bluuebunny/crossref_metadata_2025_split huggingface dataset:
Driving Cell Therapy in Treatment of MRD-Positive Acute Pediatric Lymphoblastic Leukemia after Allogeneic-HSCT: Blinatumomab + DLI
Authors: Rossitti Emanuela , Pagano Gennaro , Cacace Fabiana , Caprioli Valeria , D'Amico Maria Rosaria , De Simone Giuseppina , Sabbatino Maria Simona , Wierda William G. , Tambaro Francesco Paolo Paolo 
Published: December 2024

Background
Persistence of Measurable Residual Disease (MRD &gt; 10-4) in Acute Lymphoblastic Leukemia (ALL) is high risk for relapse after allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with a very dismal prognosis. The role of Donor Lymphocytes Infusion (DLI) in the treatment of MRD-positive ALL is still debated, while favorable results have been observed in the treatment of MRD-positive relapse with the CD3-CD19 bi-specific T cell engager blinatumomab.
Methods
Three pediatric patients with high risk B-ALL were treated according to AEIOP ALL 2009 and AIEOP ALL 2017 protocols and referred for allo-HSCT. Two patients were male. Median age was 16 years (3-17). Patient 1 was primary refractory to 2 lines of chemotherapy and blinatumomab and achieved MRD-positive complete remission (CR) after 2 courses of inotuzumab. Patient 2, affected by secondary ALL, achieved CR1 after 1 course of chemotherapy and subsequently received 2 courses of blinatumomab, due to treatment chemotherapy-associated toxicity, achieving MRD-negative CR1. Patient 3 developed CNS relapse during maintenance, then received salvage therapy according to the INTREALL HR 2010 and 1 course of blinatumomab, achieving MRD-positive CR1.
Results
All patients underwent allo-HSCT and were MRD-positive at 8, 31 and 23 weeks post allo-HSCT, respectively. All patients discontinued immunosuppressive therapy and received 4, 1 and 3 courses of DLI + blinatumomab, respectively. Blinatumomab was started one week after each dose of DLI. Only patient 1 experienced grade 2 liver GvHD. None of the patients experienced serious adverse events needing blinatumomab discontinuation. All 3 patients reached an MRD-negative complete remission (CR). Median follow-up post HSCT was 30 months (11-30). Patient 2 and 3 are still in CR with persistent negative MRD, while patient 1 died for disease relapse (isolated CNS relapse).
Conclusions
The role of cellular therapy with DLI is still debated. Blinatumomab directs T cells to bind CD19 present on malignant B cells and engages CD3 on T cells causing activation and inducing cytotoxicity against the ALL cells. The use of blinatumomab allowed recruitment of fit donor-derived T lymphocytes (not exposed to immune suppressive agents) against ALL B cells. This hypothesis is supported by the fact that patient 1, who received blinatumomab pre-HSCT and had disease progression (probably due to the lack of T cells showed by flow cytometry), achieved MRD-negative response after receiving DLI+blinatumomab post-transplant. All patients reached MRD-negative status and 2 subsequently developed CNS relapse; none received CNS prophylaxis post-HSCT. We hypothesize that blinatumomab + DLI is able to clear the hematological disease, but it is not effective in preventing CNS relapse.
Delayed Physical Growth and Related Factors in Pediatric Patients with Transfusion-Dependent Thalassemia
Authors: Zhao Jingyu , Yu Xiao , Xu Jing , Gao Zhen , Liu Yanjie , Wang Anni , Dong Jin , Yuan Weiping , Shi Jun , Kuang Zhexiang 
Published: December 2024

Objectives To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and assess the clinical and economic factors associated with delayed physical growth.
