bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pola-R-CHP Regimen Exhibited a High Response Rate and Good Treatment Tolerability for Newly Diagnosed Double-Expressor Lymphoma
Authors: Zhao Xia , Liu Zhihe 
Published: December 2024

Background:
Double-expressor lymphoma (DEL) is characterized by the overexpression of C-MYC and BCL2 proteins without underlying chromosomal rearrangements. Although it is not classified as a distinct entity in the current World Health Organization classification, DEL accounts for 20% to 30% of diffuse large B-cell lymphoma (DLBCL) patients. Currently, the prognosis for DEL patients remains poor despite receiving R-CHOP or R-EPOCH regimens as first-line chemotherapy.
Aims:
This study aimed to assess the clinical efficacy and treatment tolerance of the Pola-R-CHP regimen in DEL patients.
Methods:
In this study, newly diagnosed DEL patients were recruited from our hospital in China between June 2023 and April 2024. The cut-off values for C-MYC and BCL2 protein expression were defined as greater than 40% and 50%, respectively. Clinical information, overall response rates, and adverse events of all patients were collected. The Pola-R-CHP regimen consisted of polatuzumab vedotin (1.8 mg per kilogram of body weight), plus intravenous rituximab (375 mg per square meter), cyclophosphamide (750 mg per square meter), liposomal doxorubicin (30 mg per square meter) on day 1 of each cycle, and oral prednisone (100 mg once daily) on days 1 through 5 of the first six cycles.
Results:
Twenty-three newly diagnosed DEL patients were enrolled, with a median age of 68 years (range 37-79 years). The male-to-female ratio was 11:12. According to the Ann Arbor stage, 78.3% of patients were in stages III/IV, and 52.2% had an International Prognostic Index (IPI) score ≥3. Additionally, 69.6% had at least two extranodal lesions, commonly involving the spleen, gastrointestinal tract, kidneys, adrenal glands, uterus, and ovaries. White blood cell count, hemoglobin, and platelet levels were generally normal. Elevated levels of lactic dehydrogenase and β2 microglobulin were observed in 60.9% and 65.2% of patients, respectively. Based on Hans's algorithm, 82.6% of patients were classified as non-GCB. The median Ki-67 value was 80% (range 60%-95%), and three patients were CD5 positive. P53 protein expression greater than 50% was observed in 69.6% of patients. All patients completed at least three cycles of the Pola-R-CHP regimen. The overall response rate (ORR) was 91.3%, with a complete response rate (CRR) of 47.8% at the end of the third cycle. By the end of treatment, the ORR was 83.3%, and the CRR was 72.2%. The common adverse events of this Pola-R-CHP regimen were hematologic toxicities, and 43.5% of patients exhibited grade 3/4 granulocytopenia after three cycles.
Conclusion:
The Pola-R-CHP regimen demonstrated high response rates and good tolerability in patients with DEL, establishing it as an effective therapeutic option.
Pola-R-CHP Regimen for Frontline Therapy in Diffuse Large B Cell Lymphoma with High-Risk Factors
Authors: Zhao Xia , Liu Zhihe 
Published: December 2024

Background:
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of malignant tumors. Currently, the first-line R-CHOP chemotherapy regimen can cure approximately 60% of DLBCL patients, but about 40% still experience refractory or relapses. Further studies have found that patients with refractory or relapses often present with high-risk factors at initial diagnosis, such as high international prognostic index (IPI), extranodal involvement, double-expressor lymphoma (DEL), and double-hit lymphoma.
Aims:
This study aimed to evaluate the clinical efficacy and treatment tolerance of the Pola-R-CHP regimen for DLBCL patients with high-risk factors.
Methods:
We enrolled newly diagnosed DLBCL patients with high-risk factors who were treated with Pola-R-CHP as the first-line regimen at our hospital in China between April 2023 and May 2024. In this study, high-risk factors included an IPI &gt;2, DEL, P53 protein overexpression (&gt;50%), and extranodal involvement &gt;2 at diagnosis. We collected clinical information, overall response rates, and adverse events for all patients. The Pola-R-CHP regimen included polatuzumab vedotin (1.8 mg/kg), rituximab (375 mg/m²), cyclophosphamide (750 mg/m²), liposomal doxorubicin (30 mg/m²) on day 1 of each cycle, and prednisone (100 mg orally, once daily) on days 1 through 5 of each of the first six cycles.
Results:
Forty-seven newly diagnosed DLBCL patients with high-risk factors were eventually enrolled, with a median age of 68 years (range 33-79). The male-to-female ratio was 1.1:1.0. Based on the Ann Arbor staging system, 78.7% of patients were classified as stage III/IV, and 61.7% had an IPI &gt;2. Additionally, 48.9% of patients had at least three extranodal lesions, with the spleen, gastrointestinal tract, kidneys, adrenal glands, and bone marrow, being the most commonly involved organs. Furthermore, 66.0% of patients had B symptoms. White blood cell count, hemoglobin, and platelet count were nearly normal across all patients, while high levels of lactic dehydrogenase and β2 microglobulin were found in 63.8% and 61.7% of patients, respectively. According to the Hans algorithm, 76.6% of patients were in the non-GCB group, and the median Ki-67 value was 80% (range 60%-95%). Five patients were CD5 positive, and 48.9% were diagnosed with DEL. Among the cohort, 53.2% of patients exhibited expression greater than 50%. All patients completed at least three cycles of the Pola-R-CHP regimen. The overall response rate (ORR) was 93.6%, with a complete response rate (CRR) of 48.9% at the end of the third cycle. By the end of treatment, the ORR was 89.7%, and the CRR was 76.9%. The most common adverse events were hematologic toxicities, with 36.1% of patients experiencing grade 3/4 granulocytopenia after three cycles.
Conclusion: The Pola-R-CHP regimen showed high response rates and good tolerability in DLBCL patients with high-risk factors, proving it to be an effective therapeutic option.
T(11;14) with Multiple Myeloma: Standard Risk Survival but Slow and Poor Response
Authors: Liu Yuntong , Qiu Lu-Gui , An Gang 
Published: December 2024

