15 results on '"Arslan, Shukaib"'
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2. Risks and Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in Patients with HIV Infection.
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Arslan, Shukaib, Litzow, Mark R., Cummins, Nathan W., Rizza, Stacey A., Badley, Andrew D., Navarro, Willis, and Hashmi, Shahrukh K.
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HEMATOPOIETIC stem cell transplantation , *HIV-positive persons , *HEMATOLOGIC malignancies , *ALEMTUZUMAB , *CELL transplantation , *GRAFT versus host disease - Abstract
• The long-term outcomes of patients living with HIV who undergo allogeneic transplant are somewhat similar to those without HIV. • Prospective trials are urgently needed to evaluate the optimal donor, stem cell source, conditioning regimen, and graft-versus-host disease prophylaxis. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies in persons living with HIV (PLHIV), however, uncertainties exist in many domains related to their care, including optimal donor selection, conditioning regimen, immunosuppression for graft-versus-host disease (GVHD), and long-term outcomes. We undertook a comprehensive systematic review from multiple databases to evaluate the foregoing uncertainties. The final sample comprised 49 patients (median age at HCT, 34 years; 46 males [93.8%]). Acute GVHD (aGVHD) was reported in 19 patients (59.3%) in the overall cohort, with grade II in 12 (37.5%) and grade III in 2 (6.2%). In the entire cohort, overall survival (OS) was 81.6% at 6 months and 56.6% at 12 months. Among 32 patients, the OS at 6 months was 73.3% for patients who received myeloablative conditioning (MAC) and 88.2% for those who received reduced-intensity conditioning (RIC), and OS at 12 months was 53.3% for MAC and 58.8% for RIC. Twenty-four patients were alive in complete remission on long-term follow-up, with 25 deaths reported. Fifteen deaths (60%) occurred due to relapse, including 3 (12%) from infection, 2 (8%) from GVHD, and 5 (20%) from other causes, including renal failure, respiratory failure, and liver failure. To our knowledge, this is the largest series of allo-HCT in PLHIV reported to date, and our results indicate that clinical outcomes (including engraftment, infection rate, and survival) are not significantly different from those in patients without HIV (historical controls). RIC regimens are associated with a slightly greater likelihood of survival compared with MAC regimens. Prospective trials are critically needed to evaluate the optimal conditioning regimens, ideal donor source, and most appropriate GVHD prophylaxis. [ABSTRACT FROM AUTHOR]
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- 2019
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3. Ibrutinib for Pure Red Cell Aplasia after Allogeneic Hematopoietic Stem Cell Transplant with Major ABO Incompatibility.
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Arslan, Shukaib, Stein, Anthony S., Forman, Stephen J., Nakamura, Ryotaro, and Al Malki, Monzr M.
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BLOOD group incompatibility , *PURE red cell aplasia , *HEMATOPOIETIC stem cells , *STEM cell transplantation , *ABO blood group system , *RITUXIMAB , *HLA histocompatibility antigens - Abstract
Since Human leukocyte antigen (HLA) and ABO blood group system are inherited independently and with up to 50% of allogeneic hematopoietic cell transplantations (HCT) are performed with donor-recipient ABO incompatibility, recipients are at increased risk for acute and delayed hemolytic reaction and delayed RBC precursors engraftment; i.e. pure RBC aplasia (PRCA). PRCA is a sever consequence of major and bi-directional ABO mismatch after alloHCT, leading to frequent transfusions, iron overload and secondary complications. Risk factors for PRCA after Major ABO incompatibility include; stem cell source, conditioning intensity, and titer of iso-agglutinins. Treatment is mostly supportive with transfusions and growth factors as well as withdrawing immunosuppressive therapy (IS). Targeting recipient immune system with high-dose steroids, DLI, and rituximab have been reported with variable results. Here we report a case series of a novel method of targeting recipient iso-agglutinins-producing B cells by Ibrutinib. We report 3 cases of PRCA refractory to conventional therapy who responded to ibrutinib, a BTK inhibitor