The cumulative incidence of relapse was 16%. The incidence of acute GVHD was 48% (only grade I/II); no cases of grade III/IV were diagnosed. Chronic GVHD occurred in 39% of patients. TRM was 12%, with no cases developed within day 100 and 18 months after the procedure.
The outcomes of heavily pretreated lymphoma patients are favorable, with median OS and survival not reached after a median of 49 months. In conclusion, even if some lymphoma subgroups cannot be treated (yet) with advanced cellular therapies, this study confirms the role of allo-HSCT as a safe and curative strategy.
High dose steroids (HDS) are used in the treatment of haematological malignancies. The reported risk of steroid-induced diabetes (SID) is high. However, screening is not consistently performed. We ...implemented a protocol for detection and management of SID and steroid-induced hyperglycamia (SIH) in haematology outpatients receiving HDS.
Eighty-three people were diagnosed with a lymphoproliferative disorder, of whom 6 had known Type 2 diabetes. Fifty-three people without known diabetes were screened by HbA1c and random venous plasma glucose. All patients (n=34) subsequently prescribed HDS checked capillary blood glucose (CBG) pre-breakfast and pre-evening meal. Treatment algorithms used initiation and/or dose titration of gliclazide or human NPH insulin, aiming for pre-meal CBG 5–11mmol/l. Type 2 diabetes was identified in 4/53 people screened (7.5%). Of 34 people treated with HDS, 17 (44%) developed SIH/SID. All 7 people with Type 2 diabetes developed SIH and 3 required insulin. Of 27 people without known diabetes, 8 (30%) developed SID and 1 required insulin. Pre-treatment HbA1c was higher in people who developed SID compared to those that did not (p=0.002). This is the first report of a SID/SIH detection and treatment protocol for use in people with lymphoproliferative disorders receiving intermittent HDS, demonstrating its feasibility and safety.
Summary
The MATRix chemoimmunotherapy regimen is highly effective in patients with newly diagnosed primary diffuse large B‐cell lymphoma of the central nervous system (PCNSL). However, nothing is ...known about its feasibility and efficacy in everyday practice, where patients are more often older/frailer than those enrolled in clinical trials. We conducted a retrospective study addressing tolerability/efficacy of MATRix in 156 consecutive patients with newly diagnosed PCNSL treated outside a clinical trial. Median age and ECOG Performance Status of considered patients were 62 years (range 28–78) and 2 (range 0–4). The overall response rate after MATRix was 79%. Nine (6%) treatment‐related deaths were recorded. After a median follow‐up of 27.4 months (95% confidence interval CI 24.4–31.9%), the two‐year progression‐free and overall survival were 56% (95% CI 48.4–64.9%) and 64.1% (95% CI 56.7–72.5%) respectively. Patients not eligible for the IELSG32 trial were treated with lower dose intensity and had substantially worse outcomes than those fulfilling inclusion criteria. This is the largest series of PCNSL patients treated with MATRix outside a trial and recapitulates the IELSG32 trial outcomes in the non‐trial setting for patients who fit the trial criteria. These data underscore the feasibility and efficacy of MATRix as induction treatment for fit patients in routine practice.
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