Search

Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial alliance/CALGB 50303. The latter do not carry concurrent c-myc/bcl-2 and/or bcl-6 rearrangements and usually have the morphology of HGBL with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (HGBL-DLBCL/BL). Dear Editor, In the 2016 WHO classification, HGBL was defined as a separate entity, classified into double/triple-hit lymphomas and HGBL not otherwise specified (HGBL-NOS). [Extracted from the article]

Pediatric-inspired chemotherapy significantly improves survival for adolescent and adult patients with acute lymphoblastic leukemia (ALL). However, the benefits over allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. To compare clinical outcomes between pediatric-inspired chemotherapy and allo-HSCT in consolidation therapy of adolescent and adult Philadelphia chromosome-negative (Ph-neg) ALL in first complete remission (CR1), related studies from MEDLINE, Embase, and Cochrane Controlled Register of Trials updated to July 2022 were searched. A total of 13 relevant trials including 3161 patients were included in the meta-analysis. Compared with allo-HSCT, pediatric-inspired chemotherapy achieved better OS (hazard risk (HR), 0.53; 95% confidence interval (CI), 0.41 to 0.68) and DFS (HR, 0.64; 95% CI, 0.48 to 0.86), with a significant reduction in NRM (risk ratio (RR), 0.30; 95% CI, 0.18 to 0.51), but no difference in the relapse rate (RR, 1.13; 95% CI, 0.93 to 1.39). When only studies based on intention-to-treat analysis were included, pediatric-inspired chemotherapy consistently conferred a survival advantage. In subgroup analyses, patients with baseline high-risk features demonstrated similar OS and DFS between pediatric-style chemotherapy and allo-HSCT, while pediatric-style chemotherapy had an OS and DFS advantage in standard-risk subgroup. Particularly, patients with positive minimal residual disease (MRD) achieved better OS and DFS if proceeded to allo-HSCT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There have been several clinical studies using chimeric antigen receptor (CAR)-T cell therapy for different hematological malignancies. It has transformed the therapy landscape for hematologic malignancies dramatically. Nonetheless, in acute myeloid leukemia (AML) and T cell malignancies, it still has a dismal prognosis. Even in the most promising locations, recurrence with CAR-T treatment remains a big concern. Oncolytic viruses (OVs) can directly lyse tumor cells or cause immune responses, and they can be manipulated to create therapeutic proteins, increasing anticancer efficacy. Oncolytic viruses have been proven in a rising number of studies to be beneficial in hematological malignancies. There are limitations that cannot be avoided by using either treatment alone, and the combination of CAR-T cell therapy and oncolytic virus therapy may complement the disadvantages of individual application, enhance the advantages of their respective treatment methods and improve the treatment effect. The alternatives for combining two therapies in hematological malignancies are discussed in this article. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is the most prevalent form of pediatric leukemia. The gut microbiome (GM) is crucial for proper nutrition, immunity, and biological conflict. Since the relationship between ALL and GM is bidirectional, ALL occurrence and treatment are closely related to GM destruction and the development of impaired immunity. Studies have discovered significant GM alterations in patients with ALL, including decreased diversity, that are likely directly caused by the development of ALL. Chemotherapy, antibiotic therapy, and hematopoietic stem cell transplantation (HSCT) are the mainstays of treatment for pediatric ALL. These approaches affect the composition, diversity, and abundance of intestinal microorganisms, which in turn affects therapeutic efficiency and can cause a variety of complications. Modulating the GM can aid the recovery of patients with ALL. This article discusses the various treatment modalities for pediatric ALL and their corresponding effects on the GM, as well as the changes in the GM that occur in children with ALL from diagnosis to treatment. Gaining a greater understanding of the link between ALL and the GM is expected to help improve treatment for pediatric ALL in the future. [ABSTRACT FROM AUTHOR]

To compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) and rhG-CSF in the recovery of neutrophils after induction therapy in ALL patients, PEG-rhG-CSF was injected subcutaneously within 24 ~ 48 h after the end of intravenous infusion of daunorubicin/idarubicin during induction chemotherapy. In rhG-CSF group, patients were given rhG-CSF. The main outcome indexes were the incidence and duration of grade 4 chemotherapy-induced-neutropenia (CIN, ANC less than 0.5 × 10 9 /L), the incidence of severe agranulocytosis (ANC less than 0.2 × 10 9 /L). The incidence of grade 4 CIN in the PEG-rhG-CSF group was significantly lower than that in the rhG-CSF group (P = 0.007). There was no significant difference in the incidence of severe neutrophil deficiency and the median time of neutrophil deficiency in PEG-rhG-CSF group and rhG-CSF group. There was no significant difference in day 28 complete response (CR) rate of bone marrow cytology between the two groups (P = 0.985). Compared with rhG-CSF, PEG-rhG-CSF can reduce the incidence of agranulocytosis after induction chemotherapy in newly diagnosed ALL patients, without affecting the efficacy of chemotherapy. Meanwhile, it can reduce the pain of patients, with good safety and tolerance., Competing Interests: Declarations. Ethical approval: The retrospective, observational study was approved by the Ethics Committee of Qilu Hospital, Shandong University, and was conducted in accordance with the Declaration of Helsinki. All authors of this article agree to publish in your journal. Consent to participate: The Ethics Committee of Qilu Hospital approved waiving the need to obtain written informed consent from each participant. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Myeloid sarcoma (MS) is an extramedullary localization of immature granulocyte cells that can occur in association with acute myeloid leukemia (AML). Gastrointestinal involvement is relatively common in MS, but exclusive colonic localization is a rare occurrence. Here, we report on a 53-year-old male patient affected by AML developing a severe abdominal pain caused by intestinal perforation requiring surgical intervention. The post-mortem examination revealed an infiltrate consistent with MS. Diagnosis of colonic MS can be difficult due to non-specific symptoms and complicated by the challenges associated with exploring this area. Clinical acumen is crucial to promptly establish adequate management due to the potentially life-threatening nature of this condition., Competing Interests: Declarations. Ethical approval and consent to Participate: Informed consent was obtained at first hospital admission according to the protocols approved by the Institutional Review Board and in accordance with the ethical principles set forth by the Declaration of Helsinki. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Various prognostic models have been proposed to improve the accuracy of prognostic assessment for Myelodysplastic syndromes (MDS). Recently, the Molecular International Prognostic Scoring System (IPSS-M) has been developed. Here, we validated the accuracy of IPSS-M in Chinese MDS patients, and proposed a prognostic model more suitable for Chinese patients. We analyzed the clinical, molecular and cytogenetic data of 798 primary MDS patients, and compared the accuracy of IPSS-R and IPSS-M in predicting overall survival (OS) and acute myeloid leukemia (AML) transformation. Using Cox proportional hazards model, we screened out 14 genes that had significant impacts on OS and AML progression. In our study, 44.86% of individuals were reclassified from IPSS-R to IPSS-M, of whom 64.80% were upstaged and 35.2% were downstaged. IPSS-M showed better performance than IPSS-R in predicting AML transformation (C-index: 0.84 vs. 0.81), but it was similar to IPSS-R in OS (C-index: 0.77 vs. 0.76). By combining age, mutational data and IPSS-R, we developed a new prognostic model more suitable for the Chinese patients (c-index was 0.81 for OS and 0.89 for AML transformation, respectively)., Competing Interests: Declarations. Ethical approval: This study was approved by the ethics committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. This study has registered in Chinese Clinical Trial Center (Registration number: ChiCTR2300074952). All patients provided written informed consent in conformity with the Declaration of Helsinki. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Blinatumomab has shown to improve survival outcomes in B-cell acute lymphoblastic leukemia (B-ALL) patients with measurable residual disease (MRD) detected by multiparametric flow cytometry (MFC). However, data on blinatumomab clearing MRD with high sensitivity remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating low levels of MRD, as detected by droplet digital PCR (ddPCR) but undetectable by MFC, in children with B-ALL. Patients (n = 9) whose MRD was undetectable by MFC but detectable by ddPCR after chemotherapy and followed by blinatumomab consolidation were included retrospectively. After the administration of blinatumomab, 5 out of 9 patients (55.56%) successfully achieved undetectable levels of ddPCR-MRD. Notably, among the 4 patients with BCR::ABL1 gene-positive acute lymphoblastic leukemia (ALL), only one achieved gene negativity. Starting from the initiation of blinatumomab treatment, with a median follow-up of 12 months, all patients remained in complete remission. Our study was the first to demonstrate that blinatumomab could further eradicate ddPCR MRD after patients achieve MFC-MRD undetectable status in B-ALL patients., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. The studies involving human participants were reviewed and approved by the Ethics Committee of Shenzhen Children’s Hospital.Written informed consent was obtained from the parents. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Central nervous system leukemia (CNSL) and central nervous system infection (CNSI) are the most important complications in patients with acute leukemia (AL). However, the differential diagnosis could represent a major challenge since the two disorders are all heterogeneous entities with overlapping clinical characteristics and radiological appearances. In this paper, we conduct a retrospective study to develop a model based on clinical data and magnetic resonance imaging (MRI) to distinguish CNSL from CNSI. A total of 108 patients with AL who underwent cranial MRI between January 2020 and December 2023 in our hospital were included. Univariate and multivariate logistic regression analyses were used to determine the independent predictors. A nomogram was developed based on the predictors, and the performance of the nomogram was evaluated by the area under the receiver operating characteristic (ROC) curve. The validation cohort was used to test the predictive model. Hyperleukocytosis at initial diagnosis, marrow state, fever, conscious disturbance, coinfection in other sites and MRI (parenchyma type) were identified as independent factors. A nomogram was constructed and the discrimination was presented as AUC = 0.947 (95% CI 0.9105-0.984). Calibration of the nomogram showed that the predicted probability matched the actual probability well., Competing Interests: Declarations. Ethics approval and consent to participate: The study received approval from the institutional review board of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (IRB number: QTJC2024036-EC-1). The informed consent was waived due to the retrospective design of the research. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Improved understanding of TP53 biology and the clinicopathological features of TP53-mutated myeloid neoplasms has led to the recognition of TP53-mutated acute myeloid leukemia/myelodysplastic syndrome (TP53m AML/MDS) as a unique entity, characterized by dismal outcomes following conventional therapies. Several clinical trials have investigated combinations of emerging therapies for these patients with the poorest molecular prognosis among myeloid neoplasms. Although some emerging therapies have shown improvement in overall response rates, this has not translated into better overall survival, hence the notion that p53 remains an elusive target. New therapeutic strategies, including novel targeted therapies, immune checkpoint inhibitors, and monoclonal antibodies, represent a shift away from cytotoxic and hypomethylating-based therapies, towards approaches combining non-immune and novel immune therapeutic strategies. The triple combination of azacitidine and venetoclax with either magrolimab or eprenetapopt have demonstrated safety in early trials, with phase III trials currently underway, and promising interim clinical results. This review compiles background on TP53 biology, available and emerging therapies along with their mechanisms of action for the TP53m disease entity, current treatment challenges, and recently published data and status of ongoing clinical trials for TP53m AML/MDS. [ABSTRACT FROM AUTHOR]

