Influence of cytomegalovirus (CMV) sero-positivity on CMV infection, lymphocyte recovery and non-CMV infections following T-cell-depleted allogeneic stem cell transplantation: a comparison between two T-cell depletion regimens

Abstract

Summary:We compared the incidence and outcome of preemptively treated cytomegalovirus (CMV) infection, lymphocyte recovery and non-CMV infections between two different TCD modalities, one employing CD34 þ selection and Tcell add-back (TCAB), preceded by Campath-1H in vivo (CD34 þ /TCAB group, n ¼ 29), and the other using grafts incubated with Campath-1H in vitro (Campath-1H in vitro group, n ¼ 32). The probabilities of CMV reactivation and recurrence were 67 and 83.6% in the CD34 þ /TCAB group and 42.9 and 20% in the Campath-1H group (P ¼ 0.07 and 0.02). Donor seropositivity reduced CMV reactivation in the Campath-1H group, but not in the CD34 þ /TCAB group. The durations of positive PCR/antigenemia positivity and antiviral therapy were also significantly longer in the CD34 þ /TCAB group. However, only two patients developed CMV disease in each group. The mean absolute lymphocyte counts ( Â 10 9 /l) at 30 days (0.27 vs 0.4, P ¼ 0.03) and 100 days (0.77 vs 1.4, P ¼ 0.01) were significantly lower in the CD34 þ /TCAB group along with a higher incidence of non-CMV infections in CMV at-risk patients, but not in the CMV low-risk group. These findings suggest that the modality of TCD should be tailored according to the CMV risk status, and CMV sero-positive patients should receive a less extensively Tcell-depleted graft and a CMV sero-positive graft if possible.

Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis

“…22,23 However, reports that found age to be a significant risk factor for CMV infection included children, [3][4][5][6][7]25 where as our cohort comprised patients 18 years or older at the time of transplantation and age did not have an impact on CMV reactivation. 21 Methotrexate use had an increased adjusted HR of CMV reactivation in the main model, but it did not remain significant in the stringent model of persistent CMV positivity, whereas reduced-intensity conditioning became significantly protective for CMV reactivation in the stringent model.…”

“…1,2,13 The effect of CMV seropositivity of donor-recipient pairs, as well as that of acute graft-versus-host disease (GVHD) and its treatment, on the risk of CMV reactivation and disease after HSCT is well established. 3,4,[17][18][19][20] While the relative importance of different HSCT regimens on CMV infection, including nonmyeloablative or reduced-intensity conditioning, 21,22 T-cell depletion, 23,24 and donor relatedness 20,25,26 is established, the effect of GVHD prophylaxis strategies other than T-cell depletion has not been well studied.…”

Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism and survival

“…[24][25][26][27][28] However, the impact of different protocols on lymphoid depletion and recovery has not been properly evaluated, 29 although some differences in lymphocyte recovery have been noted. 25,26 We prospectively evaluated three different serotherapy schedules with a single prospective protocol on adjusted conditioning of 69 patients with a median age of 54 years, and mainly with high-risk hematological malignancies, in a single institution. Conditioning aimed to provide sustained antitumor activity with limited toxicity, and early establishment of a full donor chimerism for rapid achievement of the graft-versusmalignancy effect.…”

Prophylactic i.v. Igs in patients with a high risk for CMV after allo-SCT

“…Furthermore, protocol violations occurred in both the intervention and the control group, that is, some of the patients in the intervention group did not receive IVIG as scheduled by the algorithm and few patients of the control group received IVIG. Thus, we carried out a subanalysis evaluating patients of the intervention group who finally received at least three administrations of IVIG (median 4, range [3][4][5][6][7][8][9][10], and compared the results with those of patients of the control group who did not receive any IVIG. In this sub-analysis, the estimated cumulative incidence of CMV infection was also not decreased in the intervention group in comparison with the control group (58 and 43% 1 year after SCT).…”

“…6 Further risk factors for CMV infection in the early phase include the use of T-cell-depleted grafts, alemtuzumab or antithymocyte globulin as conditioning therapy or prophylaxis for acute GVHD. 7,8 Risk factors for CMV infection or disease in the late phase are predominately acute or chronic GVHD and CMV infection in the early phase. [1][2][3] Additionally, delayed immunological recovery of CMV-specific T cells, CD4 þ cells or NK (natural killer) cells has been found to be associated with a high risk for CMV infection early or late after allo-SCT.…”