This report outlines the evaluation of physiotherapist-led prehabilitation/rehabilitation for recipients of chimeric antigen receptor T (CAR-T) cell therapy.
A hybrid approach was used, incorporating in-person assessment of quality of life and functional capacity (6-min walk test and timed sit-to-stand test), and a personalised home exercise programme with remotely delivered physiotherapist support pre/post-admission.
Functional deficits were prevalent at referral for CAR-T. Prehabilitation and rehabilitation were highly acceptable to patients, and improvements in functional capacity were documented pre-admission.
This data highlights the importance of pre-CAR-T functional assessment and prehabilitation to optimise preparation and recovery.
Variants of uncertain significance (VUS) are commonly reported in cancer with the widespread adoption of diagnostic massive parallel sequencing. The rate of reclassification of VUS in patients with haematological malignancy is not known and we evaluated this retrospectively. We also investigated whether re-evaluating VUS in 12–24 months or greater than 24 months post-initial classification was significant.
A retrospective audit of patients with haematological malignancies referred to the Molecular Medicine Department at the John Hunter Hospital in Newcastle, Australia between September 2018 and December 2021. Data was analysed for VUS, which was then re-analysed in standard software using current somatic variant guidelines. Proportions of VUS at baseline were compared to post-re-analysis.
The most common diagnoses in the patient cohort (n = 944) were acute myelogenous leukaemia (41%), myelodysplastic syndrome (31%), and chronic myelomonocytic leukaemia (7%). A total of 210 VUS were re-analysed. The most common VUS were in the TET2 (20%), RUNX1 (10%) and DNMT3A (9%) genes. A total of 103 were re-analysed at 24–39 months post-initial classification and 107 variants were re-analysed between 12 and 24 months post-initial classification. Of these, 33 (16%) of VUS were re-classified at 24–39 months and 12 (11%) were re-classified at 12–24 months post-initial classification. The most common variants that were re-classified in both groups were CSF3R (32%), TET2 (29%), ASXL1 (11%) and ZRSR2 (11%).
This study on reclassification of VUS in blood cancers demonstrated that one in seven VUS were re-classified 12 months post initial classification. This can inform practice guidelines and potentially impact the prognosis, diagnosis and treatment of haematological malignancies.
Autoimmune hemolytic anemia (AIHA) is an acquired condition caused by autoantibody mediated destruction of erythrocytes. AIHA is classified as warm or cold depending on whether the autoantibodies involved react optimally at or below body temperature (37°C), respectively. Mixed AIHA, with features of both, is rare and clinically more severe. We report a case of mixed AIHA that was found to be the presentation of systemic lupus erythematosus (SLE). Treatment with rituximab and prednisone resulted in good response. Although more commonly associated with warm AIHA, SLE can present with mixed AIHA.
A 66-year-old woman was being monitored for severe osteoporosis. Laboratory studies showed a 6 g/dL M spike and immunoglobulin M kappa paraprotein. Also, CRAB criteria were met.
The bone marrow (BM) aspirate revealed the presence of 30% atypical plasma cells (PC), which contained numerous large cytoplasmic azurophilic granules that appeared as dots resembling intracellular microorganisms. Concurrently, these cells were reminiscent of the “storage-type” histiocytes reported in lysosomal storage diseases (Figure 1, Panels A and B; May-Grunwald Giemsa stain [MGG], x100 objective). However, a subset of PC displayed coarse azurophilic granules, morphologically consistent with Snapper-Schneid bodies (Figure 1, Panels A and B [arrows]; MGG stain, x100 objective). Flow cytometry of the BM aspirate revealed a monotypic CD38+/CD138+ PC population with an aberrant profile characterized by the loss of CD45 and CD19. These PC were also CD56-, CD200+, CD20+, CD117+, and CD27- (Figure 1, Panel C), and expressed kappa immunoglobulin light chain, consistent with the observed paraprotein.
Various types of cytoplasmic inclusions have been documented in plasma cell neoplasms, including Russell bodies, crystals, and Auer rod-like inclusions, while azurophilic granules and Snapper-Schneid bodies remain uncommon. This myeloma case is particularly noteworthy as it demonstrates the presence of both azurophilic granules and Snapper-Schneid bodies in an untreated patient with a rare paraprotein: immunoglobulin M kappa. Previous case reports have documented this phenomenon in pretreated patients, including those involving diamidine treatment [1].
The presence of PC with atypical granules and an aberrant immunophenotype underscores diagnostic complexity, requiring thorough morphological and immunological examination. Careful distinction of these features from those of microbial infections or lysosomal storage diseases is essential to ensure appropriate clinical management.
Radu Chiriac wrote the manuscript; Lucile Baseggio and Luc-Marie Gerland conducted the cytological and flow cytometric studies. All authors contributed to the final manuscript.
The authors declare no conflict of interest.
The authors received no specific funding for this work.
This manuscript respects the ethical policy of Hospices Civils de Lyon for the treatment of human research participants.
No patient-identifying data were used. The authors did not obtain written informed consent from the patient but the patient did not object to his data being used for research purposes (as required by the ethics policy of Hospices Civils de Lyon).
The authors have confirmed clinical trial registration is not needed for this submission.
Hairy cell leukemia is an uncommon B-cell malignancy with excellent response to purine analogs and to targeted therapies such as ibrutinib and vemurafenib. However, purine analogs are known to be highly immunosuppressive and the infection burden in this patient population with current therapies is unknown. We therefore conducted a retrospective cohort study following 149 patients. Median follow-up time was 6.9 years. Thirty-six percent developed an opportunistic or serious infection requiring hospitalization. Most cases were bacterial and most coincided with neutropenia and/or CD4 T-lymphopenia. No single treatment agent was significantly associated with increased or decreased incidence of infection. Reassuringly, the cumulative incidence of infections plateaued 2 months after initial treatment suggesting clinically significant immune recovery. Only one patient in our cohort passed away due to infection. Estimated 10-year overall survival was 99% suggesting that infections may not cause as much mortality as was seen prior to current therapies.
Voxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin-oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction. We followed four patients for 2–5 months during and/or after voxelotor therapy. This study showed no observable increase in cerebral blood flow or oxygen extraction fraction during treatment.
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