Interim 18F-FDG PET/CT (I-PET) has a role in response evaluation and treatment guidance in patients with nasal-type extranodal natural killer/T cell lymphoma (ENKTL). However, there was no agreement on the timing of I-PET performed, after chemotherapy or after chemoradiotherapy. We aimed to find the appropriate timing for I-PET by assessing the prognostic value of I-PET in response evaluation in ENKTL patients. Two hundred and twenty-seven ENKTL patients who had undergone I-PET were retrospectively included. All patients were grouped based on their therapeutic strategy received, chemotherapy or chemoradiotherapy. The Deauville 5-point score (DS) was used to interpret the I-PET images. The hazard ratio (HR) and C-index were used to measure the discriminatory and prognostic capacities of I-PET performed at different times. One hundred and six patients underwent the I-PET after chemotherapy (chemotherapy group), while I-PET was performed after chemoradiotherapy in 121 patients (chemoradiotherapy group). Eighty-seven patients were classified as metabolic remission (DS score of 1–3), while the other 140 were classified as non-metabolic remission (DS score of 4–5) according to the Deauville criteria. There were no significant survival differences between patients in metabolic remission and in non-metabolic remission in either progression-free survival (PFS, p = 0.406) or overall survival (OS, p = 0.350). In the chemotherapy group, patients in metabolic remission had significantly superior PFS than patients in non-metabolic remission (p = 0.012). For OS, a discriminative trend was also found on the survival curve between patients in metabolic remission and in non-metabolic remission (p = 0.082). In the chemoradiotherapy group, there was no significant difference in PFS (P = 0.185) or OS (P = 0.627) between patients in metabolic remission and in non-metabolic remission. I-PET after chemotherapy yields higher discriminative power and has the ability for prognostic prediction in nasal-type ENKTL patients. I-PET after radiochemotherapy has no prognostic value. Thus, the appropriate timing for I-PET is after chemotherapy but before radiotherapy for response evaluation in nasal-type ENKTL patients. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the role of the combination of volumetric and dissemination parameters obtained from pretreatment 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting the interim response and progression status in patients with Hodgkin lymphoma (HL). Pretreatment PET/CT images of HL patients were analyzed with LIFEx software, and volumes of interest (VOIs) were drawn with a fixed SUV 4.0 threshold. MTV, SUVmax, and TLG values were obtained from each VOI. Total MTV (tMTV) was calculated by summing the MTV values in all VOIs, and similarly, total TLG (tTLG) was obtained by summing the TLG values. The distance between the centers of the lesions was noted as Dmax, and the distance between the outermost voxels of the lesions as DmaxVox. tMTV/DmaxVox was calculated by dividing the tMTV value by the DmaxVox value, and tTLG/DmaxVox was calculated by dividing the tTLG value by the DmaxVox value. The correlation of pretreatment PET parameters with response groups (complete/poor) and relapse/progression status (stable/progressive) was statistically evaluated. A total of 52 patients were included in the study. Bulky disease, tMTV, tTLG, and tMTV/DmaxVox values were found to be significantly higher in the poor response group. tMTV > 190.60 ml was found to be the only prognostic factor predicting interim PET response. The tMTV/DmaxVox and tTLG/DmaxVox showed statistically significant differences between the groups with and without progression. tMTV/DmaxVox > 7.70 was found to be the only prognostic factor in predicting relapse/progression. The evaluation of tumor burden and dissemination together in 18F-FDG PET/CT before treatment in patients with HL can help us to predict the results of the patients. [ABSTRACT FROM AUTHOR]