Introduction:
Presence of t(11;14) on plasma cells is considered a standard-risk prognostic factor per IMWG risk-stratification. However, recent studies suggest inferior PFS and OS observed among t(11;14) patients relative to the standard-risk myeloma patients.
Methods:
This study aimed to evaluate the impact of t(11;14) in newly diagnosed multiple myeloma (NDMM) patients on treatment response rate, response kinetics, and survival based on mutually exclusive risk groups. We describe 790 patients with newly diagnosed myeloma treated with available baseline FISH data (within 90 days post-diagnosis) from January 2010 until June 2021, including 99 patients with t(11;14) alone, 58 with t(11;14) plus other high-risk cytogenetic abnormalities [t(11;14)+HR] including chromosome 1 abnormalities [C1A1, including gain/amp1q and/or del(1p)] and/or del(17p), 224 standard-risk (SR) patients without t(11;14) and 409 in the high-risk cytogenetic abnormality (HRCA) group including t(4;14), t(14;16), t(14;20), C1A1 and/or del(17p) but without t(11;14).
Results:
Our study have showed NDMM patients in the t(11;14)alone group had similar PFS (49.3 vs. 50.7 months; P= 0.392) and OS (112.4 vs. NR months; P= 0.982) as those in the SR patients, but had a significantly worse response than the SR group (t(11;14)alone vs. SR: ≥VGPR 72.9% vs. 85.2%, P= 0.011; ≥CR 50.0% vs. 66.8%, P= 0.005; MRD- 60.0% vs. 76.0%, P=0.009). Paradoxically, depth of response does not seem to be significantly associated with better survival in the t(11;14)alone group (PFS: &lt; VGPR vs. CR, P=0.235, MRD- vs. MRD+, P= 0.159; OS: &lt;VGPR vs. CR, P=0.256, MRD- vs. MRD+: P= 0.082). Response kinetics analyses showed that the t(11;14)alone group had a significantly slower time to response than the other subgroups (t(11;14)alone vs. SR vs. HRCA: median time to VGPR=4.93 vs. 3.01 vs. 2.63 months; P&lt; 0.05; median time to MRD negativity= 9.19 vs. 4.25 vs. 4.27 months; P&lt;0.001).
Conclusion:
The slow rate of response may explain the paradoxical relationship between poorer depth of response and standard risk survival outcomes, suggesting the need for individualised therapeutic strategies for this group of patients. On the other hand, t(11;14) coexistence does not provide a survival benefit for high-risk genetic patients. Patients with t(11;14) plus other high risk cytogenetic abnormalities requires early and more aggressive treatment options, such as BCL-2 inhibitors.
Caplacizumab in the Treatment of Thrombotic Thrombocytopenic Purpura: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Khan Salman , Karmani Vikash Kumar , Ali Aizaz , Khan Malik W.Z. , Ahmad Muhammad , Niazi Muhammad , Qandil Hamzah , Yetiskul Ekrem , Khamis Zaid , Araji Ghada , Sarkis Tyler , Mohan Preet , Afif Sarah 
Published: December 2024

