Acta Haematologica最新文献

Background: Cardiovascular (CV) adverse events (AEs), especially atrial fibrillation (AF) and hypertension, have been reported in patients receiving treatments for chronic lymphocytic leukemia (CLL), including Bruton's tyrosine kinase inhibitors (BTKis). Although these AEs are managed effectively in most cases and AE management guidelines exist, practical management approaches are inconsistent across regions and practices. We aimed to address these inconsistencies by developing consensus recommendations.

Summary: A European expert panel was assembled comprising eight hematologists and six cardiologists. Literature analysis, expert interviews, and the Delphi method were used to gain consensus on screening, monitoring, and treatment of AF and hypertension statements.

Key messages: Maintaining BTKi treatment is paramount to maximize time to next treatment; for patients at high risk of progression, this can be achieved by appropriately treating hypertension and AF and adjusting the BTKi dose. Patients should be risk-stratified as low, moderate, high, or very-high risk of cancer therapy-related CV toxicity and treated according to their disease status so that CLL treatment can be maintained. Patient education on symptom monitoring, home blood pressure monitoring, and electrocardiograms (baseline, every 3 months) are recommended to detect/monitor AF and hypertension. Close collaboration between hematologists and cardiologists is vital to achieve optimal patient outcomes.

Introduction: This study investigated the efficacy and survival of pediatric refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL) treated with a venetoclax (VEN)-based regimen.

Methods: Children with R/R ALL treated with a VEN-based regimen at Peking University People's Hospital from December 1, 2018, to January 15, 2024, were included in this study. Complete remission (CR) or complete remission with incomplete recovery of blood count (CRi) rates and objective response rates (ORRs) were analyzed.

Results: Twenty-two children with R/R ALL were included in this study. The median duration of VEN treatment per cycle was 21 (7-28) days, and the median VEN dose was 100 (50-300) mg/day. Following a cycle of VEN-based therapy, 17 children (77.3%) achieved CR/CRi/morphological leukemia-free state (MLFS), including 8 cases (8/17) with negative MRD. The ORR in the children with B-cell acute lymphoblastic leukemia (B-ALL) (n = 9) and T-cell acute lymphoblastic leukemia (T-ALL) (n = 8) was 75% and 80%, respectively. Patients with early T-cell precursor (ETP) ALL (n = 6) achieved MRD-negative remission, and one KMT2A::USP2-positive child achieved MLFS after receiving a VEN-based regimen. For the relapsed patients, the median overall survival (OS) was 1,371 days. For the refractory patients, the median OS was unreached. For T-ALL patients, the median OS was 1,371 days. For the patients with B-ALL, the median OS was 543 days. All patients had hematologic adverse reactions within an acceptable range.

Conclusion: Children with R/R ALL who received the VEN-based regimen achieved a high remission rate with an acceptable safety profile. Significantly, the VEN-based regimen was effective in patients with R/R ETP with MRD-negative results while also proving beneficial for KMT2A-rearranged, highlighting VEN-chemotherapy as a treatment option for remission.

Introduction: Myeloid/lymphoid neoplasms with fibroblast growth factor receptor 1 rearrangement (MLN-FGFR1) are rare, heterogenous, aggressive hematologic malignancies with FGFR1 rearrangements at the 8p11 locus. Pemigatinib, a potent selective inhibitor of FGFR1-3, is approved for relapsed/refractory MLN-FGFR1.

Methods: This retrospective chart review included US adults with myeloproliferative neoplasm, unclassifiable (MPN-U), myelodysplastic syndrome (MDS)/MPN, post-MPN acute myelogenous leukemia, precursor T- or B-cell acute lymphoblastic leukemia/lymphoma, or mixed-phenotype acute leukemia with bone marrow biopsy and standard cytogenetic and/or molecular results. Probable cases of MLN-FGFR1 were identified and confirmed with cytogenetic or molecular testing results. Patient characteristics, diagnostic testing methods, treatments, and outcomes were abstracted.

Results: Of 560 submitted cases, 51 (9.1%) were probable MLN-FGFR1, 33 (5.9%) of which were subsequently confirmed. Among patients with confirmed MLN-FGFR1, 8p11 translocation or FGFR1 rearrangements were detected with standard cytogenetics in 72.7%, break-apart fluorescence in situ hybridization in 66.7%, next-generation sequencing in 21.2%, and real-time polymerase chain reaction in 6.1%. All but 1 patient initiated treatment; 3 patients underwent allogenic stem-cell transplant.

Conclusion: This study highlights the importance of cytogenetic and molecular evaluations in patients with chronic/blast phase hematologic malignancies to diagnose MLN-FGFR1. This is particularly important following US approval of pemigatinib for this hematologic malignancy.

Introduction: Pure red cell aplasia (PRCA), autoimmune hemolytic anemia (AIHA), and aplastic anemia (AA) are immune-mediated diseases that affect mainly erythrocytes or erythroid progenitor cells. This study aimed to investigate changes related to autoimmunity in B-cell receptor (BCR) and T-cell receptor (TCR) repertoires in patients with these diseases.

