EJHaem最新文献

Platelet satellitism refers to the rosetting of the platelets around white blood cells, mostly neutrophils that could lead to spuriously low platelet counts on automated analyzers. The phenomenon has usually been described in EDTA processed blood samples. We describe the clinical course of a patient with immune thrombocytopenia with platelet satellitism in both EDTA as well as non EDTA processed blood samples. We also review the literature describing two other reports of the platelet satellitism in patients with immune thrombocytopenia. We also reference the literature describing the heterogeneity of the presence of platelet satellitism in different clinical and laboratory settings.

CD7 targeted CAR-T has demonstrated potential in the treatment of T cell malignancies but no study has been reported about its potential in the prophylaxis of GVHD in allo-HSCT. Here we reported a special case that a boy diagnosed with refractory acute T lymphoblastic leukemia (T-ALL) was treated with universal CD7 targeted CAR-T (CD7 UCAR-T) and parent-derived peripheral blood stem cells (PBSCs). Complete remission and full engraftment of donor was observed. In the later four months of follow-up, in the absence of any immunodepression treatment, no signs of GVHD were observed. This case initially demonstrates the potential of CD7 UCAR-T in the prophylaxis of GVHD.

The PICALM::MLLT10 fusion gene is a rare but recurrent event in acute leukemia (AL) associated with poor prognosis. It is still confused whether PICALM::MLLT10 can solely correspond to acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or acute leukemias of ambiguous lineage (ALAL). Here, we reported a series of PICALM::MLLT10 positive AL patients with miscellaneous immunophenotype including T-ALL, ALAL, AML, and B-ALL, complex karyotype, half of extramedullary disease (EMD), frequently concomitant PHF6 mutation, and poor initial treatment response to standard chemotherapy aiming to different immunophenotype, but showing sensitivity to combining chemotherapy especially integrated with venetoclax, suggesting this fusion gene may indicate a new subgroup of AL. Eighteen PICALM::MLLT10 positive patients of 533 AL patients (18/533, 3.4%) were identified by RNA sequencing in our center. We found PICALM::MLLT10 positive AL showing miscellaneous immunophenotype, higher expression of leukemic stemness genes and lower expression of biomarkers of venetoclax resistance, more extramedullary involvement, and especially poor response to conventional induction chemotherapy, but may benefit from venetoclax as well as low-dose Ara-C, granulocyte colony-stimulating factor (G-CSF), and anthracyclines combination chemotherapy. Sequential hematopoietic stem cell transplantation (HSCT) after chemotherapy combined with venetoclax may further improve long-term survival in AL patients with complete remission (CR) even measurable residual disease (MRD) positive.

This case report presents the successful management of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia in a 54-year-old male post-allogeneic hematopoietic cell transplantation. The combinatorial approach of sequential antibody treatment (Inotuzumab [InO] and Blinatumomab [Blina]) combined with three donor lymphocyte infusions (DLI) applications and cytoreductive chemotherapy-induced sustained complete molecular remission as documented at the last follow-up 30 months later. This case highlights the feasibility and potential synergistic efficacy of a Blina/DLI regimen and supports the hypothesis that T-cell engagers could enhance the DLI effect. Furthermore, the co-administration of InO, Blina, DLI, and cytoreductive chemotherapy was proven to be feasible without severe adverse events.

Relapse remains a major cause of treatment failure following allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We retrospectively investigated low-dose decitabine and venetoclax (DEC/VEN) as post-transplant maintenance in 26 older patients with AML and MDS. The cumulative incidence of day 100 gIII-IV acute graft versus host disease (GVHD) and 1-year moderate-severe chronic GVHD was 5% and 26%, respectively. One patient relapsed 14 m after transplant. The 1-year non-relapse mortality and survival were 11% and 84%, respectively. DEC/VEN is a safe and potentially effective strategy to reduce the risk of post-transplant relapse.

