EJHaem最新文献

Multiple myeloma remains an incurable cancer mostly affecting older adults and is characterized by a series of remission inductions and relapses. This study aims to evaluate the outcomes in newly diagnosed transplant-ineligible patients using bortezomib/lenalidomide-based regimens in the Canadian real world as well as their outcomes in the second line. The Canadian Myeloma Research Group Database (CMRG-DB) is a national database with input from multiple Canadian Centres with now up to 8000 patients entered. A total of 1980 transplant ineligible patients were identified in the CMRG-DB between the years of 2007–2021. The four most commonly used induction regimens are bortezomib/melphalan/prednisone (VMP) (23%), cyclophosphamide/bortezomib/dexamethasone (CyBorD) (47%), lenalidomide/dexamethasone (Rd) (24%), and bortezomib/lenalidomide/dexamethasone (VRd) (6%). After a median follow-up of 30.46 months (0.89–168.42), the median progression-free survival (mPFS) and median overall survival (mOS) of each cohort are 23.5, 22.9, 34.0 months, and not reached (NR) and 64.1, 51.1, 61.5 months, and NR respectively. At the time of data cut-off, 1128 patients had gone on to second-line therapy. The mPFS2 based on first-line therapy, VMP, CyBorD, Rd, and VRd is 53.3, 48.4, 62.7 months, and NR respectively. The most common second-line regimens are Rd (47.4%), DRd (12.9%), CyBorD (10.3%), and RVd (8.9%) with a mPFS and a mOS of 17.0, 31.1, 15.4, and 14.0 months and 34.7, NR, 47.6, 33.4 months, respectively. This study represents the real-world outcomes in newly diagnosed transplant-ineligible myeloma patients in Canada. The spectra of therapy presented here reflect the regimens still widely used around the world. While this is sure to change with anti-CD38 monoclonal antibodies now reflecting a new standard of care in frontline therapy, this cohort is reflective of the type of multiple myeloma patient currently experiencing relapse in the real-world setting.

Methotrexate (MTX) doses on days +1, +3, +6, and +11 after match unrelated donor allogeneic stem cell transplant (MUD HSCT) is a common graft-versus-host disease (GVHD) prophylaxis regimen. However, the overlapping toxicity of MTX with conditioning chemotherapy sometimes warrants the omission of the fourth dose of MTX. Prior single-institution studies showed conflicting results comparing the outcomes of patients who received three versus four doses of MTX, but to our knowledge, the effect of concomitant antithymocyte globulin (ATG) has not been reported. Charts of patients who underwent MUD HSCT between 2009 and 2023 were reviewed. Patients received rabbit ATG (Thymoglobulin), given at 0.5 mg/kg on day −3, 2 mg/kg on day −2, and 2.5 mg/kg on day −1. MTX is given at 15 mg/m² on day +1 and 10 mg/m² on days +3, +6, and +11. Severe mucositis was the most common indication for day +11 MTX omission (82%). We identified 292 patients (116 in 3 dose cohort and 176 in 4 dose cohort). Median follow-up was 23 months (range 1–151). Patients in the 4 doses cohort were more frequently male (68% vs. 50%, p < 0.01), received a reduced intensity conditioning regimen (38.0% vs. 22%, p < 0.01), were older (median 58 vs. 54 years, p = 0.02), and received a transplant in the earlier era (median HSCT year 2014 vs. 2018, p < 0.01). A statistically significant difference was not evidenced between the cohorts for the following outcomes: acute GVHD (aGVHD) (HR 1.1, 95% CI 0.9–1.5), chronic GVHD (cGVHD) (HR 1.3, 95% CI 0.8–1.6), relapse-free survival (RFS) (HR 1.0, 95% CI 0.6–1.5), non-relapse mortality (NRM) (HR 1.4, 95% CI 0.9–2.2), and overall survival (OS) (HR 1.2, 95% CI 0.9–1.7). Both cohorts had similar median time to neutrophil engraftment at 14 days. When ATG is incorporated, omission of day +11 MTX does not significantly impact the rate of engraftment or cumulative incidence of aGVHD, cGVHD, RFS, NRM, and OS.