Methods We extracted sociodemographic and clinical data on 338 pediatric patients with TDT, including physical growth indicators (height and weight), family economic status and disease related treatment, from thalassemia disease database at a grade-A tertiary hematological specialty hospital in China between October 2023 and May 2024. Length/height-for-age and body mass index-for-age (BMI-for-age) were assessed using the ‘Growth Standard for Children under 7 Years of Age’ and the ‘Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years’ issued by the National Health Commission, as well as the ‘Dietary Guidelines for Chinese Residents’. Logistic regression was performed to explore the impact of sociodemographic and clinical factors on length/height-for-age and BMI-for-age, respectively.
Results Among the 338 pediatric patients with TDT, 192 were male and 146 were female, with a median age of 12 (0.8-18.0) years and a median time since diagnosis of 10.3 (0.5-17.9) years. Of these patients, 21 (6.2%) had ⍺ thalassemia, 288 (85.2%) had β thalassemia, and 29 (8.6%) had mixed ⍺ and β thalassemia. Overall, 88 (26.00%) children were stunted as their length/height failing below -2 standard deviations (SDs) from the national growth standard median. There were 95 (28.1%) children with length/height between -2 SDs and -1SD, and 155(45.9%) children with length/height≥-1SD. Meanwhile, 77 (22.8%) patients were underweight, 241 (71.3%) were at a healthy weight, and 20 (5.9%) were classified as overweight/obese based on their BMI-for-age. The majority of TDT children had a family monthly income falling within the ranges of 3000-5000 yuan and 5000-10000 yuan, accounting for 135 (39.9%) and 118 (34.9%) cases, respectively. Pre-transfusion hemoglobin (HGB) levels were categorized as ≤70 g/L, 70-90 g/L, and &gt;90 g/L in 19 (5.6%), 123 (36.4%), and 196 (58.0%) cases, respectively. Thirty (8.9%) pediatric patients exhibited serum ferritin (SF) levels of ≥5000ug/L, 321 (95.0%) received chelation therapy, and 16 (4.7%) underwent splenectomy. Multivariate regression analysis revealed that pre-transfusion HGB≤70g/L, SF≥5000ug/L, and a monthly family income below 10000 yuan were all significantly associated with an increased risk of stunting (all P&lt;0.05). Moreover, a longer time since diagnosis was a hazardous factor for being underweight (P=0.013).
Conclusions Pediatric patients with TDT who had pre-transfusion HGB≤70g/L, SF≥5000ug/L, lower monthly family income or longer time since diagnosis were at a higher risk for delayed physical growth.
Patterns of Vaccine Titers after Childhood Leukemia Treatment
Authors: Kasavaraju Megana , Gowda Madhu 
Published: December 2024

Background
The CDC recommends that all children follow the primary immunization series vaccination schedule to prevent vaccine-preventable diseases. The primary immunization begins at birth and completes at 18 months, with boosters given from 4-6 years old. Acute lymphoblastic leukemia (ALL) is a common childhood cancer which typically affects children from 2-4 years old. The treatment for acute lymphoblastic leukemia (ALL) targets lymphocytes, which are cells that play a role in memory retention for vaccine immunity. The purpose of this experiment is to determine whether there is loss of vaccine immunity in children treated for ALL and whether there is a difference between the high-risk ALL protocols and standard-risk ALL protocols. Understanding loss of immunity in children treated for ALL can help to establish reimmunization guidelines in order to protect survivors from vaccine-preventable diseases.
Methods
This retrospective study consisted of chart reviews of 45 pediatric patients who are ALL survivors at Children's Hospital of Richmond. Titers drawn from these patients were compared to the general population using a one-proportion z-test. The ALL group was then divided into high-risk protocol and standard-risk protocol groups. Titers and lymphocyte enumeration panels were then compared between the two groups using a two-proportion z-test.
Results
The results of this study showed that there was a significantly higher percentage of negative hepatitis B, varicella, MMR, and Dtap titers for the ALL group than in the general pediatric population (p&lt;.01). However, there was no significant difference between children treated with high-risk protocols and standard-risk protocols (p = .42). The standard-risk group had 44% negative titers while the high-risk group had 53%. Additionally, the standard-risk group had 78% abnormal lymphocyte enumeration panel while the high-risk group had 86%.