targeting recipient B cells to allow engraftment of donor RBCs. Patient, transplant and disease characteristic including prior therapies, time to transfusion independence, and switch of blood group (BG) are summarized in Table 1. First patient's day 30 post-transplant bone marrow biopsy (BMBx) showed complete remission (CR) with full donor chimera, but BG remained O. He developed severe anemia requiring transfusions and Day 100 BMBx showed CR with markedly decreased number of erythroid progenitors. He did not respond to IS withdrawal, prednisone, rituximab or bortezomib. But BMBx 4 weeks after starting ibrutinib showed trilineage hematopoiesis. Second patient remained RBC transfusion dependent post-HCT with Day 100 biopsy showing PRCA and full donor chimera. BG remained O. He developed severe GVHD of skin and eyes after DLI and His PRCA was refractory to multiple lines of therapies but responded to ibrutinib. Third patient underwent HCT for refractory AML with MDS; Anti-A isoagglutinin level pre-HCT was high and patient underwent plasma exchange. Day 30 BMBx showed CR and full donor chimera. Day +73 BMBx showed CR with near absent erythropoiesis. PRCA was refractory to rituximab and responded to ibrutinib. All three patients with PRCA refractory to multiple lines of therapy responded to ibrutinib with median time to transfusion independence of 4 weeks and median time to BG switch of 6 weeks. All patients tolerated therapy well. Our experience at City of Hope shows that ibrutinib could offer a safe and efficacious treatment option for cases of refractory PRCA. Prospective studies are needed to assess if early therapy with ibrutinib could reduce the morbidity resulting from frequent transfusions, and GVHD complications. [ABSTRACT FROM AUTHOR]
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- 2020
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4. High remission rates and transition to allogeneic transplant in older patients with newly diagnosed FLT-3 mutated acute myelogenous leukemia with midostaurin plus intensive chemotherapy.
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Tinajero, Jose, Ngo, Dat, Zhang, Jianying, Tsai, Ni-Chun, Aribi, Ahmed, Aldoss, Ibrahim, Agrawal, Vaibhav, Arslan, Shukaib, Amanam, Idoroenyi, Pourhassan, Hoda, Sandhu, Karamjeet, Al-Malki, Monzr, Pullarkat, Vinod, Becker, Pamela, Nakamura, Ryotaro, Stein, Anthony, Marcucci, Guido, Artz, Andrew, Koller, Paul, and Salhotra, Amandeep
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ACUTE myeloid leukemia , *OLDER patients - Abstract
This document presents data on the outcomes and toxicities of a treatment regimen for older adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML). The study found that the treatment approach, which included induction chemotherapy with the addition of midostaurin, resulted in a high complete remission rate and a median overall survival of 9.3 months. Additionally, a significant number of patients underwent allogeneic hematopoietic stem cell transplantation (allo-HCT) with favorable outcomes. The authors conclude that this treatment approach is feasible and effective for older adults with FLT3-mutated AML. However, the study lacked long-term follow-up and data on minimal residual disease achievement and allo-HCT outcomes. [Extracted from the article]
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- 2024
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5. 493 - Outcomes and Risks of Allogeneic Hematopoietic Stem Cell Transplant for Hematological Malignancies in Patients with HIV Infection.
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Arslan, Shukaib, Cummins, Nathan W., Rizza, Stacey A., Badley, Andrew D., Litzow, Mark R., Navarro, Willis H., and Hashmi, Shahrukh K.
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- 2018
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6. 164 - Outcomes and Risks of Autologous Hematopoietic Stem Cell Transplant for Hematological Malignancies in Patients with HIV Infection.
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Arslan, Shukaib, Lee, Jessica, Shoukat, Sonia, Cummins, Nathan W., Badley, Andrew D., Litzow, Mark R., Navarro, Willis H., and Hashmi, Shahrukh K.
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- 2018
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7. WT1-mutated acute myeloid leukemia is sensitive to fludarabine-based chemotherapy and conditioning regimens.