Introduction: Thrombotic Thrombocytopenic Purpura (TTP) is an uncommon thrombotic disorder characterized by the formation of platelet-rich microthrombi due to a reduction in ADAMTS13 levels. Caplacizumab has surfaced as a viable therapeutic alternative. Consequently, we conducted a thorough review and meta-analysis to evaluate caplacizumab in the management of TTP.
Method: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching PubMed, Google Scholar, and Cochrane CENTRAL databases from inception to December 2023. The evaluated outcomes included Time to normalization of platelet count, Days of Plasma Exchange, Length of Hospitalization, Relapses, Exacerbations, and Refractory Disease. Additionally, we included patients who had undergone at least one therapeutic plasma exchange. The Review Manager software was utilized to perform the meta-analysis, wherein risk ratios (RR) were calculated, 95% confidence intervals were ascertained, and statistical significance was established as a p-value &lt;0.05. The presence of variation between studies was evaluated using X2 tests and I2 statistics.
Results: We screened 4064 articles and included 7 observational studies (925 patients). Our meta-analysis indicated that TTP patients treated with caplacizumab achieved a statistically insignificant reduction in the duration needed to achieve normal platelet counts (RR= 0.70; 95% CI= 0.44 - 1.14), number of days of plasma exchange (RR= 0.69; 95% CI= 0.36 - 1.32), length of hospitalization (RR= 0.84, 95% CI = 0.53 - 1.34), refractory disease (RR= 0.48, 95% CI= 0.19 - 1.17), and exacerbations (RR= 0.33, 95% CI= 0.09 - 1.14). However, there was an insignificant rise in the relapse rate (RR= 1.03; 95% CI= 0.38 - 2.80) as compared to the control group.
Conclusion: In summary, our study demonstrates that adding caplacizumab to standard TTP therapy significantly reduces the time to achieve normal platelet counts, shortens the duration of plasma exchange, minimizes hospitalization, and lowers the rates of refractory disease and exacerbations. These findings highlight the effectiveness of caplacizumab in improving key clinical outcomes for TTP patients.
Keywords: Caplacizumab; Meta-analysis; Platelet count; Relapse; Thrombotic Thrombocytopenic Purpura
Tislelizumab in Combination with Chidamide, Prednisone, Etoposide, and Lenalidomide Followed By Autologous Stem Cell Transplant in Patients with Relapsed or Refractory Hodgkin Lymphoma
Authors: Wang Yawen , Xue Hongwei 
Published: December 2024

Background
Approximately 10% to 30% of Hodgkin lymphoma (HL) patients suffer primary refractory or disease relapse (R/R). Our objective is to assess the efficacy and safety of tislelizumab in combination with chidamide, prednisone, etoposide, and lenalidomide (T-CPEL) as an introductory treatment following autologous hematopoietic stem cell transplantation (ASCT) or tislelizumab combined with bendamustine (TB) as consolidation in R/R HL.
Methods
Patients with R/R classic HL (cHL) who received T-CPEL regimen were included in our retrospective cohort study.
Results
Between January 2020 and December 2022, a total of 11 patients with R/R cHL were enrolled in our project. The average number of previous systemic therapies was 2 (range 1-6). All patients received at least four cycles of the T-CPEL regimen as an introductory treatment. There was an overall response rate (ORR) of 90.9%, with a complete remission (CR) rate of 36.4%. Five eligible patients underwent ASCT after receiving TB, while six ineligible patients only received TB consolidation therapy. The median follow-up was 21.6 months, and the expected three-year progression free survival (PFS) and overall survival (OS) rate were estimated to be 81.8% and 100.0%, respectively. During the introduction regimen of T-CPEL, 14 adverse events were recorded, most of which were grade one or grade two. No treatment-related deaths or discontinuation occurred.
Conclusion
The salvage therapy consisting of tislelizumab plus CPEL demonstrated both effectiveness and tolerability in treating R/R cHL cases. Furthermore, following ASCT or TB therapy, there was an increased likelihood for achieving a cure.
Efficacy and Safety of Prophylactic Use of Peg-Rhg-CSF before CAR-T Cell Infusion in MM Patients
Authors: Xu Jintao , Guo Dan , Hong Lemin , Lu Jinfeng , Li Bingzong , Hongming Huang 
Published: December 2024