Follicular lymphoma (FL) is a clinically heterogeneous disease. The need for treatment, treatment sequencing, number of treatment lines, and its association with survival have not been described in a population-based setting. We identified all patients diagnosed with FL in the Swedish Lymphoma register from 2007 to 2014, followed until 2020, with detailed data on progression/relapse, transformation, and 2nd and further lines of therapy. During a median follow-up of 6.8 years, 1226 patients (69%) received 1st systemic treatment, 358 patients (20%) were managed with watch-and-wait (WaW) only, and 188 (10%) patients were treated with radiotherapy and did not require additional therapy during the study period. Among patients starting systemic treatment, 496 (40%), 224 (18%), and 88 (7%) received 2nd-, 3rd-, or 4th-line therapy, respectively. The 10-year cause-specific cumulative incidence of transformation was 13%. Among patients managed with 1^st line R-single, R-CHOP, or BR, 54%, 33%, and 29% required 2nd line, respectively. The cumulative probability of starting subsequent treatment within 2 years was 26% after 1st line and 35% after 2nd line treatment. Two-year OS following 1st, 2nd, 3rd, and 4th line systemic treatment was 84%, 70%, 52%, and 36%, respectively, and remained similar when excluding transformations. We conclude that a substantial proportion of FL patients can be managed with WaW for a long period of time, while patients who require multiple treatment lines constitute a group with a large clinical unmet need. These results constitute valuable real-world reference data for FL.

The role of eculizumab in treating Shiga-toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) patients with neurological involvement remains unclear. We describe two distinctly different STEC-HUS patients with neurologic involvement successfully managed with eculizumab, and perform a literature review of all published cases. Both patients had complete resolution of neurological symptoms after initiation of eculizumab. Eighty patients with STEC-HUS treated with eculizumab were identified in the literature, 68.7% had complete resolution of neurological symptoms. Based on our experience and literature review, three prevailing themes were noted: 1) Early eculizumab administration optimized neurological outcomes, 2) Symptom resolution may not be immediate, neurological symptoms may initially worsen before improvement, and 3) Plasma exchange yielded no benefit. Early administration of eculizumab may reverse neurotoxicity in patients with STEC-HUS.

Primary large B-cell lymphomas of immune-privileged sites (IP-LBCLs) comprise LBCLs arising within “immune sanctuaries,” including the central nervous system (CNS), vitreoretina, and testes. Although patients present with localized disease, the prognosis remains poor with high relapse rates, either at the originating site or within another immune-privileged site. Generally, in the presence of an antecedent IP-LBCL, subsequent LBCLs are expected to be clonally related. However, we present a primary CNS LBCL and later primary testicular LBCL in a middle-aged man, diagnosed over a decade apart, which proved to be clonally unrelated by targeted ultra-deep next-generation sequencing of the IgH locus.

A 23-year-old female presented with widespread petechiae and oral mucosal bleeding. There was no palpable lymphadenopathy or hepatosplenomegaly. Complete blood count included haemoglobin 77 g/L (normal 115–155), white cell count 20.4 × 10⁹/L (4.0–12.0), “blasts” 10.6 (52%), neutrophils 3.3 × 10⁹/L (2.0–8.0), platelets 11 × 10⁹/L (150–400). Peripheral blood morphology demonstrated monomorphic immature mononuclear cells with deeply basophilic cytoplasm and numerous small cytoplasmic vacuoles (Figure 1, left image; 1000x magnification) and markedly elevated serum lactate dehydrogenase (14358 IU; 120–250), suggestive of Burkitt leukaemia/lymphoma. Blood was analysed using standard methods as outlined by the ICSH (International Committee for Standardization in Haematology). Immunophenotyping demonstrated CD10+, CD19+ CD20+, CD22+,CD24+, CD34-, CD38+, CD45+ (dim) and CD58+ with cytoplasmic lambda light chain restriction (without surface light chain expression) consistent with a B-cell lymphoma or pre-B ALL. Bone marrow was markedly hypercellular with 83% neoplastic cells with identical morphology (Figure 1, middle image; 1000x magnification). Immunohistochemistry was negative for TdT and CD34. Chromosomal studies identified an unbalanced t(5;8)(q13;p21) resulting in the loss of part of the long arm of chromosome 5, and deletion of 9p by microarray. Fluorescent in-situ hybridisation did not identify MYC rearrangements typical of Burkitt lymphoma. Targeted molecular studies identified NRAS and BRAF variants and whole genome and transcriptome analysis demonstrated a MEF2D::HNRNPUL1 rearrangement (Figure 1, right image). Prior to molecular results being available, the patient was commenced on R-CODOX-M/R-IVAC, achieving complete remission. With full diagnostic information available, consolidation delivered an ALL regimen. This case highlights how, despite a thorough investigation by all appropriate modalities including morphology, immunophenotyping and cytogenetics, the final correct diagnosis may be delayed until the determination of the molecular profile. Further complicating this case, B-ALL with MEF2D has only recently been described under the category of B-lymphoblastic leukaemia/lymphoma with other defined genetic abnormalities (WHO, 2022).