Conclusion
This study showed that children treated with chemotherapy for ALL lose immunity against vaccine preventable diseases and require reimmunization to protect them from future infection. Additionally, there is no significant statistical difference in immunity between the children treated with high-risk protocols vs standard-risk protocols. However, the percentage of negative titers and abnormal lymphocyte enumeration panels in the high-risk group was greater than the standard-risk group, so there may be some clinical significance. Therefore, routine revaccinations should be implemented after chemotherapy and children treated with high-risk protocols may require more follow-ups and precautions. Limitations of this study include small sample size and possible revaccinations at outside hospital systems. Future studies will look at the rate of lymphocyte recovery in standard vs high-risk protocol groups to further assess impacts of chemotherapy protocols on immunity.
Potent in Vitro and In Vivo Efficacy of Hdz-C123A, a GSPT1 Degrader-Antibody Conjugate Targeting CD123 in Acute Myeloid Leukemia
Authors: Dong Xiaowu , Guo Yu , Zhang Jingyu , Shen Zheyuan , Wu Shuang , Geng Shuangshuang , Ma Xinna , Hu Miao , Zhou Xinglu 
Published: December 2024

Introduction:
Antibody-drug conjugates (ADCs), as an emerging class of targeted therapies, have garnered significant attention in cancer treatment due to their clinical potential in recent years. Currently, most ADC payloads are cytotoxic agents, prompting the need for novel payloads. Given the catalytic mechanism of action and expanded targeting capabilities, degraders are considered potential candidates for the next-generation payloads. We identified a potent and conjugable GSPT1 degrader CDG0501 through our Rosetta For Molecule Glue (RFMG) model and CRBN-based degrader library. Considering CD123 is a cell surface protein overexpressed in several hematologic malignancies, including AML and myelodysplastic syndrome (MDS), with restricted expression in normal hematopoietic stem cells, CDG0501 was conjugated to a humanized IgG1 targeting CD123 via a tumor-enriched protease-cleavable linker, resulting in HDZ-C123A, a stable and homogeneous conjugate with a drug-to-antibody ratio of 8. After a series of evaluations, HDZ-C123A has been validated as a promising pre-clinical candidate for further clinical development.
Results: CDG0501 showed sub-nanomolar to nanomolar activity against multiple acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL) cell lines. In CD123-expressing cell lines, HDZ-C123A exhibited picomolar proliferative inhibition activity, which was 20-1000 times more potent than several GSPT1 degraders, including CC-90009, and showed robust activity in Mylotarg-resistant cell lines. Ex vivo experiments revealed a stronger potency of HDZ-C123A in AML patient-derived blasts compared to CC-90009 and venetoclax. HDZ-C123A demonstrated minimal toxicity to peripheral blood mononuclear cells derived from healthy subjects, highlighting the potential of conjugation strategies to improve degraders' narrow therapeutic index. HDZ-C123A showed significant anti-tumor efficacy and safety in several hematologic xenograft models and patient-derived models following single-dose administration. Particularly in the MV4-11 xenograft model, complete response was observed at doses as low as 1 mg/kg, Pharmacodynamic studies demonstrated that tumor growth inhibition correlated with the abundance of GSPT1 and related biomarkers.
Conclusions:
In summary, CDG0501, as a potent GSPT1 degrader, demonstrates potential as a next-generation payload in preclinical studies. HDZ-C123A, constructed based on CDG0501, shows promising potential as a first-in-class CD123-targeting degrader-antibody conjugate for AML treatment.
Final Results of a Phase 2, Single Arm Trial Evaluating Letermovir for Cytomegalovirus Prophylaxis in Patients with Hematological Malignancies Treated with Alemtuzumab
Authors: Reneau John C. , Huang Ying , Hanel Walter , Chung Catherine , Brammer Jonathan E. , William Basem 
Published: December 2024

Cytomegalovirus (CMV) reactivation is a common complication in immunocompromised patients, including those treated with alemtuzumab. Letermovir is a potent antiviral approved CMV prophylaxis following allogeneic bone marrow transplantation. This trial aimed to investigate the efficacy of letermovir in preventing CMV reactivation in patients treated with alemtuzumab.
