ADVERTISEMENT

Improving Clinical Outcomes For Second Hematopoietic Stem Cell Transplants For Thalassemia Major

Allogeneic stem cell transplant is the only cure for β Thalassemia Major, but even with a matched sibling donor transplant, graft rejection is an unfortunate but all-too-common complication that may occur in up to 30% of transplants. This is especially true among patients older than 7 years of age and those with inadequate pre-transplant supportive care. Inadequate blood transfusions and sub-optimal iron chelation therapy can lead to iron overload-related end-organ damage. The liver is one the organs that is affected early and significantly by iron overload.

In addition to the risk of graft rejection, these high-risk patients and those having a second transplant are increasingly susceptible to toxicity secondary to the drugs used as part of the conditioning regimen, especially a form of hepatotoxicity called sinusoidal obstruction syndrome. The combination of these factors makes the utilization of drugs that have low hepatic toxicity and reduced regimen-related toxicities worth exploring in these groups of patients.

ADVERTISEMENT

Following an allogeneic stem cell transplantation graft rejection, either as primary graft failure (never engrafted or very early graft failure) or with a gradual drop in chimerism leading to secondary graft rejection and transfusion dependence, necessitates a second transplant. In cases where there is autologous recovery, either spontaneous or by re-infusion of banked autologous stem cells, the transplant may be deferred to allow organ recovery. However, in cases of rejection with aplasia (usually in primary graft rejection), a second transplant is considered urgent, to prevent complications secondary to aplasia.

Treosulfan an analog of busulfan has reduced hepatotoxicity and other regimen-related toxicity compared busulfan. Hence, treosulfan is an option worth considering to replace busulfan in the conditioning regimen for second transplants in patients with Thalassemia major.

We had earlier demonstrated that using this agent along with a peripheral blood stem cell graft significantly reduced the rate of graft rejection and improved the clinical outcomes of high-risk thalassemia undergoing an allogeneic stem cell transplant. There was no published data using this agent for conditioning in patients undergoing a second transplant in Thalassemia major. Here we report our experience in the management of graft rejection and the impact that a treosulfan-based myeloablative conditioning has had in this subset of patients.

We describe outcomes in 62 patients with Thalassemia Major who had graft rejection, of whom 32 had a primary graft rejection. Twenty-nine patients underwent a second transplant using the same donor. With the exception of one case, all the second transplants were done using the same donor as that used for the first transplant. Outcomes with different conditioning regimens were compared.

ADVERTISEMENT

Here we demonstrate a significantly superior clinical outcome in patients who had a second transplant using a Treosulfan-based myeloablative conditioning regimen along with a peripheral blood stem cell graft, with Thalassemia free and overall survival >80%, in comparison to other regimens (Figure 1).  In this series, graft-versus-host disease (GVHD) prophylaxis was modified, with omission of Day 11 methotrexate, in view of the high risk of rejection. Despite this modification, this incidence of GVHD was not higher than that seen with standard regimens.

A large percentage of patients in this study did not undergo a second allogeneic transplant. In this cohort of patients, all cases with aplasia had early mortality which was secondary to infections following the first transplant. Among those that had autologous recovery, all but three continue to be transfusion dependent. The reasons for deferral of transplant are not clear, due to the retrospective nature of the study, but our experience would suggest that the most common reason for deferral was the absence of financial resources to proceed with a second transplant. The infectious risks associated with transfusion, iron overload and challenges of adequate chelation are ongoing in this group.

This study demonstrates encouraging results that can be obtained following a second transplant using the same donor in patients with Thalassemia who have rejected the first graft after the use of treosulfan based myeloablative conditioning regimen and a peripheral blood stem cell graft source.

Figure 1: Comparison of overall survival between patients conditioned with Treosulfan-based MAC regimen versus others (Republished with permission from Vikram Mathews)

These findings are described in the article entitled Second Hematopoietic Stem Cell Transplant for Thalassemia Major: Improved Clinical Outcomes with a Treosulfan-Based Conditioning Regimen, recently published in the journal Biology of Blood and Marrow Transplantation. This work was conducted by Anu Korula, Nisham PM, Anup Devasia, Kavitha M. Lakshmi, Aby Abraham, Eunice Sindhuvi, Biju George, Alok Srivastava, and Vikram Mathews from Christian Medical College and Hospital.

ADVERTISEMENT

Comments

READ THIS NEXT

Solar Radiation Intermittency And PV System Performance

Almost all calculations involving solar radiation on the earth’s surface are currently carried out with integrated radiation values, such as […]

Let’s Get Radically Creative About Public Health And The Future

Like medicine, public health considers itself science-based. Although true in both cases, it is only a partial truth. Just as […]

Importance Of Surface Modification In Controllably Fabricating Highly Ordered Covalent Organic Frameworks (COFs)

Designing a highly ordered topological structure is an interesting methodology to explore new functional materials with fantastic physiochemical properties. Covalent […]

Scientists Create Enzyme Capable Of Eating And Breaking Down Plastic

Plastic pollution is a severe crisis plaguing much of the globe. A new enzyme created by a team of researchers […]

Fighting Atrial Fibrillation With Ice: Cryoballoon Ablation Best Practices Set Standards As Usage Expands

Atrial fibrillation, or AFib, is the most common heart rhythm abnormality. AFib occurs when the top chambers of the heart […]

An Ancient Carving Much Older Than The Pyramids Could Be Humanity’s First Depiction Of Evil Spirits

A recent study published in the journal Antiquity reports that a statue found in Siberia is likely more than twice […]

Exploring How An RNA-binding Protein Affects Stress-exposed Cells

Faced with sudden external physical stress, e.g.temperature shifts, desiccation, pH changes, cells need to adapt rapidly. Part of the adaptation […]

Science Trends is a popular source of science news and education around the world. We cover everything from solar power cell technology to climate change to cancer research. We help hundreds of thousands of people every month learn about the world we live in and the latest scientific breakthroughs. Want to know more?