Haematopoietic Stem Cell Transplantation

The answer first

Haematopoietic stem cell transplantation (HSCT) is the infusion of haematopoietic stem cells after high-dose chemotherapy (and sometimes radiotherapy) to rescue marrow function and, in allogeneic transplantation, to generate a new immune system that fights the underlying disease. It is offered for diseases where escalating chemotherapy doses can overcome resistance (autologous) or where a new immune system can eliminate residual disease (allogeneic). Two bedside rules change outcome: ^[1]

1. Autologous versus allogeneic is the single most important distinction. An autologous transplant uses the patient's own previously collected stem cells — there is no graft-versus-host disease (GVHD), transplant-related mortality is 1 to 2 per cent, and the graft-versus-leukaemia (GVL) effect is absent. An allogeneic transplant uses a donor's cells — there is a real risk of GVHD, mortality is 10 to 30 per cent, but the GVL effect can cure disease that chemotherapy alone cannot ^[8].
2. Complications follow a predictable timeline. The first 30 days are dominated by mucositis, neutropenic fever, veno-occlusive disease (sinusoidal obstruction syndrome) and haemorrhagic cystitis. Days 30 to 100 are dominated by acute GVHD, CMV reactivation and opportunistic infection. Beyond day 100 the patient enters the chronic phase, defined by chronic GVHD, secondary malignancy and endocrine late effects.

For autologous transplant the conditioning backbone is disease-specific: melphalan 200 mg/m2 for myeloma, BEAM (carmustine, etoposide, cytarabine, melphalan) for lymphoma. For allogeneic transplant the conditioning choice trades toxicity against relapse: myeloablative regimens are total body irradiation (TBI) plus cyclophosphamide, or busulfan plus cyclophosphamide or fludarabine ^[10]; reduced-intensity regimens are fludarabine plus lower-dose busulfan or melphalan, relying more on the GVL effect and suitable for older or comorbid patients.

Engraftment is defined as an absolute neutrophil count over 0.5 times 10 to the 9 per litre for three consecutive days, with platelet recovery over 20, typically 10 to 20 days after infusion. Engraftment failure, infection, GVHD and recurrence of the original disease are the dominant concerns in the first year. Long-term, the transplant survivor becomes a chronic-disease patient with endocrine, bone, malignancy and psychosocial needs. ^[1]

---

References10ShowHide

1. [1]Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease N Engl J Med, 2020.PMID 32320566
2. [2]Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease N Engl J Med, 2021.PMID 34260836
3. [3]Jagasia M, Perales MA, Schroeder MA, et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial Blood, 2020.PMID 32160294
4. [4]Richardson PG, Riches ML, Kernan NA, et al. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure Blood, 2016.PMID 26825712
5. [5]DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma Blood, 2009.PMID 19363221
6. [6]DiPersio JF, Micallef IN, Stiff PJ, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma J Clin Oncol, 2009.PMID 19720922
7. [7]Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease N Engl J Med, 2007.PMID 17251530
8. [8]McCurdy SR, Luznik L How we perform haploidentical stem cell transplantation with posttransplant cyclophosphamide Blood, 2019.PMID 31751485
9. [9]Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading Bone Marrow Transplant, 1995.PMID 7581076
10. [10]Russell JA, Tran HT, Quinlan D, et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes Biol Blood Marrow Transplant, 2002.PMID 12374451