The anti-PD-1 antibodies have been reported to show a striking effect in relapsed and refractory(R/R) classical Hodgkin lymphoma (cHL), however, there is still limited real-world data assessing the role of anti-PD-1 antibody monotherapy in early-stage cHL. In this retrospective analysis, we reported the effectiveness and safety of tislelizumab monotherapy in the first-line therapy of early-stage cHL. Twenty-three consecutive patients (10 males and 13 females) with previously untreated stage I A-II B cHL were included. At interim evaluation after 2 doses of tislelizumab monotherapy, 11 of 23 patients (47.8%) achieved complete response (CR). At the end of tislelizumab monotherapy (EOTM), objective response was observed in 22 of 23 patients (95.7%), with CR in 16 patients (69.6%). Among six patients with PR-EOTM, two patients underwent 4 cycles of ABVD chemotherapy and one patient underwent 4 cycles of tislelizumab plus AVD. One patient who developed progressive disease (PD) after 4 doses of tislelizumab subsequently underwent 4 cycles of ABVD chemotherapy. Except for four patients with CR-EOTM, consolidative radiotherapy was given to 19 patients. All patients obtained CR at the end of all treatments. With a median follow-up time of 21.3 months (range, 6.9–32.7 months), the estimated 2-year PFS rate and 2-year OS rate were 95.65% and 100%, respectively. Except for grade 3 lymphocyte count decreased, no other grade 3/4 TRAE was observed. In addition, no serious AE was reported. Our preliminary data observed that tislelizumab monotherapy was safe and highly effective in previously untreated early-stage cHL. [ABSTRACT FROM AUTHOR]

We diagnosed CL comprising diffuse large B-cell lymphoma (DLBCL) and nodal peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH), according to the revised 2017 World Health Organization (WHO) classification [[3]]. Dear Editor, Composite lymphoma (CL) is defined as two or more distinct lymphoma subtypes in a single anatomic tissue or the same lymph node, while discordant lymphoma is two or more distinct lymphoma subtypes existing at different sites simultaneously [[1]]. [Extracted from the article]