This was a single arm trial that included patients with hematologic malignancies treated with alemtuzumab who were seropositive for prior CMV exposure (IgG positive). Patients began letermovir 480 mg daily within 14 days of starting alemtuzumab and continued through 3 months after the last dose of alemtuzumab. The primary objective was to estimate the rate of CMV reactivation while on letermovir. CMV PCR was performed at least every 2 weeks during the study period.
The trial enrolled six patients. The median age was 74 (56-80) and 50% were male. Four patients (66.7%) had T-cell prolymphocytic leukemia, one patient (16.7%) had Sezary syndrome, and one patient (16.7%) had erythrodermic mycosis fungoides.
None of the patients enrolled experienced CMV reactivation during the study period. The most common adverse events of grade 3 or higher at least possibly attributable to letermovir included thrombocytopenia (50%), leukopenia (33.3%), anemia, diarrhea, prolonged APTT, elevated alkaline phosphatase, lymphopenia, neutropenia, and sinus bradycardia (16.7% each).
The trial was closed prior to completing accrual due to low enrollment, limiting the ability to draw definitive conclusions. Overall, the trial showed that letermovir may be effective in preventing CMV reactivation in patients treated with alemtuzumab. Further research in a larger trial is needed to validate these findings.
Ability of Platelet CREB3L1 mRNA Expression Analysis to Detect Ph-Negative MPNs: Independent Confirmation in Archival Patient Samples
Authors: Stolyar Marina , Olkhovskiy Igor , Gorbenko Aleksey 
Published: December 2024

Background. Previously [1] mRNA of CREB3L1 gene expression level could reliably distinguish Ph-MPN from reactive hypercytosis it was found using RNA-seq analysis and subsequent quantitative RT-PCR in platelet-rich plasma. This reasonably suggests the prospect of creating a single simple test that would avoid the costly diver mutation analysis and bone marrow biopsy in the first step of Ph-MPN diagnosis.
Aims. Evaluate the diagnostic potential of the CREB3L1 mRNA expression in archival cDNA transcriptome samples of platelets from patients examined in our laboratory for suspected MPNs.
Methods. We used frozen at -20°C cDNA samples obtained from platelet RNA of patients examined between March 11 and June 30, 2015. A total of 49 samples from patients with confirmed Ph-MPNs (PV-26, ET-18 and MF-5) were included. Of these, 43 patients had the V617F JAK2 mutation (Me VAF = 33.5%), one patient had a mutation in exon 12 of JAK2 and one patient had a double mutation V617F JAK2 + CALR del. In three patients, driver mutations could not be detected (tri-negative MPN). The comparison group included samples from 47 patients also referred to the laboratory with suspected MPN, but who did not receive confirmation of this diagnosis. Measurement of the CREB3L1 mRNA expression level was performed according to the PCR-RT method described in the article [1] with minimal modifications. The calculation was performed using the ∆Сt method. Statistical analysis was performed using the R program.
Results. In all patients with MPNs, CREB3L1 mRNA expression in platelets was 62.5; 41.4-88.1 (Me;Q25-Q75). No dependence on routine hematological parameters, VAF V617F JAK2 values or clinical variant of MPNs was found in this sample. CREB3L1 mRNA platelets expression in patients with unconfirmed MPN was determined at a minimal level only in 21 patients and was significantly lower - 10.0; 5.8-12.1 (P&lt;0.0001). The remaining patients in this group did not have CREB3L1 mRNA expression.
Summary and Conclusions. The ability of CREB3L1 mRNA expression analysis to identify different variants of Ph-MPNs in a retrospective study was independently confirmed using archival platelet cDNA samples from patients in the Siberian region.
