Adenovirus is increasingly recognized as an important pathogen in stem cell transplant recipients, reflecting increased awareness about the virus, together with changes in transplant practice such as ...the performance of more high-risk transplants, and improvements in diagnostic methods. In retrospective studies, the reported incidence of adenovirus infections ranged between 4-20% with a similar variation in the proportion of patients developing invasive disease. In contrast, the incidence of adenovirus infection varies between 20-30% in recent prospective studies on T-cell depleted or mismatched allografts and about 30-40% of these patients develop invasive disease. These prospective studies have established a relationship between the risk of invasive adenovirus disease and a number of factors such as the extent of T-cell depletion, the intensity of immunosuppressive therapy and the kinetics of lymphocyte recovery post-transplant. Polymerase chain reaction (PCR) assays to detect adenovirus DNA in peripheral blood have shown a strong correlation between viremia and the risk of disseminated adenovirus disease. These developments have led to the possibility of a preemptive antiviral treatment strategy for asymptomatic adenovirus infections. In addition, a better understanding of the interactions between adenovirus and host immune system in the post-transplant setting might enable development of effective immunotherapeutic strategies against adenovirus infections.
The impact of newer approaches to haploidentical transplantation on Epstein-Barr virus (EBV) is largely unknown.
We prospectively evaluated the incidence of EBV reactivation and its impact on ...transplantation outcomes in 71 patients undergoing haploidentical transplantation with posttransplantation cyclophosphamide in combination with CTLA4Ig-based T-costimulation blockade.
Eight patients developed EBV reactivation at a median of 96 days with no incidence of lymphoproliferative disorder. There was no impact of EBV reactivation on acute graft-versus-host disease (GVHD), nonrelapse mortality, progression-free, or overall survival. Despite an overall incidence of 19%, there was a significant increase in chronic GVHD following EBV reactivation (62.5% versus 8%; P = 0.01). NKG2A subset of CD56 natural killer cells increased substantially and persisted following EBV reactivation and chronic GVHD, with a reciprocal decrease in NKG2C subset, whereas the reverse was witnessed in those without chronic GVHD (P < 0.01). Increase in NKG2C subset and a decrease in the NKG2A subset were witnessed within 3 months of subsidence of chronic GVHD.
Thus, CTLA4Ig-based haploidentical transplantation was associated with a low incidence of EBV reactivation without EBV-lymphoproliferative disorder. However, EBV reactivation was associated with a sustained alteration in NKG2A and NKG2C subsets of CD56 natural killer cells which might have a pathogenic role in chronic GVHD.
The management of myeloma has evolved dramatically in the last two decades. High dose melphalan and autologous hematopoietic stem cell transplantation (HSCT) marked the beginning of this journey. ...This was followed by an explosion of novel agents which were approved for management of myeloma. Allogeneic HSCT which was deemed as the only curative option was largely abhorred due to high transplant-related mortality (TRM) until the advent of reduced intensity conditioning (RIC). An approach of tandem autologous and RIC-allogeneic transplantations has showed the best promise for cure for this condition, particularly for those with high-risk cytogenetics. Yet, allogeneic HSCT seems to have fallen out of favor due to the projected high TRM and late relapses, even though the alternatives do not offer a cure, but merely prolong survival. Offering an allogeneic HSCT as a final resort in unlikely to yield gratifying results. At the same time, allogeneic HSCT needs to evolve in a disease-specific manner to address the relevant concerns regarding TRM and relapse. With the introduction of effective GVHD prophylaxis in the form of post-transplantation cyclophosphamide, transplantation from a haploidentical family donor has become a reality. The challenge lies in segregating graft-vs-myeloma effect from a graft-versus-host effect. We discuss the pro-survival and anti-apoptotic pathways via CD28-CD86 interactions which confer survival advantages to myeloma cells and the possibility of disruption of this pathway in the context of haploidentical transplantation through the use of CTLA4Ig without incurring T cell alloreactivity.
Herpes simplex virus (HSV) infections in 75 allogeneic stem cell transplant recipients were analyzed. Sixteen patients developed HSV disease following transplantation. The risk factors were age, sex ...(females), unrelated donor graft, and graft-versus-host disease (GVHD) grade ⩾2. Seven patients did not respond to acyclovir, and 3 patients failed to respond to foscarnet. Isolates from 4 patients developed resistance to acyclovir/penciclovir, and 3 patients had foscarnet-resistant isolates. The remaining 3 patients failed to respond to acyclovir, despite having sensitive isolates. All the isolates were sensitive to cidofovir, for which the IC50 values correlated inversely with those for acyclovir (P = .01). The risk factors for clinical resistance to antiviral drugs were a GVHD grade ⩾2 (P = .001) and the lack of ganciclovir prophylaxis (P = .01), with a higher nonrelapse mortality in the latter group (P < .0001). Clinical as well as in vitro resistance to antiviral drugs is common in patients with severe GVHD and is associated with a poor outcome.
We evaluated the incidences and consequences of rotavirus induced diarrhea in a cohort of 115 patients undergoing T‐cell replete haploidentical transplantation. Four out of 115 patients developed ...rotavirus‐induced diarrhea between 47 and 147 days. The incidence of rotavirus infection was 9.7% in children compared to none in adults (P = .01). This was 25.3% in those with GVHD compared to 1.2% in those without GVHD (P = .001). Rotavirus infection was followed by post–transplantation hemophagocytic syndrome (PTHPS) at a median of 4 days (range, 3‐10 days) in all four patients. Three patients succumbed to the complications related to PTHPS. Only one patient, who is long‐term survivor, was able to eliminate this virus after 2 weeks. Children undergoing T‐replete haploidentical hematopoietic cell transplantation who develop GVHD are at a higher risk of community‐acquired rotavirus infection which was strongly associated with PTHPS with poor outcome.
Highlights•CTLA4Ig-based conditioning in aggressive B-cell lymphomas is aimed at inducing apoptosis in tumor cells via its ligation with CD80. •Early and sequential CTLA4Ig-primed donor lymphocyte ...infusions administered after haploidentical HCT may promote mature NK cell proliferation. •Both CD80 expression on the tumor cells and proliferation of mature NK cells seemed to correlate with improved outcome with this approach.
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