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive B-cell non-Hodgkin lymphoma that poses a great diagnostic challenge due to its highly heterogenous clinical manifestations. Although 18F-fluorodeoxyglucose (FDG) is widely used as a diagnostic tool for patients suspected of having lymphoma, as it reveals FDG-avid lesions, the FDG avidity of IVLBCL has not been extensively characterized. Here, we present a comprehensive report of FDG avidity in IVLBCL and its association with clinicopathological features and survival. This descriptive observational study included consecutive patients aged at least 18 years diagnosed with IVLBCL in Peking Union Medical Hospital across 9 years. Among 50 screened IVLBCL patients, 42 had undergone 18F-FDG PET/CT to detect possible lesions for biopsy before pathological diagnosis; their FDG PET/CT (positron emission computed tomography, PET/CT) reports were retrospectively reviewed. The primary endpoint was the clinical description of FDG avidity of newly diagnosed intravascular large B-cell lymphoma and frequency. A total of 73.8% patients showed FDG-avid lesions, with a median SUVmax of 7.4 (range 1–27.7), which was lower than that for other aggressive lymphomas. Clinicopathological features were the same between the FDG-avid group and the non-FDG-avid group, except that the latter had a higher Ki-67 index (median 90% in the nonavid group vs. 80% in the avid group, P = 0.043). The overall survival rate was not different between the PET/CT groups. Our findings demonstrate that FDG PET/CT is a useful diagnostic tool for detecting FDG-avid lesions in IVLBCL patients. A random skin biopsy is essential for assisting in the diagnosis of IVLBCL, even for those with negative PET/CT. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the incidence rate and spectrum of gene mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Huizhou city of southern China to provide a scientific basis for disease prevention and control in the area. Methods: From March 2003 to December 2022, newborn screening for G6PD enzyme activity was carried out in Huizhou city using the fluorescence quantitative method. Infants who tested positive during the initial screening were diagnosed using the nitroblue tetrazolium ratio method, while a subset of infants received further gene mutation analysis using the multicolor probe melting curve analysis method. Results: A total of 1,291,274 newborns were screened and the screening rate has increased from 20.39% to almost 100%. In the 20-year period, 57,217 (4.43%) infants testing positive during the initial screening. Out of these infants, 49,779 (87%) were recalled for confirmatory testing. G6PD deficiency was confirmed in 39,261 of the recalled infants, indicating a positive predictive value of 78.87%. The estimated incidence rate of G6PD deficiency in the region was 3.49%, which was significantly higher than the average incidence rate of 2.1% in southern China. On the other hand, seven pathogenic G6PD variants were identified in the analysis of the 99 diagnosed infants with the most common being c.1388 G > A (48.5%), followed by c.95 A > G (19.2%), c.1376 G > T (15.2%), c.871 G > A (9.1%), c.1360 C > T (3.0%), c.392 G > T (3.0%), and c.487 G > A (1.0%). Conclusion: The incidence of G6PD deficiency in newborns in the Huizhou city was higher than the southern China average level, while the types and frequencies of gene mutations were found to vary slightly from other regions. Our findings suggested that free government screening and nearby diagnosis strategies could reduce the incidence of G6PD deficiency in the area. [ABSTRACT FROM AUTHOR]

Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUVmax, ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4–5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUVmax, ΔTMTV and ΔTLG, only a ΔSUVmax ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11–0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUVmax ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUVmax to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification. [ABSTRACT FROM AUTHOR]

Dear Editor, Whereas outcome in younger patients with acute B-lymphoblastic leukemia (B-ALL) improved over the last decades, prognosis for older patients, especially with relapsed or refractory (r/r) disease, remains particularly dismal [[1]]. Our case report demonstrates efficacy and tolerability of CD19-directed CAR T cell therapy in an elderly patient with r/r B-ALL. This case report demonstrates that novel immuno-salvage therapies represent an effective, safe, and feasible treatment option in older patients with r/r B-ALL without impairment of their quality of life. [Extracted from the article]

IKZF1 deletion is a recurrent genomic alteration in B-cell acute lymphoblastic leukemia (B-ALL) and is divided into dominant-negative (DN) and loss of function (LOF) deletions. The prognostic impact of each deletion has not been fully elucidated. We retrospectively analyzed 117 patients with adult B-ALL including 60 patients with BCR::ABL1-positive B-ALL and 57 patients with BCR::ABL1-negative B-ALL by the fluorescence in situ hybridization (FISH) method for IKZF1 deletion and multiplex PCR for the 4 most common IKZF1 deletions (∆4–7, ∆2–7, ∆2–8, and ∆4–8). Samples, in which IKZF1 deletion was detected by FISH but a specific type of deletion was not identified by the PCR, were categorized as "other." Patients were classified into a DN group that had at least 1 allele of ∆4–7 (n = 23), LOF and other group (n = 40), and wildtype group (n = 54). DN type IKZF1 deletions were found in 33.3% of BCR::ABL1-positive cases and 5.2% of BCR::ABL1-negative cases. LOF and other type IKZF1 deletions were found in 43.4% of BCR::ABL1-positive cases and 24.6% of BCR::ABL1-negative cases. Patients with the DN group showed significantly higher overall survival (OS) than that of the LOF and other and WT groups (P = 0.011). Multivariate analysis including age, WBC counts, complex karyotype, and DN type IKZF1 deletion showed that the DN type of IKZF1 deletion (HR = 0.22, P = 0.013) had a positive impact and age ≥ 65 (HR = 1.92, P = 0.029) had a negative impact on OS. The prognostic impact of IKZF1 deletion depends on the type of deletion and DN type of IKZF1 deletion showed better prognosis in adult B-ALL patients. Clinical trial registration This study was part of a prospective observational study (Hokkaido Leukemia Net, UMIN000048611). It was conducted in compliance with ethical principles based on the Helsinki Declaration and was approved by the institutional review board of Hokkaido University Hospital (#015–0344). [ABSTRACT FROM AUTHOR]

