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Non-myeloablative conditioning for hemopoietic stem cell transplantation--does it work?

Cheong SK, Eow GI, Leong CF

Malays J Pathol, 2002 Jun;24(1):1-8.
PMID: 16329549

Allogeneic bone marrow or peripheral blood stem cell transplantation traditionally uses myeloablative regimen for conditioning to enable grafting of donor's stem cells. Animal experiments have shown that a milder non-myeloablative conditioning regimen does allow engraftment to occur. Nonmyeloablative conditioning regimens are low-intensity immunosuppressive treatment given to the recipient before infusion of donor's stem cells. It was reported to have decreased immediate procedural mortality, in particular those secondary to acute graft versus host reaction. However, it did give rise to higher risks of graft rejection, tumour tolerance and disease progression. Fortunately, appropriately administered donor lymphocyte infusion has been shown to establish full donor chimerism (complete donor stem cell grafting in the recipient's bone marrow) and potentiate antitumour effect (graft versus tumour reaction). The reduction of immediate transplant mortality allows the procedure to be carried out in older age groups, patients with concomitant diseases that otherwise would have made the patients unfit for the procedure, patients with non-malignant disorders such as congenital immune deficiencies, autoimmune disorders or thalassaemia majors. The regimen also allows transplantation of genetically manipulated haemopoietic stem cells (gene thrapy) to be carried out more readily in the immediate future. Lastly, the regimen may serve as a platform for immunotherapy using specific T cell clones for anti-tumour therapy with or without the knowledge of known tumour antigen.

Matched MeSH terms: Graft vs Host Disease/prevention & control
Fulltext Gamma irradiation and red cell haemolysis: a study at the Universiti Kebangsaan Malaysia Medical Centre

Yousuf R, Mobin MH, Leong CF

Malays J Pathol, 2015 Aug;37(2):91-4.
PMID: 26277664 MyJurnal

Gamma-irradiation of blood components is regarded a safe procedure used for prevention of transfusion associated graft-versus-host disease. However, reports showed that irradiation can cause erythrocyte haemolysis and damage to the RBC membrane. In University Kebangsaan Malaysia Medical Centre (UKMMC), a number of suspected transfusion reactions (TR) featured unusual isolated episodes of red-coloured-urine or haemoglobinuria among paediatric patients without clinical features of acute haemolytic TR. Haemolysis of irradiated red cells was suspected as a cause. This study was conducted to evaluate haemolytic changes of RBC components following irradiation. A prospective, pre- and post- irradiation comparative study was conducted on 36 paired RBC-components in the blood-bank, UKMMC in the year 2013. Samples were tested for plasma-Hb, percent-haemolysis, plasma-potassium (K⁺) and lactate dehydrogenase (LDH) level. Post-irradiation mean plasma-Hb and percent-haemolysis were significantly higher than pre-irradiation values at 0.09 ±0.06g/dl VS 0.10 ± 0.06g/dl and 0.19 ± 0.13% VS 0.22 ± .13% respectively, while plasma-K⁺ and LDH values did not show significant difference. However, the mean percent-haemolysis level was still within recommended acceptable levels for clinical use, supporting that irradiated RBC units were safe and of acceptable quality for transfusion. There was no conclusive reason for isolated haemoglobinuria following transfusion of irradiated red-cell products. Further research is suggested to investigate the other possible causes.

Matched MeSH terms: Graft vs Host Disease/prevention & control*
Is it time to reconsider prophylactic antimicrobial use for hematopoietic stem cell transplantation? a narrative review of antimicrobials in stem cell transplantation

Jahan D, Peile E, Sheikh MA, Islam S, Parasnath S, Sharma P, et al.

Expert Rev Anti Infect Ther, 2021 10;19(10):1259-1280.
PMID: 33711240 DOI: 10.1080/14787210.2021.1902304

INTRODUCTION: Hematopoietic Stem Cell Transplantation (HSCT) is a life-saving procedure for multiple types of hematological cancer, autoimmune diseases, and genetic-linked metabolic diseases in humans. Recipients of HSCT transplant are at high risk of microbial infections that significantly correlate with the presence of graft-versus-host disease (GVHD) and the degree of immunosuppression. Infection in HSCT patients is a leading cause of life-threatening complications and mortality.
AREAS COVERED: This review covers issues pertinent to infection in the HSCT patient, including bacterial and viral infection; strategies to reduce GVHD; infection patterns; resistance and treatment options; adverse drug reactions to antimicrobials, problems of antimicrobial resistance; perturbation of the microbiome; the role of prebiotics, probiotics, and antimicrobial peptides. We highlight potential strategies to minimize the use of antimicrobials.
EXPERT OPINION: Measures to control infection and its transmission remain significant HSCT management policy and planning issues. Transplant centers need to consider carefully prophylactic use of antimicrobials for neutropenic patients. The judicious use of appropriate antimicrobials remains a crucial part of the treatment protocol. However, antimicrobials' adverse effects cause microbiome diversity and dysbiosis and have been shown to increase morbidity and mortality.