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Aribi, Ahmed, Salhotra, Amandeep, Afkhami, Michelle, Munteanu, Anamaria, Ali, Haris, Aldoss, Ibrahim, Otoukesh, Salman, Al Malki, Monzr M., Sandhu, Karamjeet S., Koller, Paul, Arslan, Shukaib, Stewart, Forrest, Artz, Andrew, Curtin, Peter, Ball, Brian, O'Hearn, James, Spielberger, Ricardo, Smith, Eileen, Budde, Elizabeth, and Nakamura, Ryotaro
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ACUTE myeloid leukemia , *STEM cell transplantation , *CANCER chemotherapy , *FLUDARABINE - Abstract
We conducted a retrospective analysis of WT1-mutated acute myeloid leukemia (AML) patients who underwent allogeneic stem cell transplant. Thirty-seven patients with WT1-mutated AML were identified. Primary induction failure (40%) and early relapse rate (18%) after idarubicin/cytarabine (7 + 3) chemotherapy were observed. All patients with induction failure subsequently achieved CR with additional chemotherapy. There was no significant difference between outcomes after myeloablative vs. reduced intensity (Fludarabine/Melphalan [Flu/Mel]) conditioning regimens. RFS but not OS was significantly better in patients who received FLAG-IDA prior to transplant and/or a fludarabine-containing conditioning. In an independent ex vivo study, WT1-mutated AML samples exhibited greater sensitivity to fludarabine (p = 0.026) and melphalan (p = 0.0005) than non-WT1-mutated AML samples while there was no difference between sensitivity to cytarabine. Our data favor using a fludarabine-based induction for AML with WT1 mutation instead of 7 + 3. Fludarabine conditioning regimens for alloHCT showed better RFS but not OS. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Use of monoclonal antibody therapy in hematologic patients with mild-to-moderate COVID-19: A retrospective single-center experience.
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Amanam, Idoroenyi, Janny Yao, Puing, Alfredo, Ni-Chun Tsai, Samuels, Diana, Dat Ngo, Stephanie Ho, Ali, Haris, Aribi, Ahmed, Arslan, Shukaib, Artz, Andrew, Myo Htut, Koller, Paul, Salhotra, Amandeep, Sandhu, Karamjeet, Liana Nikolaenko, Pawlowska, Anna, Shouse, Geoffrey, Stein, Anthony, and Marcucci, Guido
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COVID-19 , *MONOCLONAL antibodies , *VIRAL shedding , *HEMATOLOGIC malignancies - Abstract
Introduction: In November 2020, the FDA issued an emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild-to-moderate COVID-19 at high risk for disease progression. Methods: We retrospectively reviewed 38 adult hematology patients who received mAbs from 11/2020 to 2/2021. Results: Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab-imdevimab. Four (11%) patients were hospitalized due to COVID-19, two (5%) progressed to severe disease and one patient (3%) died within 30 days from COVID-19 disease. Most patients (n = 34, 89%) ultimately tested negative for SARS-CoV-2, with 34% (n = 13) clearing the virus within 14 days after mAb infusion. The median time to clearance of viral shedding was 25.5 days (range: 7-138). After mAb infusion, most patients with hematological malignancies (HM) (n = 10/15; 67%) resumed therapy for underlying disease with a median delay of 21.5 days (range: 12-42). We observed a significant difference in hospitalization among patients who received a HCT versus non-HCT (0% n = 0/26 and 36% n = 4/11, respectively; p < 0.01). Conclusions: This study demonstrates that SARS-CoV-2 specific mAb was safe and may reduce hospitalization compared to what is reported in malignant hematology patients at high risk for disease progression. Our HCT cohort patients had less hospitalization rate compared with HM cohort patients. [ABSTRACT FROM AUTHOR]
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- 2023
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9. The impact of SARS-CoV2 vaccines on the incidence of graft versus host disease in allogeneic hematopoietic stem cell transplant recipients: a single-center retrospective study.
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Ngo, Dat, Chen, Jason, Tinajero, Jose, Aribi, Ahmed, Arslan, Shukaib, Marcucci, Guido, Nakamura, Ryotaro, Al Malki, Monzr M., Forman, Stephen J., Dadwal, Sanjeet, and Ali, Haris
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GRAFT versus host disease , *HEMATOPOIETIC stem cells , *STEM cell transplantation , *SARS-CoV-2 , *HEMATOPOIETIC stem cell transplantation - Abstract
This study reports the incidence of chronic graft versus host disease (GvHD) in allogeneic hematopoietic stem cell transplant (alloHCT) recipients who received SARS-CoV2 vaccination. The overall rates of new and worsening chronic GvHD combined were 14%, with median time from vaccination to GVHD being approximately three to four weeks. A majority of the cases were of mild to moderate severity and primarily localized to either the skin, mouth, or joints. Prior chronic GVHD and recent transplant were associated with higher GVHD rates following COVID-19 vaccination. More prospective studies are needed to provide a definitive mechanism for the impact of SARS-CoV2 vaccination on alloHCT patients. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation.
