Annals of Hematology最新文献

Pregnant women with paroxysmal nocturnal hemoglobinuria (PNH) are at high risk for life-threatening thromboembolism. Therapy with the complement inhibitor eculizumab is able to mitigate thrombotic risks in PNH and to improve pregnancy outcomes. However, whether PNH with low-level hemolysis in pregnancy can be safely managed without complement inhibition is unclear.Here, we describe two pregnant patients with PNH in the setting of bone marrow failure and low-level hemolysis with lactate dehydrogenase (LDH) < 1.5 x upper limit of normal [ULN]. In both patients, management consisted solely of prophylactic anticoagulation, without the use of complement inhibition. Both pregnancies ended successfully without thromboembolic complications.We conclude that in pregnant patients with PNH and low-level hemolysis (i.e. LDH < 1.5 x ULN), management with close monitoring and prophylactic anticoagulation only, without use of complement inhibition, might be a reasonable strategy. More data to guide optimal management of pregnant women with PNH are needed.

Haematologic malignancies are considered among the more common adolescent and young adult (AYA) cancers. Many female AYA patients with haematopoietic malignancies face impaired fertility. Haematologic malignancies patients tend to be treated with more aggressive systemic chemotherapy than that of solid tumours. In adult women, treatment-related contraception causes age-related fertility loss. Graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation is associated with decreased fertility. Ovarian cryopreservation is often indicated for haematopoietic malignancies; however, follicle loss associated with ovarian cryopreservation and ovarian minimal residual disease, which result in the withdrawal of the transplantation, are important issues. These problems may not be fully addressed by conventional methods of fertility preservation, such as oocyte, embryo, and ovarian cryopreservation, leaving room for research into new treatment approaches, such as fertility preservation drugs. In recent years, preclinical studies have shown that mTOR inhibitors may preserve chemotherapy-induced follicular loss, may have follicle-preserving effects on follicle loss associated with cryopreservation and transplantation of ovarian tissue, may have fertility-preserving effects on aging-related infertility. Clinical studies have shown that mTOR inhibitors may have the potential for indirect fertility preservation by controlling GVHD, have a limited anti-tumor effect against haematopoietic malignancies. The purpose of this article is to outline the various issues faced by female survivors of haematopoietic malignancies and discuss the potential of mTOR inhibitors as a safe treatment option. Based on current research, mTOR inhibitors seem promising and innovative fertility preservation agents regarding preclinical conditions, and further study, including clinical trials, should be expected.

Acute leukemia with TCF3::ZNF384 is a distinct type of acute leukemia that present most commonly as B-acute lymphoblastic leukemia or mixed-phenotype acute leukemia (B/myeloid). We report the first case of TCF3::ZNF384 mixed-phenotype leukemia presenting as isolated extramedullary disease in the mediastinum. Diagnosis using RNA-sequencing and whole genome sequencing on the primary issue is illustrated.

Daratumumab and bortezomib, the first-line drugs for AL amyloidosis, typically yield a complete hematologic response (CHR) rate of nearly 60% when used in combinations. An early achievement of CHR is crucial in amyloidosis. We retrospectively evaluated the relationship between dFLC (the difference between free light chain) reduction by Day 7 in Cycle 1 (C1D7) and CHR, organ response, and survival in 48 newly diagnosed AL amyloidosis patients receiving daratumumab, bortezomib, and dexamethasone. The CHR rate within six months was 66.7%. Using Receiver Operating Characteristic Curve curve analysis, we predicted CHR based on a dFLC reduction in C1D7 (67.0% change, optimal sensitivity 87.5%, specificity 81.3%). We introduce the novel concept of "rapid hematologic dFLC response", defined as a reduction in dFLC levels ≥ 67% in C1D7. The CHR rate in rapid responders' groups was higher than that in slow responders' group (90.3% vs. 23.5%, P<0.01). After a median follow-up of 19 months (range: 0.3-57), the renal response rate in rapid responders was higher than that in slow responders (72.0% vs. 27.5%, P = 0.025). The median major organ deterioration event-free survival in the rapid responders' group (not reached) was significantly superior to that in the slow responders' group (19 m, 95% CI: 1.79-23.14 m, P = 0.048). In conclusion, early dFLC reduction in C1D7 indicates a high possibility of CHR and organ response and may allow for early modification of therapy in selected patients.

