Evidence Supports Early Referral for HSCT Against Higher-Risk MDS in Fit Older Adults

HOUSTON – Accumulating evidence supports early referral for allogeneic hematopoietic stem cell transplantation (HSCT) consultation so that transplant can be included as an integral part of the management plan in fit older adults with higher-risk myelodysplastic syndromes (MDS), according to a presentation at the 10th Annual Meeting of the Society of Hematologic Oncology (SOHO) by Ryotaro Nakamura, MD, of City of Hope in California.

“We found that among high-risk MDS patients aged 50 to 75 [years], having a suitable donor led to improved outcomes without disadvantage in quality of life,” Dr. Nakamura said during his presentation at SOHO. “And the message that we wanted to confer was that transplantation should be included as an integral part of this management class.”

Dr. Nakamura cited several lines of evidence from statical modeling analyses, prospective trials, and biologic donor assignment studies that suggest HSCT offers a benefit in overall survival and quality-adjusted survival.

“The number of HSCTs performed for MDS is increasing, according to the Center for International Blood and Marrow Transplant Research,” said Dr. Nakamura, “yet HSCT remains under-utilized for MDS.”

Dr. Nakamura noted that HSCT remains the only potentially curative therapy for MDS but is associated with significant risk of transplant-related mortality and morbidity. The risks of relapse and HSCT-related complications must therefore be weighed against the low survival rate without HSCT.

Dr. Nakamura said he often uses a blackjack analogy for considering the relative risks and benefits of transplant. “When I see a patient with high-risk MDS or leukemias, I feel like you’re dealing with a very strong card, and you’re stuck with a number 16, you know you have a high risk for going bust,” he said.

In blackjack “this decision-making is characterized mathematically,” Dr. Nakamura said, but when it comes to making a decision about a transplant, it’s “not that simple.”

This requires a complex and highly individualized decision process that incorporates careful risk stratifications for patient-, disease-, and transplant-related factors in a dynamic fashion.

“There are multiple different tools to risk stratify, including molecular landscapes, patient risks, and enhancing donor types, [and] also [to] improve the access and outcome of transplantation,” he said.

In a decision flowchart, Dr. Nakamura suggested that HSCT referral may be appropriate in certain cases of higher-risk MDS (eg, Revised International Prognostic Symptom Score, somatic mutations, symptomatic cytopenia, etc.) where the risk stratification of the patient suggests that the patient is fit as a transplant candidate. In other cases, non-HSCT therapy should be pursued depending on the disease response.

“Emerging non-HSCT therapy options as well as improving HSCT care will likely change the risk-benefit estimates over time, requiring continued review of evidence and patient-centered discussions,” Dr. Nakamura noted.

Reference

Nakumara R. Transplant in MDS. Abstract #EXABS-142-MDS. Presented at the 2022 Society of Hematologic Oncology (SOHO) Annual Meeting, September 28-October 1, 2022.