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Desai, Amrita, Samara, Yazeed, Yang, Dongyun, Ball, Brian, Braun, Adam, Koller, Paul, Blackmon, Amanda, Agrawal, Vaibhav, Pourhassan, Hoda, Amanam, Idoroenyi, Arslan, Shukaib, Otoukesh, Salman, Sandhu, Karamjeet, Aldoss, Ibrahim, Ali, Haris, Salhotra, Amandeep, Al Malki, Monzr M., Artz, Andrew, Becker, Pamela, and Smith, Eileen
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NUCLEOTIDE sequencing , *GRAFT versus host disease , *HEMATOPOIETIC stem cell transplantation , *PROGRESSION-free survival , *TREATMENT effectiveness , *CHRONIC leukemia - Abstract
Allogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes. To compare outcomes of MDS/CMML patients with and without spliceosome mutations undergoing allo-HCT. This is a single institution, retrospective study of MDS/CMML patients who underwent allo-HCT with myeloablative or reduced intensity conditioning (RIC) regimen at City of Hope from January 2016 to December 2021. Among them, patients who underwent molecular mutation profiling by NGS (Next Generation Sequencing) for a set of genes known to be mutated in myeloid neoplasms are included in this analysis. We compared OS, relapse free survival, NRM and acute/chronic graft versus host disease (GVHD) incidence between the spliceosome-mutated and unmutated groups. We identified 258 consecutive MDS/CMML patients who underwent allo-HCT. Of these, 126 (48.8 %) patients had molecular profiling done among whom 57 (45.2 %) patients carried a spliceosome mutation. 84.9 % of patients had MDS and 55.6 % underwent a matched unrelated donor transplant. The median age for the whole cohort was 66 years (range 12–77).78.6 % and 73.7 % received RIC in the spliceosome and non-spliceosome groups, respectively. The 2-year OS for the whole cohort was 66.5 % (95 %CI 0.55–0.75) with a day 100 NRM of 7.1 % and 2-year cumulative incidence of relapse of 20 %. Grade II-IV acute GVHD at day 100 was 36.3 % (95 % CI 0.27–0.44) and any chronic GVHD at 2-years was 48.4 % (95 % CI 0.37–0.58). Patients who carried a spliceosome mutation had a significantly better 2-year survival of 83.8 % vs 55.9 % in the non-spliceosome group (P=0.002) and a better PFS of 73.7 % vs 50.0 % (P=0.007). There was no difference in the cumulative incidence of relapse at 2-years 15.9 % vs 18.5 % (P=0.59) between two groups but the spliceosome group had a significantly lower NRM at 2-years 10.4 % vs 31.5 % (P=0.009). There was no difference in incidence of acute or chronic GVHD between the two groups. Among patients with MDS or CMML who underwent allo-HCT, our study shows better OS for patients who have spliceosome mutations due to lower NRM compared to those carrying non- spliceosome mutations. This favorable outcome of the spliceosome-mutated patients could have implications for timing of allo-HCT, particularly for patients in the intermediate MDS prognostic risk groups. • Spliceosome-mutated MDS is associated with better overall and disease free survival after alloHCT compared to non-spliceosome mutated DS. • The better overall survival for spliceosome-mutated group was due to lower non relapse mortality after alloHCT. • AlloHCT could be considered early for spliceosome-mutated patients given excellent alloHCT outcome. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia.
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Aldoss, Ibrahim, Otoukesh, Salman, Zhang, Jianying, Mokhtari, Sally, Ngo, Dat, Mojtahedzadeh, Mona, Al Malki, Monzr M., Salhotra, Amandeep, Ali, Haris, Aribi, Ahmed, Sandhu, Karamjeet S., Arslan, Shukaib, Koller, Paul, Ball, Brian, Stewart, Forrest, Curtin, Peter, Artz, Andrew, Nakamura, Ryotaro, Marcucci, Guido, and Forman, Stephen J.
