Cancer vaccine(Cosmo Pharmaceuticals NV)

Acute cardiac allograft rejection is a major cause of morbidity and mortality post-transplant. Total lymphoid irradiation (TLI) has been shown to cause long-lasting alterations in lymphocyte sub-sets, and thereby induces a state of partial response that is useful to prevent organ transplant rejection. In our previous report, treatment with TLI resulted in decreased episodes of acute rejection and steroid dosage requirements for up to 9.1 years post cardiac transplantation. In this study, we report an update on the short- and long-term effects of TLI in the treatment of cardiac transplant rejection.

We performed a retrospective analysis of patients with intractable cardiac allograft transplantation evaluated in the department of radiation oncology at our institution over 23 years (1998-2021). Cardiac allograft rejection was defined as multiple or persistent episodes of rejection despite aggressive immunosuppressive therapy. The prescribed dose was 8 Gy in 10 fractions to be delivered over 5 weeks. All episodes of pathologic acute cardiac rejection, duration of immunosuppression, and episodes of acute infection requiring treatment before and after TLI were documented. Overall survival (OS) was analyzed using Kaplan-Meier method. The median time to first cardiac allograft rejection and the median time to first acute rejection was monitored.

Of the 29 patients included, 21 (72.4%) had ISHLT grade 1R, 5 (17.2%), grade 2R, and 2(6.9%) grade 3R rejection. Rejection grade was unknown for 1 patient. The mean number of acute rejections after transplant was 14.4 episodes per patient (range 1-44) with median time to first rejection of 0.63 months. The median radiation dose was 8 Gy (range 7.2-8 Gy) delivered over a mean of 31 days. Treatment was stopped early in 2 (6.5%) patients (after 7.2 Gy and 7.9 Gy) for severe bone marrow suppression and drop in CD4 counts, respectively. The number of rejections dropped from 14.2 to 3.97 per patient over a median time of 29.0 months vs 28.1 months pre and post TLI (p = 0.01). The frequency of ISHLT acute grade 3R rejections decreased from 0.58 to 0.06 episodes per patient pre and post TLI (p = 0.02). Immunosuppressant requirements decreased from 2.83 before TLI to 2.69 after TLI (p = 0.71). Infection rates per patient were 0.71 pre TLI and remained at 0.63 post TLI. Treatment was well tolerated with 4 (13.8%) grade 2 or higher radiation toxicity. Median follow up was 76.3 months. Median and 3-year OS were 53.4 months and 60.9%, respectively.

TLI is a safe and effective treatment for control of intractable cardiac rejection. The episodes of acute rejection and immunosuppressant requirements are decreased, but with long-term follow up, these patients continue to experience rejection. However, TLI lowers the frequency of ISHLT moderate to severe rejection episodes for up to 6.4 years. There was no increased risk of severe infections and there were only minimal short- and long-term grade 2 or higher radiation toxicities.

The patient, a 56-year-old lady, also exhibited numerous lymphadenopathy, hepatosplenomegaly, hyperleukocytosis (167,200/µl, aberrant lymphocytes 91.5%), and fever. A lymph node biopsy revealed follicular lymphoma (FL), grade 1. Peripheral blood tumor cells did not express CD10, which was a distinctive characteristic of the lymph node specimen. To prevent tumor lysis syndrome (TLI), CHOP was delivered without an anti-CD20 antibody, but afterward, residual lymphoma cells were found in peripheral blood (>80%). As a result, obinutuzumab (Obi) was given on day 8 following the second round of CHOP, and the tumor cells in the peripheral blood vanished without any major side effects like TLI. She underwent six chemotherapy sessions before receiving maintenance therapy with Obi and achieving a full metabolic response. According to reports, leukemic FL exhibits negative CD10 expression in peripheral blood lymphoma cells, while leukemic mantle cell lymphoma also shows this trait. Therefore, it is important not to confuse the two types in diagnosis. Leukemic FL with significant leukocytosis is reportedly uncommon and has a bad prognosis. Our case indicates that CHOP with Obi would be a good alternative for cases like yours, however, there have been a few cases recorded. Further case accumulation or investigation is warranted.