Background:Infection caused by leukopenia is an important complication of CAR-T cell therapy, and there is no unified consensus on the use of CSF during CAR-T therapy. It is not clear whether the prophylactic use of PEG-rhG-CSF can alleviate leukopenia and reduce the chance of infection, or whether it may increase the risk of CRS and ICANS.
Aims:We explore the efficacy and safety of prophylactic use of PEG-rhG-CSF before CAR-T cell reinfusion in MM patients, in order to provide some data support for the application of PEG-rhG-CSF in CAR-T cell therapy.
Methods:We studied 30 patients with MM who received anti-BCMA CAR-T cell or anti-BCMA and CD19 CAR-T cell therapy (ChiCTR2000033567). Patients received FC pretreatment from days -4 to -1 and were infused with 1-2*106/Kg CAR-T cells. Among them, 11 patients received PEG-rhG-CSF 3-6 mg on day 0, and 19 patients did not receive PEG-rhG-CSF. The response status, incidence of CRS and ICANS, incidence and duration of neutropenia and agranulocytosis, and antibiotic use of the two groups were analyzed.
Results:There was no significant difference in the remission rate above VGPR within 3 months after reinfusion between the PEG group and the non-PEG group (72.73% vs. 78.95%, p=1.000). The incidence of CRS in the two groups was 1 case in stage I, 1 case in stage II, 1 case in stage III, and 1 case in stage IV in the PEG group, and 2 cases in stage II and 1 case in stage IV in the non-PEG group. ICANS occurred in 1 case in each group. There was also no significant difference in the incidence of neutropenia (90.91% vs.100%, p=0.367). The incidence of agranulocytosis in PEG group was significantly reduced (27.27% vs. 73.68%, p=0.023), and the duration of agranulocytosis was significantly shorter than that in the control group (mean 1.36 vs. 5.89, p=0.013). There was no significant difference in the antibiotic usage rate (63.64% vs. 73.68%, p=0.687), which included preventive drugs such as SMZ-CO and acyclovir.
Conclusion:This study showed that the prophylactic use of PEG rhG CSF in MM patients before CAR-T cell therapy could shorten the degree and duration of neutropenia without aggravating the occurrence of CRS, and reduce the risk of severe infection. This provides certain data support for guiding the application of PEG-rhG-CSF in CAR-T cell therapy for MM patients.
Transcriptomic Analysis Shows a Common Multi-Organ Inflammatory/Complement Signature in Hemolysis-Induced Damage
Authors: Peliconi Julie , Lavergne Julien , Brochier Camille , Guinot Florent , David Tovo , Roumenina Lubka T , Grunenwald Anne 
Published: December 2024

Introduction: Intravascular hemolysis is a major contributor to tissue injury in transfusion reactions, hemoglobinopathies such as sickle cell disease (SCD) and hemolytic anemias. The release of hemoglobin and heme, usually confined to red blood cells, leads to oxidative stress, endothelial activation, and a prothrombotic and pro-inflammatory phenotype. Nevertheless, the underlying mechanism is not fully understood.
Methods: To understand the organ injury in hemolytic conditions, we used RNAseq to explore the transcriptomic changes of lung, spleen, liver and kidney in a mouse model of hemolytic crisis triggered by phenylhydrazine injection. We analyzed immune cell influx by MCP counter and the impacted biological pathways by Gene Set Enrichment Analysis (GSEA). As complement was one of the common enriched pathways in all tested organs of the hemolytic mice accompanied by C5a elevation in plasma, we expressed and validated a recombinant version of the mouse C5 inhibiting antibody BB5.1 and tested it in the mouse model. The transcriptional response to complement inhibition was assessed by Quantigene (80-gene plex).
Results: Phenylhydrazine-induced hemolysis caused dysregulation of the renal (165 DEG, differentially expressed genes), pulmonary (521), hepatic (704) and splenic (1696) transcriptomes. GSEA analysis revealed an enrichment of gene sets linked to xenobiotic metabolism, reflecting heme degradation, cell death, cell cycle arrest, metabolic reprogramming and inflammatory pathways related to TNFa, IL6 and IL2, as well as the complement system. Indeed, C5a plasma levels in phenylhydrazine-treated mice were increased. Inhibition of C5 with BB5.1 (1g/mouse) reduced C5a release and attenuated the inflammatory response to hemolysis, particularly in the lung.
Conclusion: Here we provide the first transcriptomic signature atlas of mouse organs with intravascular hemolysis, underpinning a key role of inflammation, oxidative stress and metabolic reprogramming and complement activation. These findings support further exploration of complement-targeted therapies to ameliorate hemolysis and preserve organ function in SCD patients.
Immune Reconstitution Following Allogeneic HSCT in Hematological Diseases
Authors: Naseeb Summaira , Ahmed Parvez , Nasir Shahzad , Zahur Umar , Mahmood Syed Karman , Chaudhry Brig Qamar Un N , Ur Rahman Khalil , Peter Hina , Fatima Mehroz 
Published: December 2024