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EXTRAMEDULLARY diseases , *LYMPHOBLASTIC leukemia , *ACUTE leukemia , *DISEASE relapse , *DISEASE progression - Abstract
Background: Blinatumomab has demonstrated encouraging activity in relapsed/refractory (r/r) and minimal residual disease–positive (MRD+) acute lymphoblastic leukemia (ALL). Extramedullary disease (EMD) relapse or relapse with CD19– disease has been observed after blinatumomab therapy in patients with r/r or MRD+ ALL. However, the pathophysiology and risk factors of treatment failure are not fully understood. Methods: This study retrospectively reviewed the outcomes of adult patients with B‐cell ALL treated with blinatumomab (n = 132) for either r/r (n = 103) or MRD+ disease (n = 29) at the authors' center (2013‐2021) and analyzed factors associated with treatment response and EMD failure. Results: The overall response rate was 64%. A lower marrow blast burden before blinatumomab (P =.049) and no history of previous EMD (P =.019) were significantly associated with a higher response. Among the patients who responded to blinatumomab, 56% underwent consolidation with allogeneic transplantation. Blinatumomab failure was observed in 89 patients; 43% of these patients (n = 38) either progressed or relapsed at extramedullary sites. A history of extramedullary involvement (53% vs 24%; P =.005) and retention of CD19 expression at the time of relapse/progression (97% vs 74%; P =.012) were associated with a higher risk for extramedullary failure. Central nervous system (CNS) failure after blinatumomab was encountered in 39% of the patients with EMD. Conclusions: A history of EMD predicted an inferior response to blinatumomab therapy with a higher risk for relapse/progression at extramedullary sites (particularly CNS). Consolidation with allogenic transplantation in patients who primarily responded to blinatumomab did not abrogate the risk of extramedullary relapse. The incorporation of extramedullary assessment and the intensification of CNS prophylaxis may help in addressing extramedullary failure. Lay Summary: Extramedullary failure is common during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia.A history of extramedullary disease predicts an inferior response to blinatumomab therapy and a higher risk for relapse/progression at extramedullary sites.Most extramedullary failure cases retain CD19 expression. Extramedullary failure is common during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia. A history of extramedullary disease predicts an inferior response to blinatumomab therapy and a higher risk for relapse/progression at extramedullary sites. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Sequencing of novel agents in relapsed/refractory B‐cell acute lymphoblastic leukemia: Blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia.
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Badar, Talha, Szabo, Aniko, Dinner, Shira, Liedtke, Michaela, Burkart, Madelyn, Shallis, Rory M., Yurkiewicz, Ilana R., Kuo, Eric, Khan, Muhammad Ali, Balasubramanian, Suresh, Yang, Jay, Hefazi, Mehrdad, Podoltsev, Nikolai, Patel, Anand, Curran, Emily, Wang, Amy, Arslan, Shukaib, Aldoss, Ibrahim, Siebenaller, Caitlin, and Mattison, Ryan J.
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LYMPHOBLASTIC leukemia , *ACUTE leukemia , *HEMATOPOIETIC stem cell transplantation , *MEDICAL personnel , *TERMINATION of treatment - Abstract
Background: The availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B‐cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity. Methods: In this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared. Results: Among 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P =.73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety‐two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P =.09). Conclusions: Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL. Blinatumomab and inotuzumab ozogamicin have comparable efficacy as a first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia. The sequencing of these novel agents should be tailored according to individual patient needs. [ABSTRACT FROM AUTHOR]
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- 2021
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13. PEAMOtecan, a novel chronotherapeutic polymeric drug for brain cancer.
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Allen, Jasmine, Wang, Juan, Zolotarskaya, Olga Yu, Sule, Amrita, Mohammad, Sajjad, Arslan, Shukaib, Wynne, Kenneth J., Yang, Hu, and Valerie, Kristoffer
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BRAIN tumors , *POLYMERIC drugs , *GLIOBLASTOMA multiforme , *DNA topoisomerase I , *TREATMENT effectiveness , *DISULFIDES , *POLYETHYLENE glycol - Abstract
Glioblastoma multiforme (GBM) is an aggressive and difficult to treat form of brain cancer. In this work, we report on a novel chronotherapeutic polymeric drug, PEAMOtecan, for GBM therapy. PEAMOtecan was synthesized by conjugating camptothecin, a topoisomerase I inhibitor, to our proprietary, 'clickable' and modular polyoxetane polymer platform consisting of acetylene-functionalized 3-ethyl-3-(hydroxymethyl)oxetane (EAMO) repeat units (Patent No.: US 9,421,276) via the linker 3,3′-dithiodipropionic acid (DDPA) with a disulfide bond (S S) extended by short-chain polyethylene glycol (PEG). We show that PEAMOtecan is a highly modular polymer nanoformulation that protects covalently bound CPT until slowly being released over extended periods of time dependent on the cleavage of the disulfide and ester linkages. PEAMOtecan kills glioma cells by mitotic catastrophe with p53 mutant/knockdown cells being more sensitive than matched wild type cells potentially providing cancer-specific targeting. To establish proof-of-principle therapeutic effects, we tested PEAMOtecan as monotherapy for efficacy in a mouse orthotopic glioma model. PEAMOtecan was administered by one-time, convection-enhanced delivery (CED) intra-tumorally to achieve superior distribution and extended drug release over time. In addition, the near-infrared (NIR) dye Cy5.5 was coupled to the polymer providing live-animal imaging capability to track tissue distribution and clearance of the injected polymer over time. We show that PEAMOtecan significantly improves the survival of mice harboring intra-cranial tumors (p =.0074 compared to untreated group). Altogether, these results support further development and testing of our nanoconjugate platform. Unlabelled Image [ABSTRACT FROM AUTHOR]
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- 2020
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14. Clinical Outcome with Allogeneic Hematopoietic Stem Cell Transplantation after Blinatumomab or Inotuzumab Ozogamicin in Patients with B-Cell Acute Lymphoblastic Leukemia: Real World Experience.
