Alemtuzumab: Its Effects on Cell Transplantation in Immune Deficient Asian Patients

Allogeneic hematopoietic cell transplantation (HCT) serves as a widely recognized curative treatment option for patients suffering from inborn errors of immunity (IEI). This procedure requires the infusion of stem cells from a compatible donor to replace the compromised cells within the recipient's body. The strategy of reduced-toxicity conditioning (RTC) is employed to mitigate drug-related toxicities following HCT in patients with IEIs. Alemtuzumab, a humanized anti-CD52 monoclonal antibody, effectively inhibits the activity of immune cells and is used in conjunction with RTC treatment to enhance the acceptance of transplanted stem cells, thereby minimizing the risk of graft-versus-host disease (GVHD). While alemtuzumab is a well-known drug for RTC in Western nations, there is a limited clinical experience regarding its use in Asian patients with IEIs (1^✔ ✔Trusted Source
Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity

Go to source). A recent study released on May 22, 2024, in Volume 44 of the Journal of Clinical Immunology, conducted by researchers from Tokyo Medical and Dental University (TMDU) in Japan, aimed to bridge this knowledge gap.

Effects of Alemtuzumab on Asian Patients

The investigators performed a retrospective examination of Asian patients who received allogeneic HCT along with RTC using alemtuzumab, providing new insights into the effectiveness and constraints of this medication in an Asian population for the first time. They analyzed 19 patients who underwent their initial HCT conditioning with alemtuzumab at TMDU or collaborative facilities. The donors included HLA-half-matched parents, HLA-matched siblings, and unrelated donors. This patient group exhibited a variety of IEIs, such as chronic granulomatous disease, familial hemophagocytic lymphohistiocytosis, leukocyte adhesion deficiency, and X-linked lymphoproliferative syndrome. The broad spectrum of IEIs demonstrated the wide applications of alemtuzumab. Of the 19 patients, 18 survived throughout the 18-month median follow-up period, resulting in an impressive overall survival rate of 94.7% post-HCT.

Highlighting the efficacy demonstrated by alemtuzumab, senior author Prof. Hirokazu Kanegane shares, “All surviving patients recovered from the symptoms occurring from the original disease after HCT, including those with active hemophagocytic lymphohistiocytosis, which is life-threatening,”

Except for one patient who passed away, all other patients achieved high levels of neutrophil and platelet engraftment within three months. In other words, the precursors of these cells successfully made their way to the recipient’s bone marrow, where they managed to survive and multiply into healthy immune cells. However, there were notable variations in donor chimerism – the proportion of grafted donor cells found in the recipient’s body. It was found that six months to a year after HCT, six patients exhibited less than 80% of donor CD3+ T cells in their blood, implying that these immune cells were not as effectively replaced as the other types.

How Safe and Efficacious Is Alemtuzumab

Another important point to mention is that GVHD, which is a typical complication following allogeneic HCT, occurred in acute form in only eight patients and in chronic form in five. Fortunately, the acute GVHD never reached the most severe categories, and only two of those with chronic GVHD had to receive additional immunosuppressive therapy. Among other typical complications of HCT, viral infections were observed in 11 patients, with 6 of them showing a symptomatic infection- a higher frequency when compared with patients who didn’t receive alemtuzumab.

Overall, the researchers demonstrated that RTC with alemtuzumab was safe and effective in patients with IEIs. However, further investigation is necessary to make it even more safe and effective through optimized treatment and management protocols.

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“We need to carefully address the development of frequent viral infections and unstable levels of donor T-cell chimerism, emphasizing the importance of monitoring viral status and T-cell-specific chimerism in patients with IEIs treated with HCT using alemtuzumab. Moreover, the optimal dose of alemtuzumab should be further investigated in future prospective studies,” concludes lead author Dr. Satoshi Miyamoto.

We hope that this study paves the way for better and more reliable conditioning protocols involving alemtuzumab for patients with congenital immune disorders.

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Reference:

1. Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity - (https://link.springer.com/article/10.1007/s10875-024-01734-5)

Source-Medindia