The authors declare no conflict of interest.

Patient has moved overseas so consent is not feasible. Patient's details areadequately anonymised.

N/A

All patient treatment protocols in our institution are agreed to by the Institutional Ethics Committee.

A distinct subset of acute myeloid leukemia (AML) is characterized by the presence of the Philadelphia chromosome (Ph+), due to reciprocal translocation t(9;22)(q34;q11.2). This chromosomal rearrangement leads to the fusion of the breakpoint cluster region (BCR) gene on chromosome 22 with the ABL1 gene on chromosome 9, generating the BCR::ABL1 fusion gene. The Ph+ AML subtype is associated with poor prognosis and resistance to conventional chemotherapy. Beyond the well-established BCR::ABL1 fusion, recent studies have shed light on additional genetic abnormalities in Ph+ AML, including associations with rearrangements involving core binding factor beta (CBFB). We describe a case of de novo AML with concurrent BCR::ABL1 and CBFB::MYH11 rearrangements.

Talquetamab recently received approval for relapsed refractory multiple myeloma. However, there is currently no available data on how patients perform with BCMA based agents after progression on talquetamab. Herein, we present the outcome of 10 patients who received BCMA based therapies following talquetamab. The median follow-up was 9.5 months (range: 6–24 months). The median progression free survival was 5.5 months (range: 1–10 months). Patients had varying grades of cytokine release syndrome and Immune effector cell-associated neurotoxicity syndrome. Our results suggest that treatment with talquetamab followed by BCMA based therapies is feasible and can be considered as clinically indicated.

A 70-year-old woman presented with slowly progressive loss of vision in both eyes over the course of 1.5 years. Ophthalmologic examination revealed multiple bilateral crystal-like granular deposits in the cornea (Figure 1A), predominantly in the anterior stroma as well as in the conjunctiva of the right eye. In addition, prominent corneal nerves were observed bilaterally, caused by deposits along these nerves (Figure 1B).

Amyloid was identified in a conjunctival biopsy by Congo red staining in combination with polarization microscopy (red-stained deposits on light-microscopy [Figure 1C; original magnification 50×]). Immunofluorescence staining showed that these deposits contained lambda light chains (Figure 1D; original magnification 200×) and were negative for kappa light chain or IgG. A diagnosis of corneal amyloid light-chain (AL) amyloidosis was established.

Workup for AL amyloidosis included bone marrow analysis, which revealed the presence of 10% plasma cells. Laboratory findings included an IgG-lambda M-protein of 17 g/L with a moderate increase of lambda light-chain level (lambda light chain: 63 mg/L; kappa light chain: 13 mg/L). Cytogenetic analysis of purified plasma cells revealed the presence of t(14;16) and gain1q21. Additional staging showed evidence of asymptomatic renal (proteinuria) and cardiac amyloidosis (typical MRI findings; Mayo 2004 stage II). There was no myeloma-related organ damage (no acronym for hypercalcemia, renal failure, anemia, and bone disease (CRAB) manifestations). Therapy with bortezomib-dexamethasone was initiated to eradicate the plasma cell clone, which is responsible for the production of toxic light chains, and 3 months later she achieved a complete hematologic response, which persists until now (2.5 years after starting therapy). Her visual impairment no longer deteriorated, and her proteinuria disappeared over time.

Corneal involvement is extremely rare in systemic AL amyloidosis and can lead to loss of visual acuity if not properly treated. In addition, it is noteworthy that, in this case, the ocular findings resulted in the eventual diagnosis of AL amyloidosis, before the development of advanced cardiac disease, which carries a very poor prognosis. The development of ocular pathology in our patient is probably related to specific physicochemical properties of the monoclonal lambda light chains produced by the clonal bone marrow-localized plasma cells.

N.v.d.D and M.D. treated the patient; C.H. performed the pathology evaluations; N.v.d.D. wrote the first version of the manuscript; M.D. and C.H. critically reviewed the manuscript.

N.W.C.J.v.d.D. has received research support from Janssen Pharmaceuticals, AMGEN, Celgene, Novartis, Cellectis, and BMS and serves on advisory boards for Janssen Pharmaceuticals, AMGEN, Celgene, BMS, Takeda, Roche, Novartis, Bayer, Adaptive, Pfizer, Abbvie, and Servier, all paid to the institution. C.H. and M.D. declare no conflicts of