To synthesize the evidence on the efficacy and safety of teclistamab in treating relapsed/refractory multiple myeloma (RRMM). A systematic search for records published from inception until June 2024 was conducted on PubMed, Web of Science, EMBASE, and Google Scholar databases. Five studies with 661 RRMM patients were included in the analysis. The pooled results showed that teclistamab led to an overall response rate (ORR) of 62.8% (95% Confidence Interval (CI): 58.6-66.8), a ≥ very good partial response or better (VGPR) of 52.1% (95% CI: 46.8-57.3), and a ≥ complete response or better (CR) of 29.5% (95% CI: 21.9-38.4). When the ORR was assessed in different subgroups, we found that patients with extramedullary disease (EMD) had considerably lower ORR than those without EMD (45% vs. 71%, p < 0.0001). The ORR was significantly lower in patients with prior (B-cell maturation antigen) BCMA-directed therapy (OR: 2.24, p = 0.002) and those with stage III disease (OR: 3.69, p = 0.0001). However, the subgroup analyses showed no considerable difference in the ORR between patients with high or standard-risk cytogenetics (OR: 1.05 p = 0.82) and those with penta-drug or triple-class-refractory disease (OR: 0.97 p = 0.89). Regarding the safety of teclistamab, the pooled results showed that the incidence of grade ≥ 3 adverse events was high (90.7%). However, grade ≥ 3 cytokine release syndrome (CRS) and neurotoxic events were low (1.5% and 2.2%, respectively). RRMM patients treated with teclistamab display good response rates.

The immune system of chronic myeloid leukemia (CML) patients is severely impaired, hampering anti-tumor responses, and maximal immune recovery occurs after achieving deep molecular responses to tyrosine kinase inhibitors. This study aimed to discern the expression patterns of NCR2, IL2, IL4, EOMES, FOXP3, GATA3, RORGT, PD1/PDL1 and TIM3/GAL9, expanding our previous dataset up to 19 key immune mediators, during the initial year on imatinib. Gene expression dynamics were evaluated in 171 peripheral blood samples from 89 CML patients, including 43 longitudinally monitored individuals, and 52 healthy donors. Univariate and unsupervised analyses confirmed diminished expression of most studied immune mediators, except for TNF, ARG1 and IL4, differentiating between baseline and 3-month samples. Most of the studied mediators normalized along treatment, with a transient increase of TNF and IL6 levels at 3-months, especially in optimal responders (BCR::ABL1 < 0.1%). Univariate and multivariate analyses showed heightened ARG1 levels and a transition from PD1/PDL1 dominance at 3 months to TIM3/GAL9 at 12 months in non-optimal responders (BCR::ABL1 ≥ 0.1%). Our longitudinal design offers a deeper exploration of immune gene expression dynamics in CML patients on imatinib, highlighting its potential implications for therapy outcomes.

Lactate dehydrogenase (LDHA) activation induces tumorigenesis by activating tumor proliferation, growth, invasion, and metastasis. Whether LDHA mediates tumor metabolism that upon diffuse large B-cell lymphoma (DLBCL) occur remains unknown. Here, we investigated how LDHA adopt tumor metabolism after activation to regulate DLBCL-inducible. We investigated LDHA is highly expressed in peripheral blood mononuclear cells (PBMCs) of DLBCL patients. Knockdown of LDHA results in an increase in the apoptosis of cells, suppression of cell growth and migration in OCI-Ly1 and OCI-Ly10 cells. We show that LDHA gains a canonical enzyme activity to produce lactate and triggers NAD + in DLBCL cells. Furthermore, p-STAT5 was identified as a downstream target of LDHA, and the p-STAT5 protein level was significantly reduced related to decreased LDHA protein expression. Collectively, our findings identify the oncogenic role of LDHA in DLBCL and suggest that LDHA can be considered as a pivotal prognostic biomarker and a potential therapeutic target.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for myelodysplastic syndrome (MDS). However, relapse remains the primary cause of transplantation failure. This single-center study aimed to evaluate factors influencing therapeutic interventions to prevent overt relapse of MDS and to identify treatment approaches that ensure optimal response and safety. We enrolled 149 patients with relapsed MDS who had undergone allo-HSCT between May 2009 and December 2017, among whom 87 patients had hematologic relapse (HemRel; marrow blasts ≥ 5%, blasts in peripheral blood or dysplasia fulfilling MDS diagnostic criteria) and 62 patients had pre-HemRel; pre-HemRel included imminent (n = 28; donor chimerism ≤ 95%), WT1-based molecular (n = 17; WT1 transcript > 250 copies/10⁴ABL1), and cytogenetic (n = 17; recurrence of chromosomal aberrations) relapses. The estimated 4-year overall survival (OS) rate from the time of relapse was 44.1% among 62 pre-HemRel patients. However, the OS rate was significantly lower in 87 HemRel patients. In a multivariate analysis, preemptive use of cellular immunotherapy (cIMTx, either donor lymphocyte infusion, second allo-HSCT, or both) emerged as an independent factor in preventing HemRel and was more effective, particularly in the presence of other unfavorable factors, such as the absence of chronic graft-versus-host disease and a higher-risk group based on the MDS-transplantation prognostic scoring system. In HemRel, using cIMTx demonstrated a significantly superior OS rate compared to non-cIMTx modalities (25.8% vs. 6.1% vs. 0%, P < .001). In summary, cIMTx demonstrated superior outcomes in both pre-HemRel and HemRel groups, proving particularly advantageous in pre-HemRel cases with progression risk factors, while its benefits remained consistent in HemRel cases.