Mohamed A. Kharfan-Dabaja's research while affiliated with Mayo Clinic and other places
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Publications (689)
We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peri...
7038
Background: While chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment for hematological malignancies, severe (≥ grade 3,Gr 3, CTCAE) cytopenias post CAR-T and therapy related myeloid neoplasms (t-MN) are particularly difficult to manage. Survival after diagnosis of t-MN is dismal. Management of ≥Gr 3 cytopenias that do n...
This cohort study examines the role of comprehensive bridging radiotherapy in the setting of chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma.
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting the use of axi-cel in patients with LBCL, outcomes stratified by race and ethnicity groups are limited. Here, we report clinic...
Background
One major limitation for broader applicability of allogeneic hematopoietic cell transplantation (allo-HCT) in the past was the lack of HLA-matched histocompatible donors. Preclinical mouse studies using T-cell depleted haploidentical grafts led to an increased interest in the use of ex vivo T-cell depleted (TCD) haploidentical allo-HCT....
Chimeric antigen receptor (CAR) T-cell therapy has encountered limited success in solid tumors. The lack of dependable antigens and the immunosuppressive tumor microenvironment (TME) are major challenges. Within the TME, tumor cells along with immunosuppressive cells employ an immune-evasion mechanism that upregulates programmed death ligand 1 (PD-...
Background Although CAR T-cell therapy has achieved remarkable response in patients (pts) with B-cell non-Hodgkin’s lymphoma (NHL), 20-30% of pts still have primary refractory disease (PD1), and another 30-40% relapse (PD2). We and others have shown that monocytes can modulate T-cell functions and impact clinical response to chemoimmunotherapy in N...
Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is an established treatment modality for the management of refractory and/or relapsed non-Hodgkin lymphoma (NHL). Despite restrictions on granulocyte colony-stimulating factor (G-CSF) use in registration clinical trials due to potential worsening of cytokine release syndrome (CRS), G-CS...
Diffuse large B cell lymphoma (DLBCL) is one of the most prevalent subtypes of non-Hodgkin lymphoma (NHL) and is known for commonly infiltrating extra-nodal sites. The involvement of the bone marrow by lymphoma cells significantly impacts the staging, treatment, and prognosis among the extra-nodal sites in DLBCL. Bone marrow biopsy has been conside...
Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable of curing these diseases. Allo-HCT has been also shown to be curative in benign hematologic disorders such as aplastic anemia, sickle cell disease, and thalassemia, among ot...
This case-control study examines the incidence and risks of myeloid neoplasms in adults treated for B-cell lymphoproliferative disorders or multiple myeloma.
Chimeric antigen receptor T-cell (CAR-T) therapy is the new standard of care in fit patients with refractory or early relapsed diffuse large B-cell lymphoma (DLBCL). However, there may still be a role for salvage chemotherapy (ST) and autologous stem cell transplant (ASCT) in certain circumstances (eg, lack of CAR-T resources, chemosensitive relaps...
In recent years, chimeric antigen receptor T-cell therapy (CAR T) has revolutionized the treatment landscape for large B cell lymphoma (LBCL), demonstrating remarkable efficacy and ushering a new era of therapeutic possibilities. However, a subset of patients may not achieve the desired response with CAR T. This review examines strategies aimed at...
Introduction
Secondary central nervous system (CNS) involvement develops in 2-10% of large B-cell lymphoma (LBCL) cases. Current treatment approaches for relapsed or refractory CNS disease generally do not provide durable responses. Limited data suggest efficacy and feasibility of CAR-T therapy in SCNSL. We report here the largest multicenter retro...
Introduction: Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of non-Hodgkin lymphoma (NHL). Despite having an increased risk of NHL, patients with pre-existing autoimmune disease (AID) were excluded from pivotal CAR-T trials due to concerns that CAR-T may exacerbate AID. As a result, there are limited data on the...