The incorporation of pediatric-inspired regimens in the adolescent-young-adult (AYA) and adult populations have resulted improved survival outcomes (Stock et al. Blood 133(14):1548–1559 2019; Dunsmore et al. J Clin Oncol 38(28):3282–3293 2020; DeAngelo et al. Leukemia 29(3):526-534 2015). Nonetheless incorporation of such regimens is limited by increased toxicity to asparaginase. Dosing strategies that reduce the weight-based dose of pegylated-L-asparaginase (PEG-asparaginase) utilizing activity monitoring have been shown to result in better tolerability of these regimens. The purpose of this study was to analyze the efficacy and safety of treating adults with Philadelphia chromosome negative (Ph−) ALL with pediatric-inspired regimens that incorporate PEG-asparaginase dose adjustments and asparaginase activity level monitoring. Patients aged 18–65 years initiated on pediatric-inspired regimens utilizing dose-reduced PEG-asparaginase with therapeutic drug monitoring-guided adjustments were included. The screening of 122 patients treated between 2015 and 2021 resulted in the inclusion of 54 patients. The median age of the cohort was 35 years (16–65 years), and median body mass index (BMI) was 30 kg/m2 (18.3–53.4 kg/m2). The 36-month survival estimate was 62.1% (95% CI 48.1–77.7%), and the median overall survival (OS) was 62.2 months (95% CI 35.1–89.3 months). In the AYA cohort, the 36-month survival was 71.2% (95% CI 55.8–91%) and the median overall survival was not reached. Survival was not significantly affected by immunophenotype or BMI. Discontinuation due to toxicity or hypersensitivity reactions was low at 11% and 9% respectively. The encouraging survival outcomes and favorable tolerability of this older population in the real-world setting support the use of individualized PEG-asparaginase dosing with PharmD-guided therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the clinical and prognostic role of body composition and metabolic parameters extracted from baseline 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively collected the clinicopathological and 18F-FDG PET/CT parameters of 181 DLBCL patients. The indexes of skeletal muscle, subcutaneous adipose tissue, and visceral adipose tissue were calculated using the area measured at the 3rd lumbar level normalized for height. Additionally, the metabolic activity of corresponding muscle and adipose tissue, and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of all lesions were measured. Survival endpoints included progression-free survival (PFS) and overall survival (OS). We identified 75 (41.4%) patients with low skeletal muscle index (sarcopenia), presenting risk factors including male, high β2-microglobulin, low BMI, high visceral adipose tissue index, low SUVmax of skeletal muscle, and high SUVmax of visceral adipose tissue. Male, low BMI, low visceral adipose tissue index, and high SUVmax of subcutaneous adipose tissue were risk factors for low subcutaneous adipose tissue index diagnosed in 105 (58.0%) patients. In total, 132 (79.2%) patients represented low visceral adipose tissue index, associated with younger age, B symptoms, and low BMI. Eastern Cooperative Oncology Group (ECOG) status, sarcopenia, and visceral adipose tissue index were found independently predictive of PFS and OS, while β2-microglobulin was independently predictive of OS. In conclusion, body composition indexes were correlated with both clinical characteristics and 18F-FDG PET/CT metabolic parameters, significantly impacting survival, such that sarcopenia and high visceral adipose tissue index were powerful predictors of poor DLBCL outcomes. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) is the standard treatment of primary refractory or relapsed Hodgkin-lymphoma, which can provide a cure rate of about 50%. The aim of our study was to analyze the data of 126 HL patients undergoing AHSCT in Hungary between 01/01/2016 and 31/12/2020. We assessed the progression-free and overall survival, the prognostic role of PET/CT performed before transplantation and effect of brentuximab vedotin (BV) treatment on survival outcomes. The median follow-up time from AHSCT was 39 (1–76) months. The 5-year OS comparing PET- and PET + patients was 90% v. 74% (p = 0.039), and 5-year PFS was 74% v. 40% (p = 0.001). There was no difference in either OS or PFS compared to those who did not receive BV before AHSCT. We compared BV treatments based on their indication (BV only after AHSCT as maintenance therapy, BV before and after AHSCT as maintenance treatment, BV only before AHSCT, no BV treatment). There was statistically significant difference in the 5-year PFS based on the inication of BV therapy. Recovery rates of our R/R HL patient population, who underwent AHSCT, improved significantly. Our positive results can be attributed to the PET/CT directed, response-adapted treatment approach, and the widespread use of BV. [ABSTRACT FROM AUTHOR]

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1–2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 69-year-old man with the multicentric ileal extraosseous plasmacytomas (EPs) with the medical history of difuse large B cell lymphoma (DLBCL). It discusses the observations including multicentric flat tumors, performance of the end-to-end anastomoses resection.

T cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive malignancy of progenitor T cells. Despite significant improvements in survival of T-ALL/LBL over the past decades, treatment of relapsed and refractory T-ALL (R/R T-ALL/LBL) remains extremely challenging. The prognosis of R/R T-ALL/LBL patients who are intolerant to intensive chemotherapy remains poor. Therefore, innovative approaches are needed to further improve the survival of R/R T-ALL/LBL patients. With the widespread use of next-generation sequencing in T-ALL/LBL, a range of new therapeutic targets such as NOTCH1 inhibitors, JAK-STAT inhibitors, and tyrosine kinase inhibitors have been identified. These findings led to pre-clinical studies and clinical trials of molecular targeted therapy in T-ALL/LBL. Furthermore, immunotherapies such as CD7 CAR T cell therapy and CD5 CAR T cell therapy have shown profound response rate in R/R T-ALL/LBL. Here, we review the progress of targeted therapies and immunotherapies for T-ALL/LBL, and look at the future directions and challenges for the further use of these therapies in T-ALL/LBL. [ABSTRACT FROM AUTHOR]

Therapy results in pediatric Hodgkin lymphoma reflect remarkable progress in pediatric oncology. In the last decade, relevant development of new therapeutic options for children with refractory or relapsed disease has been made. In this study, we retrospectively analyzed therapy results and risk factors in children treated in a single oncology center according to five therapeutic protocols. Data from 114 children treated by a single institution between 1997 and 2022 were analyzed. Classic Hodgkin lymphoma therapy results were divided into four therapeutic periods: 1997–2009, 2009–2014, 2014–2019, and 2019–2022. For nodular lymphocyte-predominant Hodgkin lymphoma, data from one therapeutic protocol was analyzed. For the entire group, the 5-year probability of overall survival was 93.5%. There were no statistically significant differences between therapeutic periods. The occurrence of B symptoms at diagnosis and incidence of relapse were risk factors for death (p = 0.018 and p < 0.001). Relapse occurred in 5 cases. The 5-year probability of relapse-free survival for the entire group was 95.2%, without significant differences between groups. Patients treated between 1997 and 2009 had over a sixfold higher risk for events, defined as primary progression, relapse, death, or incidence of secondary malignancies (OR = 6.25, p = 0.086). The 5-year probability of event-free survival for all patients was 91.3%. Five patients died, and the most common cause of death was relapse. Modern therapeutic protocols in pediatric Hodgkin lymphoma are marked by excellent outcomes. Patients with disease relapses have a notably high risk of death, and the development of new therapeutic options for this group remains one of the main goals of current trials. [ABSTRACT FROM AUTHOR]

Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is a challenging condition to treat, and there is an unmet clinical need for effective therapies. Recently, polatuzumab vedotin (Pola), an anti-CD79b antibody-drug-conjugate (ADC), combined with bendamustine-rituximab (BR), has been approved for R/R DLBCL patients. However, real-world data on Pola-based regimens in R/R DLBCL patients, especially in Thailand, are limited. This study aimed to evaluate the efficacy and safety of Pola-based salvage treatment in R/R DLBCL patients in Thailand. Thirty-five patients who received Pola-based treatment were included in the study, and their data were compared to 180 matched patients who received non-Pola-based therapy. The overall response rate (ORR) in the Pola group was 62.8%, with complete remission and partial remission rates of 17.1% and 45.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 10.6 months and 12.8 months, respectively. The study found a significantly higher ORR in Pola-based salvage treatments compared to non-Pola-based therapy (62.8% vs. 33.3%). The survival outcomes were also significantly superior in the Pola group, with longer median PFS and OS than the control group. Grades 3–4 adverse events (AEs) were mainly hematological, and they were tolerable. In conclusion, this study provides real-world evidence of the efficacy and safety of Pola-based salvage treatment in R/R DLBCL patients in Thailand. The results of this study are promising and suggest that Pola-based salvage treatment could be a viable option for R/R DLBCL patients who have limited treatment options. [ABSTRACT FROM AUTHOR]

