June 16, 2016
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Autologous HSCT safe for patients with HIV–related lymphoma

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Patients with HIV–related lymphoma who meet standard transplant criteria can be safely considered for autologous hematopoietic stem cell transplantation, according to phase 2 study results published in Blood.

Autologous HSCT serves as the standard of care for patients with relapsed and treatment-resistant lymphomas. However, clinicians have been hesitant to offer the procedure to patients with HIV, for fear that their immune systems would not effectively recover after the administration of intense chemotherapy regimens or that patients might experience excessive toxicities after transplantation.

Joseph Alvarnas

Joseph C. Alvarnas

“These findings are remarkably important for a group of patients who, up until now, have been inconsistently treated,” Joseph C. Alvarnas, MD, clinical associate professor in the department of hematology and director of value-based analytics at City of Hope Comprehensive Cancer Center, said in a press release. “Based on our data, autologous stem cell transplant should be considered the standard of care for patients with HIV–related lymphomas for the same indications and under the same circumstances that we would use it in patients without HIV infection.”

Alvarnas and colleagues conducted a multicenter study including data from 40 patients (median age, 46.9 years; range, 22.5-62.2) with treatable HIV–related lymphoma. Thirty-five patients were men, and 80% (n = 32) had an undetectable HIV viral load (median, 80 copies/mL; range, 50-17,455) prior to transplantation.

The patients received a chemotherapy regimen of carmustine, etoposide, cytarabine and melphalan prior to transplantation, as well as consistent management of peritransplant antiretroviral treatment.

Median CD4–positive T-cell count prior to transplant was 249/L (range, 39-797).

OS at 1 year served as the primary endpoint.

Median follow-up was 24.8 months (range, 2.8-27.7).

The cohort had a 1-year OS probability of 87.3% (95% CI, 72.1-94.5) and a 2-year OS probability of 82% (95% CI, 65.9-91).

At the time of transplantation, 30 patients (75%) achieved complete remission, nine patients (22.5%) achieved partial remission and one patient with disseminated Hodgkin lymphoma experienced progression in a single nodal site.

After 100 days, 36 patients (92.3%) were in complete remission, with one patient in partial remission. Two patients had relapsed or progressive disease, and one patient died.

The 2-year PFS probability of the cohort was 79.8% (95% CI, 63.7-89.4), with a cumulative incidence of relapse or progression of 12.5% (95% CI, 4.5-24.8). Six patients relapsed or experienced progressive disease, four of whom died.

Causes of death within the first year after transplantation included relapsed or progressive disease (n = 3), organ failure (n = 1) and fungal infection (n = 1). Two patients died after 1 year, due to progressive disease (n = 1) and organ failure (n = 1).

OS and PFS probabilities did not differ between patients with Hodgkin lymphoma and non-Hodgkin lymphoma.

The cohort had a median time to posttransplant neutrophil recovery of 11 days, with a cumulative incidence of neutrophil recovery of 97.5% (95% CI, 77.7-99.7) by day 28. One patient died prior to achieving platelet recovery.

The median time to platelet recovery was 18 days, with a cumulative incidence of platelet recovery of 92.5% (95% CI, 75.9-97.8) by day 100.

Of 31 evaluable patients, 23 (74.2%) achieved recovery of hematological function at 1 year.

Fifty-five percent of patients (n = 22) experienced at least one infection within 1 year of transplant, 11 of whom had severe infections.

Nine patients experienced 13 unexpected grade 3 or higher adverse events (grade 3, n = 10; grade 4, n = 3), including infection or sepsis (n = 5), venous thromboembolism (n = 2), esophageal candidiasis (n = 1), enteritis (n = 1), hyperglycemia (n = 1), hypernatremia (n = 1), acute appendicitis (n = 1) and acute coronary syndrome (n = 1).

Sixteen patients required hospital readmission following initial transplant, including three patients who were readmitted four or more times.

The cohort had a median CD4–positive T-cell count of 280.3 (range, 28.8-1,148) 1 year after transplantation, and 82.6% of patients had an undetectable viral load.

“When you look at people’s recovery — recovery of their T cells and CD4 and suppression of viral load — we don’t see people losing control of HIV infection, nor do they have evidence of additional surgical deficits following transplant,” Alvarnas said. “I think that is very reassuring.”

The researchers compared outcomes of patients enrolled in this study with 151 matched, HIV–free controls identified through the Center for International Bone Marrow Transplant Research database and found no significant differences in 1-year OS (87.7%) or PFS (69.5%) probabilities.

“This is an important study because we need to better understand the long-term effects of HIV infection to ensure that patients are equitably treated in a way that respects their medical regimens and the biology of their HIV infection,” Alvarnas said. – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.