Similar outcomes of alemtuzumab-based hematopoietic cell transplantation for SAA patients older or younger than 50 years

Sheth, Vipul; Potter, Victoria; Gandhi, Shreyans; Kulasekararaj, Austin; Lavallade, Hugues de; Muus, Petra; Pagliuca, Antonio; Rice, Carmel; Mehra, Varun; Grimaldi, Francesco; Inam, Shafqat; Barber, Linda D.; Mufti, Ghulam J.; Marsh, Judith

doi:10.1182/bloodadvances.2019000480

Cited by 10 publications

(14 citation statements)

References 47 publications

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“…With improved survival after HSCT, the upper age limit for up-front MSD HSCT has steadily increased, according to comorbidities and fitness for HSCT. 68,[71][72][73][74][75] Up-front matched unrelated donor (MUD) HSCT may be considered as an option for young adults with SAA/VSAA who lack a MSD, who urgently need a transplant to achieve early neutrophil engraftment on account of severe/life-threatening sepsis, and where multiple MUDs are readily available and one is recruited to donate in a very short time frame. This reflects a similar approach in children, [76][77][78] although randomised controlled trials comparing IST with MUD are not yet available.…”

Section: Fir St-li N E Tr E Atm E N T Of Acqu Ir E D a Amentioning

confidence: 99%

See 1 more Smart Citation

Guidelines for the diagnosis and management of adult aplastic anaemia: A British Society for Haematology Guideline

Kulasekararaj,

Cavenagh,

Dokal

et al. 2024

Br J Haematol

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SummaryPancytopenia with hypocellular bone marrow is the hallmark of aplastic anaemia (AA) and the diagnosis is confirmed after careful evaluation, following exclusion of alternate diagnosis including hypoplastic myelodysplastic syndromes. Emerging use of molecular cyto‐genomics is helpful in delineating immune mediated AA from inherited bone marrow failures (IBMF). Camitta criteria is used to assess disease severity, which along with age and availability of human leucocyte antigen compatible donor are determinants for therapeutic decisions. Supportive care with blood and platelet transfusion support, along with anti‐microbial prophylaxis and prompt management of opportunistic infections remain key throughout the disease course. The standard first‐line treatment for newly diagnosed acquired severe/very severe AA patients is horse anti‐thymocyte globulin and ciclosporin‐based immunosuppressive therapy (IST) with eltrombopag or allogeneic haemopoietic stem cell transplant (HSCT) from a matched sibling donor. Unrelated donor HSCT in adults should be considered after lack of response to IST, and up front for young adults with severe infections and a readily available matched unrelated donor. Management of IBMF, AA in pregnancy and in elderly require special attention. In view of the rarity of AA and complexity of management, appropriate discussion in multidisciplinary meetings and involvement of expert centres is strongly recommended to improve patient outcomes.

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Section: Fir St-li N E Tr E Atm E N T Of Acqu Ir E D a Amentioning

confidence: 99%

“…Outcomes in older patients, including those over 70 years, have improved, 72,74,122 but the presence of comorbidities impacts on outcome. A conditioning protocol that minimises GVHD is advocated.…”

Section: Syngeneic Donormentioning

confidence: 99%

Guidelines for the diagnosis and management of adult aplastic anaemia: A British Society for Haematology Guideline

Kulasekararaj,

Cavenagh,

Dokal

et al. 2024

Br J Haematol

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“…An age cut‐off of 40 has been applied given the higher transplant mortality in patients over this age 97,105–107 . Some centres extend to age 50 in very selected cases when comorbidities and performance status are not limiting 108,109 . Nonetheless, most AA patients worldwide receive a non‐transplant treatment modality given age, comorbidities, lack of a suitable donor, lack of access to transplant, or patient’s choice.…”

Section: Therapymentioning

confidence: 99%

“…97,[105][106][107] Some centres extend to age 50 in very selected cases when comorbidities and performance status are not limiting. 108,109 Nonetheless, most AA patients worldwide receive a nontransplant treatment modality given age, comorbidities, lack of a suitable donor, lack of access to transplant, or patient's choice. Some have advocated for a MUD HSCT upfront in younger patients.…”

Section: Therapymentioning

confidence: 99%

Acquired severe aplastic anaemia: how medical therapy evolved in the 20th and 21st centuries

Scheinberg

2021

Br J Haematol

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The progress in aplastic anaemia (AA) management is one of success. Once an obscure entity resulting in death in most affected can now be successfully treated with either haematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). The mechanisms that underly the diminution of haematopoietic stem cells (HSCs) are now better elucidated, and include genetics and immunological alterations. Advances in supportive care with better antimicrobials, safer blood products and iron chelation have greatly impacted AA outcomes. Working somewhat 'mysteriously', anti-thymocyte globulin (ATG) forms the base for both HSCT and IST protocols. Efforts to augment immunosuppression potency have not, unfortunately, led to better outcomes. Stimulating HSCs, an often-sought approach, has not been effective historically. The thrombopoietin receptor agonists (Tpo-RA) have been effective in stimulating early HSCs in AA despite the high endogenous Tpo levels. Dosing, timing and best combinations with Tpo-RAs are being defined to improve HSCs expansion in AA with minimal added toxicity. The more comprehensive access and advances in HSCT and IST protocols are likely to benefit AA patients worldwide. The focus of this review will be on the medical treatment advances in AA.

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“… 54 The most frequently used unrelated HCT regimens for AA patients, either fludarabine, ATG, cyclophosphamide and 2 Gy TBI or fludarabine combined with Campath antibody, appeared to produce similar results, including for older patients. 121 , 122 Moreover, recent papers reported outstanding survival figures for AA patients given HLA-haploidentical grafts. 123 , 124 Taken together, these findings suggested that upfront marrow transplantation should be considered for all patients with AA who have a suitable donor rather than waiting until failure of immunosuppressive therapy.…”

Section: Current Trendsmentioning

confidence: 99%

History of hematopoietic cell transplantation: challenges and progress

Granot

Storb

2020

haematol

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After more than 60 years of research in allogeneic hematopoietic cell transplantation (HCT), this therapy has advanced from one that was declared dead in the 1960s to a standard treatment of otherwise fatal malignant and non-malignant blood diseases. To date, close to 1.5 million hematopoietic cell transplants have been performed in more than 1,500 transplantation centers worldwide. This review will highlight the enormous efforts by numerous investigators throughout the world who have brought the experimental field of HCT to clinical reality, examine ongoing challenges, and provide insights for the future.

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Similar outcomes of alemtuzumab-based hematopoietic cell transplantation for SAA patients older or younger than 50 years

Abstract: Key Points GRFS is similar between older and younger patients using FCC conditioning but comorbidities impact on outcome of SAA HSCT. Immunomodulatory B lymphocytes potentially contribute to control of alloreactivity and low GVHD after FCC HSCT.

Cited by 10 publications

References 47 publications

Guidelines for the diagnosis and management of adult aplastic anaemia: A British Society for Haematology Guideline

Guidelines for the diagnosis and management of adult aplastic anaemia: A British Society for Haematology Guideline

Acquired severe aplastic anaemia: how medical therapy evolved in the 20th and 21st centuries

History of hematopoietic cell transplantation: challenges and progress

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