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Badar, Talha, Advani, Anjali S., Liedtke, Michaela, Arslan, Shukaib, Khan, Muhammad Ali, Aldoss, Ibrahim, Sienbenaller, Caitlin, Schultz, Elizabeth, Hefazi, Mehrdad, Shallis, Rory Michael, Yurkiewicz, Ilana, Podoltsev, Nikolai, Patel, Anand, Curran, Emily, Kuo, Eric, Wang, Amy, Balasubramanian, Suresh, Yang, Jay, Mattison, Ryan, and Burkart, Madelyn
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HEMATOPOIETIC stem cell transplantation , *LYMPHOBLASTIC leukemia , *ACUTE leukemia , *GRAFT versus host disease , *KIDNEY transplant complications , *HEMATOPOIESIS , *HEMATOPOIETIC system , *RITUXIMAB - Abstract
Blinatumomab (Blina) and inotuzumab ozogamicin (Ino) have shown remarkable responses in relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL), however, a significant number of patients (pts) relapse. Prior reports suggest that allogeneic hematopoietic stem cell transplantation (SCT) consolidation after Blina/Ino may be associated with increased transplant related complications. To address this issue, we assembled a large retrospective multi-center cohort of RR ALL pts who received SCT after Blina/Ino. Medical records of RR ALL pts who received SCT after Blina or Ino at 11 academic transplant centers across USA were reviewed. These pts were evaluated for response and toxicity after SCT. From December 2014 to May 2019, 223 and 86 pts who received Blina and Ino, respectively, for RR ALL outside clinical trials were identified. Among them 85 (38%) pts in the Blina group (gp) and 21 (25%) pts in the Ino gp who achieved remission and underwent SCT were included in this analysis. Median age of pts in the Blina and Ino gp was 59 (range [R], 18-72) and 43 (R, 20-75) years, respectively. Median number (no.) of therapies (Rx) prior to SCT in Blina and Ino gp was 2, ranging from 2-5 and 2-6, respectively. Five (6%) and 2 (5%) pts in the Blina and Ino gp, respectively, received second SCT. Median time from remission to SCT in Blina gp was 1.7 months (mo) (R, 0.20 to 13.2) and in Ino gp was 4.3 mo (R, 1-13.3). In the Blina and Ino gp: 36.5% vs. 38%, 42% vs. 42%, 15% vs. 9.5% and 6% vs. 9.5% had matched related donor (MRD), matched unrelated donor (MUD), haploidentical and cord blood SCT, respectively. Acute graft versus host disease (aGVHD), chronic (c) GVHD, veno-occlusive disease (VOD) and infectious complications post SCT were observed in 28 (33%), 14 (16.5%), 2 (2%) and 12 (14%) pts, respectively, in the Blina gp. While in the Ino gp, 8 (38%), 1 (5%), 3 (14%) and 4 (19%) pts had these complications, respectively. Six (7%) and 2 (9%) pts had TRM within 100 days of SCT in Blina and Ino gp, respectively. The median PFS and OS in Blina gp was not reached (NR); 66% were progression free and 62% were alive at 2 yrs (Fig 1 A & B). Similarly, median PFS and OS in the Ino gp was NR; 53% were progression free at 6 mo and 53% were alive at 1 yr mark (Fig 1 C & D). In the Blina gp, history of CRS (p= 0.41), no. of prior Rx (p= 0.5), time from response to SCT (p=0.48), and type of donor (p= 0.7) were not significantly associated with GVHD. Similarly, in the Ino gp, no. of prior Rx (p= 0.6), time from response to SCT (p=0.84), type of donor (p= 0.9) were not significantly associated with GVHD. Occurrence of VOD in the Ino gp was not significantly associated with type of donor (p= 0.3), second SCT (p= 0.1), no. of prior Rx (p= 0.6), myeloablative conditioning (p> 0.9) or time from response to SCT (p= 0.5). Our real-world analysis suggests that SCT is feasible and effective after Blina or Ino in pts with RR ALL. [ABSTRACT FROM AUTHOR]
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- 2020
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15. A Phase II Trial of Post-Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis in HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation.
