Hematopoietic Cell Transplantation for Adult Acute Myeloid Leukemia

Appelbaum, Frederick R.

doi:10.1002/9781118416426.ch50

Cited by 3 publications

(1 citation statement)

References 91 publications

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“…Similarly, our study demonstrated no effect of significant ABO incompatibility on neutrophil or platelet recovery independent of donor type, conditioning regimen, or stem cell source except for increased platelet and red cell transfusions. These findings are consistent with prior research, which found that substantial ABO mismatch had little effect on engraftment [ 30 ].…”

Section: Discussionsupporting

confidence: 93%

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan

Borhany,

Ali,

Ghias

et al. 2023

Cureus

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Background and objective Allogeneic hematopoietic stem cell transplantation (alloHSCT) provides curative treatment for several hematological illnesses. In this study, we evaluated the impact of ABO compatibility and incompatibility on outcomes and complications related to hematopoietic stem cell transplantation (HSCT) performed for various hematological disorders at our center. Methodology This was a retrospective, single-center, cohort study in which patients were categorized according to the ABO match and mismatch status. The mismatch group was further subcategorized into major, minor, and bidirectional groups. Results A total of 117 patients underwent alloHSCT, out of which 82 (70.1%) were male and 35 (30%) were female. The median age of the patients was 9.5 years (range: 46 years). The most common indications for stem cell transplant were beta-thalassemia major (BTM; n=58, 49%) and aplastic anemia (AA; n=42, 35.8%). However, the outcomes in match and mismatch groups showed significant results for positive direct Coombs test (DCT), indicating the occurrence of hemolysis. Despite the increased need for blood transfusions, ABO blood group incompatibility (ABOi) had no negative impact on the clinical results. Conclusion Based on our findings, ABO incompatibility does not affect the outcomes in patients undergoing alloHSCT. Patient monitoring can aid in early detection and treatment, thereby minimizing the frequency of fatal events.

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Section: Discussionsupporting

confidence: 93%

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan

Borhany,

Ali,

Ghias

et al. 2023

Cureus

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CKS1-dependent proteostatic regulation has dual roles combating acute myeloid leukemia whilst protecting normal hematopoiesis

Grey

Río-Machín²,

Casado-Izquierdo³

et al. 2020

Preprint

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Acute myeloid leukemia (AML) is an aggressive hematological disorder comprising a hierarchy of quiescent leukemic stem cells (LSCs) and proliferating blasts with limited self-renewal ability. AML has a dismal prognosis, with extremely low two-year survival rates in the poorest cytogenetic risk patients, primarily due to the failure of intensive chemotherapy protocols unable to deplete LSCs, which reconstitute the disease in vivo, and the significant toxicity towards healthy hematopoietic cells. Whilst much work has been done to identify genetic and epigenetic vulnerabilities in AML LSCs, little is known about protein dynamics and the role of protein degradation in drug resistance and relapse. Here, using a highly specific inhibitor of the SCFSKP2-CKS1 complex, we report a dual role for CKS1-dependent protein degradation in reducing AML blasts in vivo, and importantly depleting LSCs. Whilst many AML LSC targeted therapies show significant toxicity to healthy hematopoiesis, inhibition of CKS1-dependent protein degradation has the opposite effect, protecting normal hematopoietic cells from chemotherapeutic toxicity. Together these findings demonstrate CKS1-dependent proteostasis is key for normal and malignant hematopoiesis.SignificanceCKS1-dependent protein degradation is a specific vulnerability in AML LSCs. Specific inhibition of SCFSKP2-CKS1 is lethal to CKS1Bhigh AML blasts and all AML LSCs. Normal hematopoiesis is protected from chemotherapeutic toxicity by inhibition of CKS1-dependent protein degradation, substantiating a dual role for CKS1-dependent protein degradation in clinical treatment of AML.

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Tumorablative Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of High-Risk and Refractory Leukemia — New Concepts and Clinical Practice

Da¹

2013

Innovations in Stem Cell Transplantation

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The substance of bone marrow transplantation is the organ transplantation. "ccurately, it is the grafting of hematopoietic and immunologic system. Comparing to the transplantation of solid organ, in the hematopoietic stem cell transplantation HSCT , the ill organ, id est. hematopoietic and immunology system, is ablated by high-dose chemotherapy and total body irradiation T"I conditioning regime . Thus, the normal hematopoietic stem cells could be engrafted and normal function of hematopoietic and immune system could be reconstituted. The standard myeloablative conditioning regimen would be reasonable or enough for the non-malignances of marrow, which needed by replacing therapy, such as marrow failure. However, for treatment of hematopoietic malignances, it maybe not cure the malignance diseases to ablate the normal hematopoietic, immune system and reconstitute the normal function of allogeneic hematopoietic and immune system of patients. "ecause the leukemic stem cells LSC are not only existence in the bone marrow, it might be occurrence in any site of body. For instance, the traditional myeloablative conditioning regimen to treat leukemia could have striking killing effects of leukemic cells, and residual leukemic cells further eradicated by effect of the graft versus leukemia GVL , but the malignant cells are not always removed at all in the all patients, therefore, relapse post transplantation could be occurred in the some patients. In fact, the traditional allogeneic myeloablative HSCT could cure or improve outcome of acute leukemic patients with standard risk, however, the disease relapse after transplant for acute leukemia with high risk and refractory is % to % [ -]. Moreover, the leukemic cells in the majority of relapsed cases originate from inceptive

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Hematopoietic Cell Transplantation for Adult Acute Myeloid Leukemia

Cited by 3 publications

References 91 publications

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan

CKS1-dependent proteostatic regulation has dual roles combating acute myeloid leukemia whilst protecting normal hematopoiesis

Tumorablative Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of High-Risk and Refractory Leukemia — New Concepts and Clinical Practice

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