Methods: Patients with primary PRCA, AIHA, and AA and normal controls (NCs) were recruited. Peripheral blood was collected, and BCR and TCR repertoires were sequenced by next-generation immunosequencing.

Results: Ten patients with PRCA, 10 with AIHA, 10 with AA, and 7 NCs were ultimately enrolled. According to the broad repertoire metric analysis, only the TCR repertoire of the AA group was more diverse than that of the NC group (p < 0.05). Regarding BCR and TCR repertoires, the PRCA, AIHA, and AA groups had uniform gene characteristics. The preferential gene of immunoglobulin heavy chains in PRCA patients was correlated with memory cell and red blood cell antigen recognition; genes expressed in the AIHA group were associated with the secretion of autoantibodies, whereas AA patients had more genes related to neutralizing antibodies. For T-cell receptor β (TRB) chains, PRCA patients had skewed use of genes associated with T-cell dysregulation and hyperinflammation, whereas AIHA and AA patients had similar genes as patients with other autoimmune diseases, which correlated with abnormal antigen recognition. PRCA and AA patients had specific TRBV-J gene combinations. For the BCR light chains, PRCA and AIHA patients tended to use more κ chains, whereas AA patients tended to use more λ chains. Regarding the TCRα chains, patients with each of the three diseases expressed more genes related to hypersensitivity reactions (p < 0.05). Compared to the NC group, the PRCA and AIHA groups had greater BCR somatic hypermutation (SHM). The length of CDR3 was similar, but the hydrophobicity differed among the different disease groups. Different motifs were found in BCRs and TCRs of the three diseases. Compared to NCs, the PRCA, AIHA, and AA groups showed a considerable lack of physiological T-cell clusters, and some disease-specific T-cell clusters were found in each disease group.

Conclusion: PRCA, AIHA, and AA patients had different BCR and TCR repertoire characteristics in terms of genes and gene combinations, hydrophobicity and CDR3 motifs, and T-cell clustering, which might contribute to autoimmune antigen recognition. The abnormalities were mainly T-cell related for PRCA patients, B-cell related for AIHA patients and both for AA patients.

Introduction: Multiple myeloma is an incurable chronic malignant disease. The disease itself and its treatment impair quality-of-life (QoL), yet there is no data regarding the biopsychosocial needs of patients in the era of new treatments. In the current study, we aimed to identify the biopsychosocial needs of patients with multiple myeloma.

Methods: This is a descriptive study on patients with multiple myeloma in Israel in 2024. The information was based on a questionnaire examining physical, psychological, and social needs filled out by myeloma patients. We analyzed the main impairments of QoL and what affected them, the main supporter in dealing with the disease, psychosocial needs reported by the patients and the difficulties in dealing with such difficulties.

Results: The main symptom reported by multiple myeloma patients was fatigue. The number of treatment lines worsened QoL (unstandardized coefficient: 0.987, 95% CI: 0.284; 1.691, p = 0.006). The patient's partner mostly helped in dealing with the disease (72.7%). The most desired type of support was assistance in accessing rights (median 5, interquartile range 3-5); however, one-third did not use the support services offered to them. A total of 48% the patients talked to their doctor about the struggle and the accompanying difficulties.

Conclusion: Myeloma patients report various impairments in the biopsychosocial components of QoL. Although supportive services are offered, adjustments must be made to optimally meet patients' needs. Further studies should test the effectiveness of different interventions on the biopsychosocial components of the QoL of these patients in the era of new drugs.

Introduction: Ring chromosomes (RCs) are acquired circular structural abnormalities associated with gain or loss of genetic material, which are thought to be associated with inferior outcomes in patients with myeloid neoplasms (MNs). Responses of patients with MN and RC to the standard therapeutic options have not been previously reported.

Methods: We analyzed the demographics and outcomes of 31 consecutive patients with an MN and RC, comparing overall survival (OS) and progression-free survival (PFS) of patients who received supportive care (n = 9), cytotoxic chemotherapeutic options (n = 3), hypomethylating agents (HMA) alone (n = 6), or HMA in combination with venetoclax (n = 13).

Results: Over 60% of all patients with RC had either a TP53 mutation, loss of 17p, or both. Interestingly, 22/31 (71%) of patients had not received prior radiation or chemotherapy. Patients who received supportive care had a shorter OS (p = 0.001), but none of the therapeutic interventions were associated with further improvement in prolonging OS (p = 0.86) or PFS. The presence of a complex karyotype, TP53 mutations/loss of TP53, or a treatment-related MN was not independently associated with an inferior OS in MN patients with RCs.

Conclusion: These findings indicate that patients with MN and RC have especially poor outcomes and that effective treatment strategies remain an unmet need.

Introduction: Excisional biopsy (EB) is the gold standard for large B-cell lymphomas (LBCLs) diagnosis. Based on recent advances in interventional radiology enabling accurate sampling with core needle biopsy (CNB), we evaluated efficacy and safety of CNB under imaging guidance for diagnosing LBCLs.