A 35-year-old man presented with dizziness, exertional dyspnea, and palpitations for 1 month without fever. Complete blood count showed anemia (hemoglobin, 40 g/L), leucopenia (3.70 × 10⁹/L), and neutropenia (1.60 × 10⁹/L) with occasional circulating blasts on the peripheral blood smear. Bone marrow aspirate (May-Grünwald-Giemsa stain, ×1000; Figure 1, upper panels) showed 91% medium-sized blasts with around half of them showing “cup-like” nuclei (black arrowheads) and around a third of them showing cytoplasmic and/or nuclear blebs (black arrows). Some of the blasts showed both features (white arrows). Some leukemic cytoplasmic fragments were noted in the background (white arrowheads). Flow cytometry showed B-lymphoblasts which demonstrate co-expression of CD2 and CD371 (Figure 1, lower panel). Karyotype was normal. Next-generation sequencing showed IKZF1 partial deletion (exons 4–7), PTPN11, and multiple NRAS mutations. Targeted RNA sequencing showed the presence of IGH::DUX4 fusion, confirming the diagnosis. The patient was given pediatric-inspired intensive chemotherapy and achieved complete remission. He was planned to have allogeneic hematopoietic stem cell transplantation.

B-lymphoblastic leukemia/lymphoma (B-ALL) with DUX4 rearrangement is a new provisional entity in the 5th edition of the World Health Organization Classification of Hematolymphoid Tumors which is more common in children, adolescents, and young adults and is associated with good prognosis. DUX4 rearrangements in B-ALL are usually cytogenetically cryptic. Co-expression of CD2 and CD371 in B-ALL is strongly associated with DUX4 rearrangement. Yet, morphological description of this entity is scarce. “Cup-like” nuclei in blasts are known to be associated with acute myeloid leukemia with NPM1 and/or FLT3-ITD mutations but are less recognized in B-ALL. Moreover, cytoplasmic and nuclear blebs are hitherto not described as distinctive features in any specific subtype of B-ALL. Further study on the link between the morphological and molecular features of B-ALL with DUX4 rearrangement cases would be of value.

Wing Kit Lam analyzed the data, wrote the paper, and produced the figures. Ching Ching Alice Wong analyzed the data and wrote the paper.

The authors declare no conflict of interest.

No funding source was declared.

The authors have confirmed ethical approval statement is not needed for this submission.

Written informed consent from the patient was obtained.

The authors have confirmed clinical trial registration is not needed for this submission.

In cases of unexplained neutrophilia, granulocyte-colony stimulating factor (G-CSF)-producing tumours should be considered. Although such tumours are mainly reported in solid cancers, a few cases of G-CSF-producing multiple myeloma (MM) have recently been reported [1-4]. Severe neutrophilia raises the possibility of chronic neutrophilic leukaemia (CNL), and the detection of a colony-stimulating factor 3 receptor (CSF3R) mutation is useful in diagnosing CNL [5]. While an association between CNL and plasma cell dyscrasia has been reported [6], a recent study found that plasma cell dyscrasia-derived G-CSF could induce CNL-like neutrophilia without a CSF3R mutation [4], suggesting that when clinicians diagnose CNL in a patient with plasma cell dyscrasia, caution should be exercised to avoid misdiagnosis. Although bone marrow (BM) fibrosis (BMF) is frequently observed in myeloproliferative neoplasms (MPNs), MM with BMF has also been reported [7, 8]. However, the number of MM cases with both neutrophilia and BMF is limited; [1, 9] as such, the clinical characteristics and treatment responses remain unclear. Here, we report the second case of G-CSF-producing MM complicated with paraneoplastic BMF during disease progression; to our knowledge, there is only one other report of this condition to date [1].