Literature:
1. Morishita S, Yasuda H, Yamawaki S, Kawaji H, Itoh M, Edahiro Y, Imai M, Kogo Y, Tsuneda S, Ohsaka A, Hayashizaki Y, Ito M, Araki M, Komatsu N. CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome-negative myeloproliferative neoplasms. Cancer Sci. 2021;112(2):884-892. doi: 10.1111/cas.14763.
Safety and Efficacy of Dara-Based Regimen Followed with ASCT in Transplant-Eligible, Newly-Diagnosed Systemic Light Chain Amyloidosis
Authors: Le Can , Li Juan 
Published: December 2024

Objectives:Daratumumab in combination with cyclophosphamide, bortezomib (Dara-VCd), and dexamethasone is the currently standard frontline therapy for newly-diagnosed AL amyloidosis. However, up to one-fourth of patients do not achieve a deep response (≥VGPR) with D-VCd induction. ASCT can upgrade hematologic responses in patients with suboptimal response to Dara-VCd. This study will assess the efficacy and safety of Dara-based induction therapy followed with ASCT consolidation in AL amyloidosis.
Methods:This was a retrospective analysis comparing VD induction followed by ASCT (VD+ASCT) with Dara-based induction followed by ASCT (Dara-based +ASCT) in the treatment of patients with newly diagnosed AL amyloidosis. The median induction cycles were 4.
Results:A total of 22 patients with AL amyloidosis were included in the analysis between 03/2011 and 12/2023 in our center. Among these patients,16 patients were in VD+ASCT group and 6 patients were in Dara-based +ASCT group. The median age at diagnosis was 52.5(46.3-57) in VD+ASCT group and 59(54.5-62.3) in Dara-based +ASCT group. At diagnosis,73.3% (11/15) had Mayo 2004 stage I in VD+ASCT group, with 66.7% (4/6) having Mayo 04 stage I in Dara-based +ASCT group. There were 100% kidney involvement in both groups. At the end of induction therapy, the rate of hematologic CR was 37.5% (6/16) in VD+ASCT,66.7% in Dara-based +ASCT (P=0.348). Five of the sixteen patients (31.3%) with renal involvement achieved a renal response in VD+ASCT group, with 3 of the six patients (50%) in Dara-based +ASCT group(P=0.624) after induction therapy. The best hematologic response after ASCT was CR in 9(56.3%) patients treated with VD+ASCT, in 5(83.3%) patients with Dara-based +ASCT. Six of the sixteen patients (37.5%) achieved a renal response in VD+ASCT group, with 5 of the six patients (83.3%) in Dara-based +ASCT group after induction therapy. TRM in two groups were 0.
Conclusions:Dara-based regimen followed with ASCT is safe and can upgrade hematologic responses in carefully selected patients with newly-diagnosed AL amyloidosis.
Utilizing BTK Inhibitors for Maintenance and Long-Term Control Following CAR-T Cell Therapy in B-Cell Non-Hodgkin Lymphoma
Authors: Liu Rui , Yang Fan , Ma Lixia , Guo Yuelu , Fu Zhonghua , Deng Biping , Zheng Qinlong , Ke Xiaoyan , Hu Kai 
Published: December 2024

Background:
Following chimeric antigen receptor (CAR)-T cell therapy, achieving long-term durability in approximately 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) cases remains a significant challenge. There is ongoing consideration that BTK inhibitors may serve as a potential option for maintenance therapy in these patients.
Methods:
A retrospective analysis was conducted on patients who were evaluated as remission (complete remission or partial remission) 3 months after CD19-CAR-T treatment, and were treated with BTKi maintenance therapy to observe the progression-free survival and overall survival of the patients.