Introduction:
NGS is increasingly being utilized to identify pathogenic somatic and targetable variants in patients with newly diagnosed AML and MDS. Patients with high-risk disease are typically recommended to undergo allo-HCT as consolidation, upon achieving morphological complete remission (CR). But, despite achieving hematologic CR, patients of...
Introduction: CAR-T therapy is the standard of care for pts with relapsed LBCL as early as in the second line in those with early relapse or with primary refractory disease. In practice, pts who are intended to receive CAR-T, commonly require interim therapy before leukapheresis, wherein a small fraction may achieve a complete remission (CR). Havin...
Purpose
The predominant pattern of relapse for patients with B-cell non-Hodgkin lymphoma (NHL) who undergo anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) involves sites previously involved by NHL. Bridging radiotherapy (BRT) has shown to be an effective bridging treatment with excellent local control rates. Our previous work defined limi...
While acknowledging that newer therapies have improved survival rates in chronic lymphocytic leukemia (CLL), patients with high-risk disease features are at an increased risk of treatment failure. Allogeneic hematopoietic cell transplantation (allo-HCT) was traditionally offered as front-line consolidation in high-risk CLL; however, with the emerge...
Introduction: In Cohorts 1+2 of the ZUMA-1 Phase 1/2 study of axi-cel in R/R LBCL, 11% and 31% of patients (pts) experienced Grade ≥3 cytokine release syndrome (CRS) or neurologic evenets), respectively. To minimize the toxicities seen with axi-cel, a safety management cohort, Cohort 6 (N=40), was added to evaluate whether prophylactic (ppx) cortic...
Background: Ph-like ALL is a high-risk subset of B-lineage ALL that responds poorly to standard chemotherapy regimens. While allogeneic hematopoietic cell transplantation (HCT) is routinely recommended for patients with Ph-like ALL, large multicenter data addressing its role is limited. Here, we conducted a multicenter study to evaluate the role of...
Introduction
Atrial fibrillation/flutter (Afib) contributes independently to the hematopoietic cell transplant comorbidity index (HCTCI) and is a known complication of allogeneic hematopoietic transplantation (AlloHCT) which has been linked to inferior outcomes, particularly in older patients. An electrocardiogram (ECG)-based artificial intelligenc...
Background: The new standard of care for fit patients with refractory or early relapse of diffuse large B-cell lymphoma (DLBCL) is chimeric antigen receptor T-cell (CAR-T) therapy. However, for patients with a relapse ≥12 months after completing frontline therapy, salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell tran...
Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients w...
Anti‐CD19 chimeric antigen receptor T‐cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B‐cell non‐Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a si...
Several CD19-targeting CAR-T cells are used to treat leukemias and lymphomas; however, relapsed and/or refractory (R/R) disease is still observed in a significant number of patients. Additionally, the success of CD19-CAR-T cell therapies is not uniform across hematological malignancies, particularly in chronic lymphocytic leukemia (CLL). In this st...
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with standard conventional chemotherapy. Small observational studies have shown that allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We conducted an analysi...
Autologous stem cell transplant (ASCT) is a standard-of-care treatment for patients with multiple myeloma (MM). However, only 20%-30% of patients with MM for whom the procedure is indicated undergo ASCT. Barriers to ASCT may be informational, financial, logistic, or cultural and may affect patients and/or treating oncologists. The availability and...
Anti-HLA donor specific antibodies have been extensively documented for their critical role in kidney transplant rejection and resulting adverse outcomes. Several approaches have been employed to desensitize these patients; however, none of these explored therapeutic approaches has exhibited enduring clinical benefits. In this study, we explore a n...
We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1T...
The immune system plays a major role in preventing infections and cancers. Impairment in immunity may facilitate the development of neoplasia owing to defective immune surveillance, among other mechanisms. Immune evasion plays a significant role in relapse after allogeneic hematopoietic cell transplantation (alloHCT); one purported mechanism is thr...