Primary mediastinal large B-cell lymphoma is a rare subtype of lymphoma. The contemporary incidence of primary mediastinal large B-cell lymphoma remains unknown, and a large population-based study has not been reported. It is essential to provide guidance for further strategies in reducing the disease burden via population-based preventive initiatives. This study aims to explore the epidemiology and effect of therapeutic advances on the survival of patients with primary mediastinal large B-cell lymphoma. This population-based study was conducted using the Surveillance, Epidemiology, and End Results Program (SEER), covering the period from 1975 to 2018. A total of 774 patients in the SEER 9 and 1654 patients in the SEER 18 were analyzed. The age-adjusted incidence rate of primary mediastinal large B-cell lymphoma increased from 0.05/1,000,000 in 1975 to 2.38/1,000,000 in 2018. A significant positive linear increase in the incidence trend was found in primary mediastinal large B-cell lymphoma, with an annual percent change of 8.47% (95% confidence interval 7.7-9.2%, P < 0.001, z test). The survival in primary mediastinal large B-cell lymphoma was significantly superior to nodal diffuse large B-cell lymphoma. The incidence of PMBCL increases over the year. The survival of patients with primary mediastinal large B-cell lymphoma has improved over time. [ABSTRACT FROM AUTHOR]

Hepatosplenic T cell lymphoma (HSTCL) is a rare and aggressive lymphoma with no standard treatment and poor treatment response. From 2001–2021, 20 from a lymphoma cohort of 7247 patients (0.27%) were diagnosed with HSTCL at Samsung Medical Center. The median age at the time of diagnosis was 37.5 (range, 17–72) years, and 75.0% of patients were male. Most patients had B symptoms, hepatomegaly, and splenomegaly. Lymphadenopathy was found in only 31.6% of patients, and increased PET-CT uptake was found in 21.1% of patients. Thirteen patients (68.4%) expressed T cell receptor (TCR) γδ, and 6 patients (31.6%) expressed TCRαβ. The median progression-free survival (PFS) for the entire cohort was 7.2 months (95% CI, 2.9–12.8), and the median overall survival (OS) was 25.7 months (95% CI, not calculated). In subgroup analysis, the overall response rate (ORR) was 100.0% in the ICE/Dexa group and 53.8% in the anthracycline-based group, and the complete response rate was 83.3% in the ICE/Dexa group and 38.5% in the anthracycline-based group. The ORR was 50.0% in the TCRαβ group and 83.3% in the TCRγδ group. The OS was not reached in the autologous hematopoietic stem cell transplantation (HSCT) group and was 16.0 months (95% CI, 15.1–16.9) in the non-transplant group at the data cutoff time (P value 0.015). In conclusion, HSTCL is rare but has a very poor prognosis. The optimal treatment strategy is not defined. More genetic and biological information is needed. [ABSTRACT FROM AUTHOR]

Previous studies have shown that socioeconomic factors play an important role in multiple myeloma (MM) health outcomes. We postulated that the type of treatment facilities and their volume of cases also affect overall survival, utilization of various therapies including palliative care services in newly diagnosed MM. Using the National Cancer Database (NCDB), we analyzed 174,551 newly diagnosed MM participants from across the country. We found that at high volume facility centers (over 90th percentile of new patient volume from 2004 to 2016), the median overall survival (OS) was 62.3 months versus 35.3 months at lower volume facilities (p <0.001). Similarly, high volume academic cancer centers had an improved median OS of 66.4 months (65.3–67.4 CI) versus 39.2 months (37.9–40.4 months CI) in lower volume academic centers (p <0.001). The odds of utilizing chemotherapy, immunotherapy, and autologous transplants were higher in academic cancer centers compared to community cancer centers, after adjusting for demographic and socioeconomic factors (OR 1.10, 1.23, and 2.06 respectively, all with p<0.001). There was significantly decreased odds of receiving palliative care (OR 0.89, 95% CI 0.85–0.93) in high volume facilities compared to low volume. Palliative care services were more frequently utilized at integrated network cancers and comprehensive community cancer centers compared to community cancer centers, with similar odds of receiving palliative care between community and academic facility types. Our results likely reflect increased provider experience and resources in higher volume and academic facilities. This highlights the need to integrate resources and improve access to community programs. [ABSTRACT FROM AUTHOR]

The B cell surface antigen CD19 is a target for treating B cell malignancies, such as B cell precursor acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma. The BiTE® immuno-oncology platform includes blinatumomab, which is approved for relapsed/refractory B cell precursor acute lymphoblastic leukemia and B cell precursor acute lymphoblastic leukemia with minimal residual disease. Blinatumomab is also being evaluated in combination with other agents (tyrosine kinase inhibitors, checkpoint inhibitors, and chemotherapy) in various treatment settings, including frontline protocols. An extended half-life BiTE molecule is also under investigation. Patients receiving blinatumomab may experience cytokine release syndrome and neurotoxicity; however, these events may be less frequent and severe than in patients receiving other CD19-targeted immunotherapies, such as chimeric antigen receptor T cell therapy. We review BiTE technology for treating malignancies that express CD19, analyzing the benefits and limitations of this bispecific T cell engager platform from clinical experience with blinatumomab.