Matched MeSH terms: Graft vs Host Disease/prevention & control*
Fulltext Treosulfan and Fludarabine Conditioning for Hematopoietic Stem Cell Transplantation in Children with Primary Immunodeficiency: UK Experience

Slatter MA, Rao K, Abd Hamid IJ, Nademi Z, Chiesa R, Elfeky R, et al.

Biol. Blood Marrow Transplant., 2018 03;24(3):529-536.
PMID: 29155317 DOI: 10.1016/j.bbmt.2017.11.009

We previously published results for 70 children who received conditioning with treosulfan and cyclophosphamide (n = 30) or fludarabine (n = 40) before undergoing hematopoietic stem cell transplantation (HSCT) for primary immunodeficiency (PID). Toxicity was lower and T cell chimerism was better in the patients receiving fludarabine, but cohort numbers were relatively small and follow-up was short. Here we report outcomes of 160 children who received homogeneous conditioning with treosulfan, fludarabine, and, in most cases, alemtuzumab (n = 124). The median age at transplantation was 1.36 years (range, .09 to 18.25 years). Donors included 73 matched unrelated, 54 1 to 3 antigen-mismatched unrelated, 12 matched sibling, 17 other matched family, and 4 haploidentical donors. Stem cell source was peripheral blood stem cells (PBSCs) in 70, bone marrow in 49, and cord blood in 41. Median duration of follow-up was 4.3 years (range, .8 to 9.4 years). Overall survival was 83%. No patients had veno-occlusive disease. Seventy-four patients (46%) had acute GVHD, but only 14 (9%) greater than grade II. Four patients underwent successful retransplantation for graft loss or poor immune reconstitution. Another patient experienced graft rejection and died. There was no association between T cell chimerism >95% and stem cell source, but a significant association was seen between myeloid chimerism >95% and use of PBSCs without an increased risk of significant GVHD compared with other sources. All 11 patients with severe combined immunodeficiency diagnosed at birth were alive at up to 8.7 years of follow-up. Long-term studies are needed to determine late gonadotoxic effects, and pharmacokinetic studies are needed to identify whether specific targeting is advantageous. The combination of treosulfan, fludarabine, and alemtuzumab is associated with excellent results in HSCT for PID.

Matched MeSH terms: Graft vs Host Disease/prevention & control
Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis

Shahnaz Syed Abd Kadir S, Christopeit M, Wulf G, Wagner E, Bornhauser M, Schroeder T, et al.

Eur J Haematol, 2018 Sep;101(3):305-317.
PMID: 29791053 DOI: 10.1111/ejh.13099

INTRODUCTION: Ruxolitinib is the first approved drug for treatment of myelofibrosis, but its impact of outcome after allogeneic stem cell transplantation (ASCT) is unknown.
PATIENTS AND METHODS: We reported on 159 myelofibrosis patients (pts) with a median age of 59 years (r: 28-74) who received reduced intensity ASCT between 2000 and 2015 in eight German centers from related (n = 23), matched (n = 86) or mismatched (n = 50) unrelated donors. Forty-six (29%) patients received ruxolitinib at any time point prior to ASCT. The median daily dose of ruxolitinib was 30 mg (range 10-40 mg) and the median duration of treatment was 4.9 months (range 0.4-39.1 months).
RESULTS: Primary graft failure was seen in 2 pts (4%) in the ruxolitinib and 3 (2%) in the non-ruxolitinib group. Engraftment and incidence of acute GVHD grade II to IV and III/IV did not differ between groups (37% vs 39% and 19% vs 28%, respectively), nor did the non-relapse mortality at 2 years (23% vs 23%). A trend for lower risk of relapse was seen in the ruxolitinib group (9% vs 17%, P = .2), resulting in a similar 2 year DFS and OS (68% vs 60% and 73% vs 70%, respectively). No difference in any outcome variable could be seen between ruxolitinib responders and those who failed or lost response to ruxolitinib.
CONCLUSIONS: These results suggest that ruxolitinib pretreatment in myelofibrosis patient does not negatively influence outcome after allogeneic stem cell transplantation.
Study site: 8 health clinics in Germany

Matched MeSH terms: Graft vs Host Disease/prevention & control