Due to the advent of effective novel therapies for multiple myeloma (MM), the use of cryopreserved autologous peripheral blood hematopoietic cells (APBHC) for a salvage autologous transplant (auto-HCT) is in decline. We evaluated utilization trends and costs associated with cryopreserved APBHC in patients with MM. We retrospectively evaluated the c...
Autologous hematopoietic cell transplantation (auto-HCT) has long remained the standard approach for patients with relapsed/refractory (R/R) chemosensitive diffuse large B-cell lymphoma (DLBCL). However, the advent of chimeric antigen receptor (CAR) T-cell therapy has caused a paradigm shift in the management of R/R DLBCL patients, especially with...
Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2-3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cel...
Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CART) on day+30 progress and only 30% achieve spontaneous complete response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual FDG activity on day+30 post-CART in NHL. We re...
Background:
Multiple myeloma (MM) is the second most common hematologic malignancy, with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) remains a standard treatment for MM even in the era of novel therapies. This is usually performed in hospital-based settings, either in t...
e19501
Background: Relapsed and/or refractory (R/R) disease is observed in patients who receive CD19 targeting chimeric antigen receptor (CAR)-T cells to treat B-cell lymphoid leukemias and lymphomas. We generated a novel CAR, MC10029 that targets B-cell activating factor receptor (BAFF-R) to address this unmet medical need. Methods: We engineered...
We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥ 3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1...
To develop a prognostic model for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) for myelofibrosis (MF). We examined 623 patients undergoing allo-HCT between 2000 - 2016 in the USA (CIBMTR cohort). A Cox multivariable model was used to identify factors prognostic of mortality. A weighted score using these factors...
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) that has shown efficacy in B-cell non-Hodgkin’s lymphoma. It has shown high efficacy in relapsed/refractory follicular lymphoma (FL) even in the presence of high risk features (early relapse, heavily pretreated patients and bulky disease)....
Before the advent of tyrosine kinase inhibitors (TKI) the outcome of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was dismal. The TKI combination with induction regimens has greatly improved the long-term outcome of Ph+ ALL, specifically ponatinib a most potent TKI in combination with HyperCVAD (hyperfractionated cyclop...
There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres...
Literature discussing endemic and regionally limited infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America is scarce. This Worldwide Network for Blood and Marrow Transplantation (WBMT) article is part one of two papers aiming to provide guidance to transplantation centres around the glo...
COVID-19 adversely affects individuals with cancer. Several studies have found that seroconversion rates among patients with hematologic malignancies are suboptimal when compared to patients without cancer. Patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addit...
The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients...
Background:
Allogeneic stem cell transplantation (alloSCT) is the only known curative treatment for myelofibrosis (MF). Risk assessment remains important for patient counseling and predicting survival outcomes for relapse and non-relapse mortality (NRM). Outcome-prediction tools can guide decision-making. Their use in MF has relied on their extrap...
Post-transplantation cyclophosphamide (PTCy) and calcineurin inhibitor (CNI) based graft versus host disease (GVHD) prophylaxis has shown lower rates of acute and chronic GVHD when compared with the traditional prophylaxis of CNI and methotrexate (MTX) in matched related (MRD) and matched unrelated donor (MUD) allogeneic hematopoietic cell transpla...
Introduction:
Chimeric antigen receptor T (CAR T) cell therapy epitomizes the success of T cell engineering. Today, it is an integral component of the treatment algorithm for various types of B-cell non-Hodgkin lymphoma (NHL). Large B-cell lymphoma (LBCL) is the most common subtype of NHL accounting for 30-35% of cases. A lack of response to secon...
Patients with relapsed and/or refractory (R/R) follicular lymphoma (FL) and mantle cell lymphoma (MCL) have a poor prognosis with anticipated short progression-free and overall survivals. Two CD19-directed chimeric antigen receptor T-cell (CAR T) therapies are approved in the United States for R/R FL, namely, axicabtagene ciloleucel (axi-cel) and t...