A 63-year-old man was admitted to our hospital for evaluation of leucocytosis. His medical history included chronic obstructive pulmonary disease. Blood tests showed that his white blood cell (WBC) count was 19,710 /µL (neutrophils, 85.5%) without anaemia, hypercalcaemia (calcium level, 9.3 mg/dL), renal impairment (blood urine nitrogen level, 11 mg/dL; creatinine level, 0.61 mg/dL), or detectable BCR::ABL1 transcript. BM examination revealed hypercellular marrow with increased immature myeloid cells (Figure 1A), but no increased blasts or BMF (Figure 1B). Thus, a tentative diagnosis of CNL was established, and the patient was followed without treatment. Two years later, he was admitted to the nephrology department after exhibiting elevated urinary protein levels at a health checkup. Blood tests showed a WBC count of 36,100 /µL (neutrophils, 87.8%), haemoglobin level of 12.6 g/dL, and platelet count of 18.8×10⁴/µL. Immunofixation electrophoresis detected κ-type Bence–Jones protein and the serum free light chain ratio (rFLC) was increased by 122. BM examination revealed a hypercellular marrow and an increase in CD138-positive plasma cells to 20% (Figure 1C), although no significant BMF was observed (Figure 1D). Based on these results, the patient was diagnosed with κ-type Bence–Jones protein-type MM. Because he could not afford the treatment and chose to wait without treatment. Four years after MM's diagnosis, his condition worsened, with a neutrophil count of 39,400 /µL, a haemoglobin level of 10.4 g/dL, and a platelet count

Bleeding and thrombosis are common complications during immune thrombocytopenic purpura (ITP) treatment. There is a strong need to predict bleeding and thrombosis risks before ITP treatment to optimize therapy and appropriately manage these complications. We performed a retrospective cohort study of 120 patients with primary ITP to identify a biomarker to predict bleeding and thrombosis. We compared blood test results at diagnosis between patients with and without bleeding or thrombosis episodes. The standard deviation of red blood cell distribution width (RDW-SD) differed significantly between those with and without bleeding and between those with and without thrombosis, leading us to identify it as a variable representative of risk. RDW-SD was significantly associated with patient age and with histories of several vascular diseases. Multivariate regression analyses showed that RDW integrated several variables associated with vascular risks. RDW-SD was significantly associated with difficulty with corticosteroid discontinuation (hazard ratio [HR], 2.22, p = 0.01), incidence of bleeding (HR, 2.75, p< 0.01), incidence of thrombosis (HR, 2.67, p< 0.01) and incidence of infection (HR, 1.78, p = 0.04). The RDW-SD value at the time of ITP diagnosis is a useful biomarker to predict the risks of bleeding, thrombosis, and other complications.

Belantamab mafodotin is the first-in-class antibody-drug conjugates targeting B-cell maturation antigen to have demonstrated effectiveness in triple-class refractory multiple myeloma (TCR-MM) patients. We performed a retrospective study including 78 TCR patients, with at least four prior lines of therapy (LOTs), who received belantamab mafodotin within named patient program and expanded access program in Italy between 2020 and 2022. Median age was 65 years (range 42–86 years), ECOG performance status was ≥1 in 45% of patients. Overall, a clinical benefit was obtained in 36 out of 74 evaluable patients (49%), with 43%, 28%, and 13.5% achieving at least partial response, very good partial response, and complete response, respectively. After a median follow-up of 12 months (range 6–21 months), median duration of response, progression-free survival (PFS), and overall survival (OS) were 14, 5.5, and 12 months, respectively. Age >70 years, good performance status and response were associated with longer PFS and OS. Keratopathy occurred in 58% of patients (G3 2.5%), corneal symptoms in 32% (G3 1.2%) and a reduction in visual acuity in 14%. Grade 3 thrombocytopenia occurred in 9% of patients. Only 3% of patients discontinued belantamab mafodotin because of side effects. This real-life study demonstrated significant and durable responses of belantamab in TCR-MM patients with four prior LOTs, otherwise ineligible for novel immunotherapies.

A 34-year-old woman received umbilical cord blood transplantation for refractory T-cell prolymphocytic leukemia after salvage therapy with alemtuzumab. She developed right angular cheilitis on the 46th day after transplantation, which worsened after receiving systemic steroid therapy for extensive chronic graft versus host disease. The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV-resistant mutations of the herpes simplex virus type 1 (HSV-1) in the thymidine kinase domain. Foscarnet is expected to be effective against ACV-resistant HSV-1 infection. However, it could not be used because the patient developed renal dysfunction. Several viral thymidine kinase mutations related to ACV resistance were found in the patient's sample. Nevertheless, amenamevir, a helicase-primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ACV-resistant HSV infection after allo-HSCT is an rare but important complication in the era of low-dose long-term ACV prophylaxis. To date, there is no established treatment against ACV-resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV-resistant HSV infection in patients with renal failure after allo-HSCT.