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+ ...selection and T-cell add-back (TCAB), preceded by Campath-1H in vivo (CD34+/TCAB group, n=29), and the other using grafts incubated with Campath-1H in vitro (Campath-1H in vitro group, n=32). The probabilities of CMV reactivation and recurrence were 67 and 83.6% in the CD34+/TCAB group and 42.9 and 20% in the Campath-1H group (P=0.07 and 0.02). Donor sero-positivity reduced CMV reactivation in the Campath-1H group, but not in the CD34+/TCAB group. The durations of positive PCR/antigenemia positivity and antiviral therapy were also significantly longer in the CD34+/TCAB group. However, only two patients developed CMV disease in each group. The mean absolute lymphocyte counts (x 10(9)/l) at 30 days (0.27 vs 0.4, P=0.03) and 100 days (0.77 vs 1.4, P=0.01) were significantly lower in the CD34+/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 T-cell-depleted graft and a CMV sero-positive graft if possible.
Mixed chimerism after allogeneic bone marrow transplantation has been shown to cure a number of genetic disorders in both the clinical and experimental settings. Although encouraging results have ...been reported from animal experiments, the role of mixed chimerism in eliminating autoimmune disorders is not clear.
A 50-year-old man with extensive psoriasis received an allogeneic transplant from his brother after nonmyeloablative conditioning with fludarabine, melphalan, and Campath-1H for relapsed non-Hodgkin's lymphoma. The chimerism status and the immunological recovery after the transplant were serially monitored.
Twenty-one months after the transplant, the patient continues to be in complete remission from psoriasis and lymphoma with stable mixed chimerism (30% to 40% donor cells), despite significant recovery of T-cell subsets and antigen-specific response.
If mixed chimerism can be achieved safely with novel low-intensity conditioning regimens and results in sustained remission of autoimmune diseases, allogeneic transplantation may become a realistic therapy in the management of some patients with autoimmune disease.
The logistic difficulties of using fractionated total body irradiation (TBI) in the youngest children often limit the choice to single fraction TBI (sfTBI) or non-TBI-based regimens. We ...retrospectively evaluated 44 such children (<7 years) conditioned with either sfTBI (n=26) or busulphan-cyclophosphamide (Bu-Cy) (n=18), transplanted for hematological malignancies between 1988 and 2001. Both neutrophil and platelet engraftment were faster in the sfTBI group with a similar incidence of graft failure (6.8%). Acute GVHD (graft versus host disease) grade 2-4 occurred in 38.4% and 38.8% and chronic GVHD in 20% and 15.4% of the patients in the sfTBI and Bu-Cy groups, respectively. Grade 2-4 GVHD was associated with reduced risk of relapse (p=0.03). This finding was more pronounced in high-risk patients with 2/10 relapses in patients with GVHD grade 2-4, compared with 13/18 relapses among those with GVHD 0-1 (p=0.05). The probability of overall survival was 43.3% in the sfTBI group and 33.3% in the Bu-Cy group (p=0.6). However, the outcomes for high-risk patients and those with acute lymphoblastic leukemia were better in the sfTBI group. While hypothyroidism, growth hormone deficiency, learning problems and cataract formation were observed only in the sfTBI group, early cardiac toxicity, behavioral problems and seizures were more common in the Bu-Cy group. Thus, where fractionated TBI is not feasible, sfTBI offers improved survival in high-risk children with acute lymphoblastic leukemia compared with Bu-Cy, without an unacceptable increase in early or late toxicity.
Adenoviruses are emerging as a major cause of infectious complications after allogeneic transplantation. We evaluated the incidence and outcome of symptomatic adenovirus infection or adenovirus ...disease after alemtuzumab-based reduced-intensity conditioning in 86 consecutive patients. The overall probability of adenovirus disease was 18.4% (11/86 patients). Five patients died of progressive adenovirus disease, and this was the most important infectious cause of mortality in this cohort. The probability of nonrelapse mortality was 49% in patients with adenovirus disease compared with 25.5% in those without (
P = .007). The severity of lymphocytopenia and continuation of immunosuppressive therapy were the most important risk factors for progressive adenovirus disease and death. In contrast, patients who were not receiving immunosuppressive therapy or had had it reduced or withdrawn cleared the virus. We also detected a correlation between the lack of preemptive anti-cytomegalovirus (CMV) therapy for CMV reactivation and the risk of progressive adenovirus disease (
P = .05). Our findings highlight the emergence of adenovirus as an important posttransplantation pathogen even after reduced-intensity conditioning and demonstrate the effect of the severity of lymphocytopenia, anti-CMV prophylaxis, and immunosuppressive therapy on the outcome of adenovirus disease.
With improvements in the treatment of children with sickle cell disease (SCD), there has been a significant increase in the number of patients with SCD in adult hematology practice. Quality of life ...and life expectancy continue to be severely compromised in adult patients; hydroxyurea is the only treatment currently available that could reduce the severity and frequency of painful episodes. Allogeneic stem cell transplantation (SCT) has been offered to children with SCD as a curative option. We discuss the implications of new developments in the field of allogeneic SCT in the treatment of adult SCD patients in light of the experience derived from pediatric transplantation. These developments include innovations in the conditioning regimens, GVHD prophylaxis, and alternative donor SCT and their possible effect on adult SCD patients. Finally, we discuss a nonmyeloablative conditioning protocol for adult SCD patients and the eligibility criteria for adult SCD patients undergoing allogeneic transplantation.
PDF