Chimeric antigen receptors (CARs) are synthetic engineered receptors with an antigen recognition domain derived from a high-specificity monoclonal antibody that can target surface molecules on tumor cells. T cells are genetically engineered to express CARs, thereby harnessing the antigen-recognition ability of antibodies and effector function of T...
Purpose:
The optimal approach to incorporate radiotherapy (RT) in conjunction with CAR T-cell Therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (bNHL) remains unclear. This study documents the RT local control rate among patients who received bridging radiotherapy (BRT) prior to CART and compares it to those who received sal...
Chimeric antigen receptor T-cell (CAR T-cell) therapy represents an innovative and transformative therapy for patients with relapsed and/or refractory (R/R) hematological malignancies. CAR T-cell therapy was first approved in R/R diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia, today the use of CAR T-cell therapy has expanded...
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN also can invade other extramedullary compartments including the central nervous system. Generall...
Chimeric antigen receptor T-cell (CAR T) therapy has been proven effective in the third-line (and beyond) setting in patients with large B-cell lymphoma (LBCL). Until recently, high-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) was considered the standard of care in the second-line setting in patients demons...
Chimeric antigen receptor T cell (CAR-T) therapy is an immunotherapy, which represents a therapeutic breakthrough in the treatment of B-cell malignancies and multiple myeloma. Since the first CAR T-cell approval in 2017, there have been five FDA approved CAR-T products, more approved disease indications for CAR-T therapy, and investigational trials...
Purpose/Objective(s)
Significant relapse rates following CD19 Chimeric Antigen Receptor T-Cell Therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) remain a challenge. This study aims to better define the role of salvage radiotherapy (SRT) after CART.
Materials/Methods
We retrospectively reviewed 48 patients with r/r aggr...
Purpose/Objective(s)
The optimal way to utilize radiotherapy (RT) in conjunction with CD19 chimeric antigen receptor T-cell therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) remains unclear. RT can be used as bridging treatment (BRT) prior to CART cell infusion, or as salvage intervention (SRT) following CART for patien...
We investigated the impact of the number of induction/consolidation cycles on outcomes of 3113 adult AML patients who received allogeneic hematopoietic cell transplantation (allo-HCT) between 2008 and 2019. Patients received allo-HCT using myeloablative (MAC) or reduced-intensity (RIC) conditioning in first complete remission (CR) or with primary i...
Outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult acute lymphoblastic leukemia (ALL) have improved over time. Studies have shown that total body irradiation (TBI) is the preferable type of myeloablative conditioning (MAC). However, outcomes based on central nervous system (CNS) involvement, namely CNS-positive versus CN...
The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo‐HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adult...
Background
: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only known treatment modality that can offer the possibility of cure for acute myeloid leukemia (AML). Unfortunately, relapse and/or disease progression still occurs in over one-third of cases even when patients are allografted in complete hematologic remission (CR)....
Allogeneic hematopoietic cell transplantation (alloHCT) can potentially salvage large B-cell lymphoma (LBCL) patients experiencing treatment failure after chimeric antigen receptor T-cell therapy (CAR-T). Nonetheless, data on the efficacy and toxicities of alloHCT after receipt of CAR-T are limited. We report a multicenter retrospective study asses...
Intravascular lymphoma (IVL) is a rare extranodal non‐Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003–2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS inv...
Citations
... For HC, CR was achieved when gross hematuria disappeared. If it persisted but improved in at least one grade, it was was considered PR (38). Overall response, overall survival and event-free survival were calculated from first MSC infusion. ...