Results:
From December 2019 to March 2024, a total of 37 patients were included in the study, with diagnoses comprising CNS lymphoma (14/37), CLL/Richter (5/37), MCL (2/37), DLBCL (14/37), and tFL (3/37). Of these patients, 43% (16/37) were male, with a median age of 52 years (range 21-74). Among them, 23 patients received zanubrutinib, while 14 received either Orelabrutinib or ibrutinib. NGS testing was conducted in 24 patients, revealing MYD88 and/or CD79B mutations in 8/24 cases. Median maintenance duration was 510 days (range 90-1370). Median follow-up time was 30.61 months, with only 2 patients experiencing relapse and 3 deaths recorded. Median progression-free survival (PFS) and overall survival (OS) were not reached. Comparing patients with and without MYD88/CD79B mutations, the 3-year PFS rates were 85.7% vs. 70% (p=0.375). Patients eligible for BTK inhibitors (CNS involvement, chronic lymphocytic leukemia, mantle cell lymphoma) compared to others(DLBCL and tFL) had 3-year PFS rates of 78.3% and 90% (p=0.230), respectively.
Conclusion:
BTK inhibitors could serve as maintenance therapy for patients achieving remission with B-NHL CAR-T within three months, with potentially greater benefits observed in those with the MCD genetic subtype.
Efficacy and Safety of Mosunetuzumab in Relapsed/Refractory Non-Hodgkin Lymphoma: A Systematic Review
Authors: Elemian Shatha , Habbas Ahmad , Jumean Samer , Al Omour Bader , Hamad Munther , Tan Jia Yi , Chan Kok Hoe , Guron Gunwant , Shaaban Hamid 
Published: December 2024

Background:
Bispecific antibodies (BsAbs) represent a promising new class of immunotherapy for lymphoma treatment. mosunetuzumab, a CD20xCD3 T-cell engaging bispecific monoclonal antibody, directs T cells to eliminate malignant B cells. It was the first to receive approval for relapsed or refractory follicular lymphoma. This study evaluates the safety and efficacy of intravenous mosunetuzumab in various treatment regimens for relapsed/refractory non-Hodgkin lymphoma.
Methods:
A systematic literature search was conducted on PubMed using keywords “Mosunetuzumab” AND “lymphoma” from inception to January 1, 2024. Four non-randomized clinical trials (nRCTs, N=303) were identified and included in accordance with PRISMA guidelines.
Results:
In 4 clinical trials 303 patients were concluded, of which 186 patients were diagnosed with diffuse large B-cell lymphoma (DLBCL), and 117 patients were diagnosed with follicular lymphoma (FL), 98 patients with DLBL received mosunetuzumab plus polatuzumab vedotin, 80 patients with DLBCL received mosunetuzumab monotherapy, 90 patients with FL were treated with mosunetuzumab monotherapy, and 27 patients with FL received mosunetuzumab in combination with lenalidomide. 186 patients had diffuse large B-cell lymphoma (DLBCL), and 117 patients had follicular lymphoma. overall response rate (ORR), complete response (CR), and partial response (PR) were reported in 42%, 24%, 18% patients with DLBCL who received intravenous mosunetuzumab monotherapy respectively. ORR, CR, and PR were reported in 59%, 46% and 13% patients with DLCBL receiving mosunetuzumab plus polatuzumab vedotin. ORR, CR, and PR were reported in 72% 54% and 18% patients, respectively, treated with intravenous mosunetuzumab monotherapy in follicular lymphoma. ORR, CR, and PR were reported in 92%, 77% and 15% patients, respectively, treated with combination with lenalidomide in follicular lymphoma. Cytokine release syndrome (CRS) was the most common side effect occurred at any grade, neutropenia was the most common reported grade ≥3 followed by CRS, grade 3 or more of immune cell-associated neurotoxicity syndrome was limited.
Conclusions:
Mosunetuzumab in combination with lenalidomide demonstrated higher efficacy and good tolerability in patients with relapsed/refractory non-Hodgkin lymphoma, especially in achieving high response rates inFL. Intravenous mosunetuzumab monotherapy was active in both DLBCL and FL with low rates of toxicity and favorable safety profile. Long-term follow-up is necessary to assess durability of responses and overall safety and survival outcomes with these different treatment approaches.