Reconstitution of the cellular immune response after autologous peripheral blood stem cell transplantation in patients with non‐Hodgkin's lymphoma

Abstract

Peripheral blood stem cell (PBSC) transplants may be depleted of lymphoid progenitors, thereby disabling the cellular immune response against viral pathogens after autologous PBSC transplantation (PBSCT). To monitor the cellular immune reconstitution after autologous PBSCT, we investigated the cytolytic activity (CLA) of peripheral blood T lymphocytes against Epstein-Barr virus (EBV) in 13 patients with non-Hodgkin's lymphoma or multiple myeloma. The individual EBV-directed CLA (EBV-CLA) was determined by calculating the number of cytolytic effector cells in 106 T cells needed to lyse 25% of autologous EBV-transformed B-lymphoblastoid cells, expressed as lytic units (LU25). During the first 6 months after PBSCT, the EBV-CLA was only 14.6% of the response of healthy controls (median 4. 8 vs. 32.9 LU25). Thereafter, the EBV-CLA increased to 28.15 LU25 (median) or 86% of healthy controls. Monthly follow-up analyses in five selected patients showed that the EBV-CLA was barely detectable at 4 weeks and recovered at 8-12 weeks after PBSCT in four out of five patients. Effector cells consisted mostly of CD8-positive T lymphocytes, with small CD4- and CD3/CD56-positive lymphocyte fractions. These results suggest that the reconstitution of the cellular immune response against EBV takes 8-12 weeks after autologous PBSCT.

Hepatitis B reactivation in multiple myeloma patients with resolved hepatitis B undergoing chemotherapy

“…Mya et al demonstrated that HBV reactivated at 3-5 months post-transplant (26). Interestingly, based on immune reconstitution reports on patients treated with ASCT, this is the time of recovery of cellular immunity after ASCT (27)(28)(29). In our series, 12 patients with HBV reactivation, reactivation occurred within 6 months of HDT/ASCT.…”

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

“…To test the approach of TCR genetic engineering of HSCs in the clinic, we designed a clinical trial of double cell therapy coadministering HSCs and T cells both genetically modified to express an NY-ESO-1 TCR. We propose to use 2 TCR-engineered cell therapies because we anticipate that the TCR-engineered HSCs will endogenously differentiate into fully active mature T cells with a long delay in their appearance in the periphery, as new T cells reaching peripheral circulation must undergo a thymic selection process which takes 1 to 3 months (20,21). In this clinical trial, TCR-engineered mature lymphocytes and TCRengineered HSCs will be coadministered to patients with NY-ESO-1-positive advanced cancers after a myelo-and lymphodepleting conditioning regimen.…”