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... Moreover, much more often seen than TCL, there are many reports of myeloid neoplasms following CART (17,27,28,33,83,84), including a recent boxed warning from the FDA of cilta-cel because 10% of the patients from their pivotal trial CARTITUDE-1 developed myeloid neoplasms (13). It is unclear if the development of subsequent myeloid malignancies is related to receipt of CART itself or to the fact that this is a heavily pretreated population already at risk of therapy-related myeloid neoplasm and perhaps now is experiencing longer survival from their underlying disease due to CART (77)(78)(79). ...
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... [5][6][7][22][23][24][25][26][27][28][29] Lastly, our study further confirms the significant survival impact of CAR-T therapy on frail, older patients with RR LBCL, who historically had a dismal prognosis. 4,[30][31][32] In our study, the rates of grade ≥3 CRS and ICANS were similar among various age groups. This supports the feasibility and safety of CAR-T therapy regardless of the chronological age. ...
... 36,39 Preliminary results from a retrospective study on CAR T-cells in secondary CNS lymphomas also found that the prognosis was better when there was no active CNS disease at the time of CAR T-cell infusion. 40 The tumor volume may have an influence on the response to CAR T-cells, as previously shown in systemic lymphomas. 41,42 Further studies will be necessary to assess the benefit of trying different bridging therapies, when the previous therapies failed, to obtain any response before CAR T-cells injection. ...
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... When focusing on patients with early treatment failure, the same was true for the 2-year relapse rate and PFS, while there was no difference in OS. In the multivariate regression analysis, treatment with CAR T-cells compared to ASCT showed a higher risk of relapse (hazard ratio: 2.18; p <0.0001) and an inferior PFS (hazard ratio: 1.83; p = 0.0011), while there was no difference for OS (hazard ratio: 1.44; p = 0.12) [41] Table 3. ...
... Utilizing radiation as a bridging therapy for axi-cel in patients with aggressive lymphomas demonstrated comparable adverse effect profile, favorable in-field disease control and no major impact on the feasibility of CAR-T manufacturing [38,39]. However, there is limited data on the role of radiation therapy prior to ide-cel in RRMM. ...
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... A possible mechanism of resistance could be the selection of CLL clones with reduced expression of CD19 under the pressure of anti-CD19 CAR-T cell therapy [73]. Consequently, a potentially effective strategy to overcome resistance to anti-CD19 CAR-T cells might involve the development of cellular therapies which target B cell surface molecules that are different to CD19 [74]. On these grounds, an innovative CAR-T construct (MC10029) has been designed to target the B cell-activating factor receptor (BAFF-R), a surface receptor that promotes B cell proliferation and maturation through the activation of the NF-κB pathway [74,75]. ...
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... It can also detect different maturation stages of pDCs based on characteristic patterns of antigen expression, which are typically not clearly appreciated by morphology and immunohistochemical stains. Flow cytometry analysis is particularly helpful in the assessment of minimal residual disease, which has proven to be of high clinical significance for disease risk stratification prior to and following stem cell transplantation [5]. Furthermore, different types of neoplastic pDC proliferations can be distinguished from each other using flow cytometry analysis. ...
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... As previously mentioned, generic formulations of plerixafor are becoming available, so cost will hopefully decrease in the near future, but our experience with other generics shows that this is not always the case. Motixafortide is even more expensive, at around $12,000 per vial [44] . Although plerixafor and motixafortide add additional upfront costs to mobilization, some of these expenses are offset by reductions in days of additional collection and associated costs including nursing, apheresis, and additional lab work. ...
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... The FDA-approved CAR-T products axicabtagene ciloleucel (axi-cel) [4], tisagenlecleucel (tisa-cel) [5], and lisocabtagene maraleucel (liso-cel) [6] in patients with relapsed and/or refractory LBCL after failure of two or more prior lines of chemotherapy starting in 2017. With improved access to these new therapies, as well as recent approval in the primary refractory or second line setting [7], increasing numbers of LBCL patients have undergone CAR-T treatment [8]. In patients prescribed CAR-T therapy [9], insurance authorization is obtained and a leukapheresis collection is completed for product manufacturing. ...
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