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Al Malki, Monzr M., Tsai, Ni-Chun, Palmer, Joycelynne, Mokhtari, Sally, Cao, Thai, Ali, Haris, Salhotra, Amandeep, Arslan, Shukaib, Aldoss, Ibrahim, Karras, Nicole, Zain, Jasmine, Khaled, Samer K., Stein, Anthony S., Snyder, David S., Marcucci, Guido, Forman, Stephen J., Nademanee, Auayporn, and Nakamura, Ryotaro
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GRAFT versus host disease , *CELL transplantation , *HEMATOPOIETIC system , *GRAFTING (Horticulture) , *ALEMTUZUMAB , *HEMATOLOGIC malignancies , *MYCOPHENOLIC acid , *PREVENTIVE medicine - Abstract
Despite of the continuous increase in the number of volunteer donors available through the registry, many patients who require an allogeneic hematopoietic cell transplantation (HCT) cannot find a fully-matched donor. While a mismatched unrelated donor (MMUD) is frequently available, it is associated with inferior outcomes and increased risk of graft-versus-host disease (GvHD). Post-transplant cyclophosphamide (PTCy) has been effective in haploidentical HCT, and increasingly used in matched donor HCTs. However, limited data exist in MMUD setting. We conducted a prospective single center trial (NCT 03128359) of PTCy for MMUD HCT with the primary objective of estimating 1-year GvHD-free relapse/progression-free survival (GRFS). As of October 2019, all planned 39 patients have been enrolled with a median follow up of 11 months (range: 1-23). Here we present the preliminary estimate of 1-year GRFS and other HCT outcomes in two strata; myeloablative conditioning (n=19) using Fludarabine (90 mg/m2) and FTBI (1200 cGy) or reduced intensity conditioning (n=19) using Fludarabine (100 mg/m2) and Melphalan (140 mg/m2 or 100 mg/m2 if >60 years old). Patients between 0 to 75 years of age and KPS of ≥70% with hematologic malignancies undergoing HCT from a 7/8 HLA-matched (A-, B-, C-, and DR-) donor were eligible. Patients with donor specific antibodies to the mismatched HLA-locus were excluded. All patient received PBMCs (3-5 × 106/kg) followed by GVHD prophylaxis consisting of PTCy (50 mg/kg for 2 days), Tacrolimus (1 mg), and mycophenolate mofetil (1 gr 3 × a day). Median age at the time of HCT was 53 years (range: 21-72), and 50% of patients were male. Disease risk was low in 47% (n=18), intermediate in 37% (n=14), and high in 16% of the patients (n=6). At transplant, 29 patients were in complete remission, and 9 had active disease. HCT-CI was 0 in six (16%) and 1-2 in 15 (39%) and >2 in 17 (45%) patients. Donors' median age was 32 years (range: 19-53) and donors were mismatched at HLA-A (n=14), -B (n=12), -C (n=8), or DR-loci (n=5). Median number of mismatches was 2 of 12 (range: 1-4). Female to male donor HCT was in 11% of recipients. Neutrophil engraftment occurred in all patients (median time to engraft: 16 days; range 13-35). One-year overall survival (OS) and GRFS were 92% (95% CI: 70-98) and 70% (95% CI: 51-83), respectively. Non-relapse mortality and relapse rate at 1 year were at 8% (95% CI: 2-29) and 13% (95% CI: 5-34), respectively. Cumulative incidence of day 100 acute GvHD grade 2-4 was 50% (95% CI: 35-71) and 1-year chronic GvHD was 56% (95% CI: 39-81). No severe chronic GvHD by the NIH criteria was observed. In conclusion, the data from our phase II trial of PTCy showed highly promising OS/GRFS in patients receiving 7/8 MMUD HCT, and that PTCy in MMUD setting offers an alternative and effective HCT approach for patients who do not have an available matched donor. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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