Objective: To evaluate immune reconstitution following allogeneic hematopoietic stem cell transplantation
Study Design: Retrospective cohort study
Place and Duration of the Study: Department of Bone Marrow Transplant, Quaid-e-Azam International Hospital Islamabad, Pakistan; from January 2023 to January 2024.
Methodology: We evaluated 50 adult and pediatric patients undergoing allogeneic HSCT for malignant and nonmalignant diseases from year 2022 to 2023. Absolute lymphocyte count, lymphocyte subsets and immunoglobulin levels were performed at 6 and 12 months post-transplant. Patients who did not have complete medical records or faced graft failure/rejection before 6 months post-transplant were excluded from the study.
Results:
In our study absolute lymphocyte count recovery was observed in 94% of patients on D+180 that increased to 100% on D+365. The average number of cells being 2599.84/μL (SD=1281.742) and 2926.96 μL (SD=1065.378) on D+180 and D+365 respectively. By day 180 post-transplant, 84% of patients had achieved CD3+CD8+ recovery, while CD16+CD56+ and CD19+ cell recovery was seen in 74% and 56% cases respectively. Day +180 CD3+CD4+ recovery was seen in only 8% patients that increased to 21% by day +365. Normal lymphocyte recovery values at day 365 post-transplant were: CD3+CD8+ in 84% patients, CD16+CD56+ and CD19+ cells in 78% patients. Early CD3+CD4+ recovery was seen in patients with age &lt;18 years, non-malignant diseases and with no or minimal GVHD but the values were not statistically significant. Age adjusted normal immunoglobulin levels for IgG, IgM and IgA by day +180 were achieved in 92%, 90% and 84% patients while after 1 year 98%, 90% and 96% patients had normal levels of IgG, IgM and IgA respectively. Patients receiving CD34+ dose &gt;5 x 106/kg had significantly early neutrophil engraftment (p=0.025); mean 11.40 days (SD 1.67) versus 13.76 days (SD 1.43) for CD34 dose ≤ 5 x 106/kg.
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Conclusion: Majority of the patients achieved normal immunoglobulin levels and lymphocyte subsets by day 180 post HSCT while CD3+CD8+ T cell recovery was seen in 8% and 21% patient by day 180 and 365 post-transplant, respectively.
Key Words: Hematopoietic stem cell transplant, lymphocyte subsets, immune reconstitution
Safety and Efficacy of Allogeneic NKG2D NKR-NK for Acute Myeloid Leukemia
Authors: Zhou Li , Shen Haihao , Fang Fang , Zhang Ming , Hu Zuhong , Wu Congmiao , Tao Qianshan , Li Yingwei , Wu Fan , Pan Ying , Wang Zhitao , Xiao Weihua , Zhai Zhimin 
Published: December 2024

Objective: CAR-T cells have shown significant clinical efficacy in treating acute lymphoblastic leukemia, but their effectiveness in treating patients with acute myeloid leukemia (AML) is limited, necessitating the exploration of alternative treatments. Theoretically, compared to CAR-T cells, CAR-NK cells possess more favorable toxicity profiles, particularly in mitigating adverse effects such as cytokine release syndrome and graft-versus-host disease. However, issues regarding the in vivo proliferation and long-term survival of CAR-NK cells remain unresolved, typically requiring large-dose infusions. Our study tested the safety of infusing high-dose NKG2D NKR-NK cells into AML patients.
Methods: NK cells from healthy donors were transduced into NKG2D NKR-NK cells and expanded in vitro. The cytotoxicity of NKG2D NKR-NK cells against peripheral blood progenitor cells from AML patients was validated in vitro. The safety and antitumor efficacy were further confirmed in severely immunodeficient NCG mice and in xenograft AML mouse models. Additionally, NKG2D NKR-NK cells were intravenously infused into clinical trial participants to observe their in vivo antitumor activity and safety, using a dose-escalation approach to determine the maximum safe dose.
Results: NKG2D NKR-NK cells exhibited high cytotoxicity against AML-targeted cells in vitro (90% killing rate for K562 cells, 60% for HL-60 cells, and 8% for KG-1 cells). In the xenograft AML mouse model, NKG2D NKR-NK cells significantly reduced tumor burden, demonstrating strong antitumor effects. Intravenous infusion of NKG2D NKR-NK cells into AML patients did not result in any observable severe adverse effects, confirming the safety of NKG2D NKR-NK cells in the treatment of four patients at the current maximum single dose of 3.1×109 cells.
Conclusion: Our data indicate that NKG2D NKR-NK cells are effective and safe in vitro and in mouse models, and are safe in four AML patients.