Reduced-intensity conditioning reduces the risk of severe infections after allogeneic peripheral blood stem cell transplantation

Abstract

Summary:We compared the occurrence of severe infections following 71 reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and 123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA-identical siblings. The probability of 1-year infection-related mortality (IRM) was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On multivariate analysis the only significant variable associated with a higher risk of IRM was the development of moderate-to-severe GVHD (P = 0.005). The probability of developing CMV infection was 39% in the STAND group and 21% in the MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%, respectively (P = 0.05) (11% and 1%, respectively, in seropositive donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection identified four variables associated with a higher risk: CMV positive serostatus (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to-severe GVHD (P Ͻ 0.001) and a dose of CD34 + cells infused below 6 × 10 6 /kg (P = 0.01). Invasive fungal infections and pneumonias of unknown origin did not differ between groups, and neither did other severe non-CMV viral infections and bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease the risk of dying from an opportunistic infection and reduces the occurrence of CMV infection and disease. Overall, the development of GVHD (acute or chronic) is an important risk factor for these complications. Other infections continue to pose a significant threat to recipients of RIC allografts, stressing that prophylactic and supportive measures are an Following conventional allogeneic hematopoietic stem cell transplantation (HSCT) all patients experience a period of profound neutropenia and immunodeficiency that are significantly responsible for the serious infectious complications that ensue post transplant. Standard conditioning regimens for HSCT involve high-dose chemoradiotherapy given in doses that are myeloablative or at least severely myelotoxic. However, over the past years several groups of investigators have developed reduced-intensity conditioning (RIC) or non-myeloablative regimens, which lead to engraftment of donor lymphoid and hematopoietic stem cells without the extrahematologic toxicities of traditional myeloablative transplants. [1][2][3][4][5][6][7] This reduced extrahematologic toxicity may lead to a reduction in infectious complications post transplant, since disruption of the gastrointestinal mucosa and/or damage to other key organs is a significant triggering mechanism of many of the infections that occur post transplant. 8,9 On the other hand, graft-versus-host disease (GVHD) and its treatment has a profound negative impact on immune reconstitution following HSCT, 10 and the impact of RIC regimens on the risk of acute and chronic GVHD is currently uncertain. The potential benefit on the ri...

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

“…4,9,14,19,31,32 Several observations in this study support that CMV infection and disease are still a frequent and serious complication, with a significant incidence of CMV-D (11%), similar to that observed earlier in alloHSCT-RIC patients. 3,9,31 Of note, 48% of the cases of CMV-D occurred late post transplant (after day þ 100). In this study, we report a median onset of CMV-I of 57 days, which seems to be delayed compared with RIC regimens based on in vivo T-cell depletion.…”

“…This observation, in addition to the high rate of late (after day þ 100) episodes of CMV-I and CMV-D (63 and 48%, respectively) have substantial implications. First, patients conditioned without T-cell depletion are expected to have a high incidence of late CMV reactivations, 3 as a high incidence of moderate-to-severe GVHD occurs. It is well know that GVHD and its treatment are major risk factors for CMV disease.…”

“…Some authors have also described a reduction of incidence of cytomegalovirus infection (CMV-I) and disease (CMV-D) during the first months after transplant, but with later increases because of graft-vs-host disease (GVHD) and its treatment. 3 However, RIC regimens that include in vivo T-cell depletion with antithymocyte globulin (ATG), and, more importantly, with alemtuzumab, may lead to high incidence of CMV-I after HSCT, but CMV-D may be prevented with close monitorization and pre-emptive anti-CMV therapy. [4][5][6][7] On the other hand, non-T-cell depleted RIC regimens may lead to a high incidence of extensive chronic GVHD and, thus, potentially to a high risk of late (after 3-4 months post-HSCT) CMV-I and CMV-D.…”

Fewer infections and lower infection-related mortality following non-myeloablative versus myeloablative conditioning for allotransplantation of patients with lymphoma

“…[1][2][3][4][5] Infections are frequent complications following HSCT and vary widely with the donor type, conditioning regimen, the immunosuppressive therapy used to prevent and treat GVHD as well as host factors such as age, underlying malignancy and presence of comorbidities. [6][7][8][9][10][11][12] Non-myeloablative (NMA) conditioning has been explored to decrease acute toxicities and shorten neutropenia and yet maintain a GVL effect. [5][6][7][8][9][10][11][12][13][14][15][16] The wider use of NMA regimens allows patients with less than adequate organ function, preceding fungal infections, or older age to receive allografts.…”

“…The results of published analyses of infections following allografts vary widely and are largely limited to cohorts of patients with heterogeneous diseases. [7][8][9]11,12,16,17 We examined the differences in etiologies and timing of bacterial, viral and fungal infections and their risk factors in 141 patients with lymphoma after either NMA or MA conditioning allografts. 5 …”