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Allogeneic stem cell transplantation

Replacing a patient's blood system with a donor's, so the donor's immune cells hunt down any leukaemia left behind. Still the only cure for many high-risk leukaemias.

Conditioning chemotherapy (myeloablative or reduced-intensity) followed by donor stem cells. The graft-versus-leukaemia effect provides ongoing immune surveillance; graft-versus-host disease is the price. Indicated in ELN adverse-risk AML in first remission, intermediate-risk with MRD positivity, relapsed disease, high-risk ALL, and Richter transformation. Post-transplant cyclophosphamide has made haploidentical donors routine; post-transplant maintenance (FLT3 inhibitors, azacitidine, menin inhibitors in trials) is reducing relapse.

Generic schematic · not to scale · placeholder for the cell therapy front
T cell + CAR transgene · CAR binds antigen (no MHC needed) · Tumour cell

How it works

Myeloablation eradicates host haematopoiesis; donor T cells recognise residual leukaemia via minor histocompatibility antigens.

Strengths
  • Curative for otherwise incurable leukaemia
  • Graft-versus-leukaemia is an antigen-agnostic immune therapy
Limitations
  • Treatment-related mortality 10-20%
  • Chronic GVHD
  • Relapse remains the main cause of failure
Since
1957

Products

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Key papers

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rctThe Lancet 2023changed practice
QuANTUM-First: quizartinib added to intensive chemotherapy and continued as maintenance in newly diagnosed FLT3-ITD AML

QuANTUM-First gave FLT3-ITD AML patients a second front-line targeted option and showed that continuing a FLT3 inhibitor as long-term maintenance, including after transplant, pays off. Quizartinib was approved for this indication in 2023. Head-to-head data against midostaurin are lacking, and the design leaves open how much of the benefit came from maintenance.

rctNew England Journal of Medicine 2019changed practice
ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia

ADMIRAL showed that a targeted oral drug can beat chemotherapy outright in relapsed AML, and made gilteritinib the standard bridge to transplant for FLT3-mutated relapse. Its success also underpinned FLT3 inhibitor use in first-line combinations. Resistance through FLT3-independent clones and RAS pathway mutations limits durability without transplant.

rctNew England Journal of Medicine 2016changed practice
INO-VATE: inotuzumab ozogamicin, a CD22 antibody-drug conjugate, versus chemotherapy for relapsed adult B-cell ALL

INO-VATE made inotuzumab a standard salvage therapy for adult ALL and a common route to transplant, and, with the TOWER trial of blinatumomab, moved adult ALL from chemotherapy-only salvage to immunotherapy. Both drugs have since been pulled into front-line regimens. The liver toxicity signal shaped how transplant conditioning is chosen after inotuzumab.

Latest papers

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Literature trend275 papers in the last 12 months-5% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this technology: (TITLE:"Allogeneic stem cell transplantation" OR ABSTRACT:"Allogeneic stem cell transplantation") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Allogeneic stem cell transplantation, not a curated reading list.

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