Methods: At the Hematology and Pathology Units of the Federico II University Medical School of Naples (Italy), we retrospectively collected patients with lymphadenopathies suspected of lymphomas (during 2009-2022) of which the ultrasonography (US)-guided CNB lymph node samples were available. Subsequently, we investigated the accuracy and safety of US-guided CNB for LBCLs diagnosis.

Results: Over a 12-year period, 800 (superficial target, n = 560; deep-seated target, n = 240) lymph node biopsies performed with 16-gauge diameter modified Menghini needle under power-Doppler ultrasonographic guidance have been evaluated in 800 patients. According to the reference standard, 220 were suffering from LBCLs (diffuse LBCL NOS [n = 196], and high-grade B-cell lymphoma with MYC and BCL2 rearrangements [n = 24]) subtypes, other malignancy subtypes (n = 510) and non-malignant findings (n = 70). For the series of LBCLs, the overall diagnostic accuracy of the micro-histological sampling was 100% (95% confidence interval: 98%-100%). The complications occurred with very low incidence and severity (grade ≤2).

Conclusion: US-guided CNB is a less invasive method and can be considered an alternative to EB for LBCL diagnosis.

Introduction: In chronic myeloid leukemia patients, second-line treatment requires careful consideration of response and tolerability. As most patients need a more efficient tyrosine kinase inhibitor, ponatinib at a lowered dose should be evaluated in this setting.

Methods: We studied a lowered dose of 30 mg ponatinib in second line in patients selected toward a low cardiovascular risk. In 22 screened patients, ponatinib was started in 18 patients previously treated with imatinib (n = 3), dasatinib (n = 9), or nilotinib (n = 6). Patients were frequently monitored for cardiovascular toxicities by testing of blood pressure, vital signs, ankle brachial index or duplex, oral glucose tolerance test, echocardiography, ECG, and fundoscopy. The study protocol allowed dose reductions in patients achieving MMR. Both previously resistant or intolerant patients were recruited.

Results: No serious cardiovascular events were observed, and low-grade cardiovascular toxicity was negligible. By 12 months, 13 patients (92.9%) were in complete hematologic remission, 10 patients (55.6%) were in MMR, and 5 patients (27.8%) were in MR4. Most importantly, we demonstrated that thorough monitoring of cardiovascular risk is feasible.

Conclusions: We demonstrated that a lowered dose of 30 mg ponatinib in selected patients can be maintained without serious cardiovascular complications, provided cardiovascular risk monitoring is performed. In our patient cohort, this approach resulted in favorable response rates.

Introduction: The standard induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) is 7 days cytarabine and 3 days daunorubicin. However, older and frail patients cannot be treated intensively. Before hypomethylating agents (HMA) plus venetoclax (VEN) was established we formulated a more tolerable induction therapy for these patients using continuous infusions of reduced doses of cytarabine (A) and idarubicin (IDA) in combination with ATRA (A), the (A)-AIDA regimen and trying to reach noteworthy and relevant remission rates with acceptable toxicities in this special population.

Methods: Between 1998 and 2015 older/frail patients with newly diagnosed or relapsed AML received (A)-AIDA. Treatment consisted of cytarabine 100 mg/m2/d d1-5 and IDA 5 mg/m2/d d1-5 as continuous infusion. Since 2003 ATRA (45 mg/m2/d d4-6, 15 mg/m2/d d7-28) was added in some patients.

Results: 154 patients received (A)-AIDA, median age was 71 years. In 40% the AML was secondary, 15.6% had relapsed AML. The complete remission rate was 41%, 7% reached a partial remission, the median overall survival was 7 months. No significant differences of remission rates regarding various known risk factors for outcome with (A)-AIDA were detected.

Conlusion: Recent studies established HMA/VEN as first-line treatment for older/frail AML patients. Because (A)-AIDA is equally effective in patients with secondary or relapsed AML or ECOG >1, this regimen is an interesting treatment option for patients uneligible to HMA/VEN regimens.

Introduction: Acquired hemophilia A (AHA) is a severe bleeding disorder, sometimes linked to plasma cell dyscrasias. In this context, emicizumab, a bispecific antibody, provides stable hemostasis by mimicking factor VIII (FVIII), offering convenience and flexibility compared to bypassing agents. Moreover, targeted anti-myeloma therapy directly addresses the underlying plasma cell disorder, potentially achieving better and more durable control of AHA than conventional immunosuppressive therapy, while reducing its associated adverse effects.

Case presentation: We describe the successful management of AHA secondary to multiple myeloma (MM) using emicizumab and targeted anti-myeloma therapy. The patient initially responded to bortezomib-dexamethasone but required teclistamab due to disease progression. Emicizumab maintained hemostatic stability, allowing time for effective MM management.

Conclusion: Emicizumab, in conjunction with targeted myeloma treatment, represents a promising strategy to improve outcomes for AHA patients with MM. This approach is particularly advantageous for older patients with multiple comorbidities, who face elevated risks of thrombotic, bleeding, and infectious complications.