A Comparison of Fungal Infections in Pediatric Bone Marrow Transplant Patients and Hematology and Oncology Patients at the Mattel Children??s Hospital at UCLA From 1991-2001 (original) (raw)
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Transplantation Proceedings, 2012
Introduction. Allogeneic hematopoietic stem cell transplantation is a curative modality for aplastic anemia; the preferred stem cell source is bone marrow. However, allogeneic peripheral blood stem cell transplantation (PBSCT) used in high-risk patients is associated with higher risk of chronic graft-versus-host disease (GVHD). Our center receives multitransfused, alloimmunized, infected, late referrals for transplant. Methods. Forty-one patients of median age 22 years (range 8 -37) received allogeneic-PBSCT from human leukocyte antigen (HLA)-matched sibling donors. The median time since diagnosis was 12 months (range 4 -65) and median pretransplant transfusions were 37 (range 6 -160). Six patients were platelet refractory and one alloimmunized for pan-red blood cell (RBC) antigens. Several patients had pretransplant icterus or renal dysfunction and 26 (63.4%) had unresponsive bacterial/fungal infections. Our conditioning regimen included fludarabine 30 mg/m 2 for 6 days (days -10 to -5), cyclophosphamide 60 mg/kg/d for 2 days (days -6 to -5), and antithymocyte globulin (ATGAM) 30 mg/kg/d for 4 days (day -4 to -1), which was reduced to 2 days in 2 patients. We used standard GVHD prophylaxis with cyclosporine and methotrexate on days 1, 3, 6, 11. Results. The median follow-up period was 29 months (range 6 -78) and median engraftment time 10 days (range 8 -17). Thirty-one patients (75.6%) were treated for infections, with 20 of these on antifungals for preexisting infections. There were two graft rejections and 10 (24.4%) deaths, with three intracranial hemorrhages, two rejections with infection, three cases of refractory GVHD (acute/overlap syndrome) with cytomegalovirus reactivation, and two invasive fungal infections. Overall incidence of acute GVHD was 39% with 2 grade IV cases. Ten (25%) cases developed chronic GVHD, with extensive GVHD in four. Conclusion. With more experience using shortened course of ATGAM, HLA-matched donor transfusions, and availability of newer antifungals, we have been able to decrease PBSCT-related mortality. Further improvement will be possible with early referrals. From the Departments of Hematology (T.S., P.S., V.S., P.M., M.M.) and Transplant Immunology and Immunogenetics (U.K.),
Bone Marrow Transplantation, 2014
for the Infectious/Non-infectious Complications Subcommittees of the Grupo Español de Trasplante Hematopoyético (GETH) Umbilical cord blood (CB) is increasingly used as an alternative source of stem cells in adult unrelated transplantation. Although registry studies report similar overall outcomes in comparison with BM/PB, comparative studies focusing on severe infections and infection-RM (IRM) with a long follow-up are scarce. A total of 434 consecutive unrelated transplants (1997-2009) were retrospectively analyzed to compare overall outcomes, incidence and risk factors of severe viral and invasive fungal infections in CB (n = 65) vs BM/PB recipients (n = 369). The 5-year OS was 38 vs 43%, respectively (P = 0.2). CB transplantation (CBT) was associated with a higher risk of invasive aspergillosis (100-days-cumulative incidence 16 vs 6%, P = 0.04) and CMV infection without differences in RM. No statistically significant differences were found regarding NRM (NRM of 38% in CB vs 37% in BM/PB at 1 year) nor IRM (30% in CB vs 27% in BM/PB at 1 year). In the overall population, NRM and IRM improved in more recent years. In adults who receive a single CBT, the risk of severe infections is increased when compared with unrelated BM/PB recipients, but mortality from infections is similar, leading to similar NRM and survival.
Biology of Blood and Marrow Transplantation, 2003
Peripheral blood hematopoietic stem cell (PBSC) transplants have been shown to result in more rapid engraftment than standard bone marrow transplants (BMTs). Little comparative data exist regarding complications in patients receiving transplants using these stem cell sources. In our study, 97 adults with advanced hematologic malignancies who received allogeneic PBSC transplants were compared with 97 adults who received allogeneic BMTs using identical preparative regimens and support parameters. The incidence of systemic infections and other major complications occurring within the first year after transplantation were calculated in both groups. Proportional hazard analysis was used to examine risk factors for death and complications in both groups. Patients receiving PBSC transplants had more rapid neutrophil (17 days versus 24 days; P < .001) and platelet engraftment (28 days versus 47 days; P < .001) than BMT recipients. The survival rate at 2 years was 38% in PBSC transplant recipients and 28% in marrow recipients (P ؍ .08). There was no difference in rates of grade II to IV acute graft-versus-host disease (GVHD) between groups (PBSC 46%, BMT 51%; P ؍ .3). PBSC transplant recipients were more likely to develop chronic GVHD after 180 days (hazard ratio 2.2; P ؍ .05). Accompanying this "late-onset chronic GVHD," a pattern of more frequent late systemic fungal and cytomegalovirus infections was observed in PBSC transplant recipients. In conclusion, although PBSC transplant recipients engraft more quickly than BMT recipients and have somewhat better 2-year survival rates, they develop more frequent late-onset chronic GVHD and may have more late fungal and cytomegalovirus infections than marrow recipients. Further studies must examine this late-onset chronic GVHD and better characterize immune reconstitution in PBSC transplant recipients to understand their effects on patient recovery.
Unrelated cord blood transplantation in children--a 10-year experience from UMMC
The Medical journal of Malaysia, 2009
Children who would benefit from a haematopoietic stem cell transplantation often lacked a compatible sibling donor. Unrelated cord blood transplantation was offered as an alternative donor source for patients with a variety of malignant and non-malignant diseases who had no further treatment options. Cord blood units were sourced from various international cord blood registries. The median nucleated and CD34+ cell doses were 8.7 x 10(7)/kg and 2.6 x 10(5)/kg respectively. In spite of adequate cell doses, a high rate of non-engraftment of 32% was observed. Acute graft-versus-host disease (GVHD) occurred in 14 out of the 15 patients who engrafted with 53% being grade III to IV GVHD. The five year disease free survival was 40.7% with infection and GVHD being the commonest causes of death. The five year disease free survival was 20.5% and 60.7% for malignant and non-malignant diseases respectively.
Biology of blood and …, 2006
We evaluated the occurrence of severe infections in 192 consecutive adult recipients of volunteer unrelated donor allogeneic hematopoietic stem cell transplants, with a detailed analysis of severe infections after receipt of cord blood transplants (CBTs; n ؍ 48) or bone marrow transplants (BMTs)/peripheral blood stem cell transplants (PBSCTs; n ؍ 144). At a 3-year median follow-up, CBT recipients had a higher risk of developing any severe infection (85% versus 69% in BMT/PBSCT recipients, P < .01). CBT recipients had a higher incidence of severe bacterial infections before day ؉100, but at 3 years the risks of these and other infections were similar in the CBT and BMT/PBSCT groups. In addition, the 100-day and 3-year incidences of infection-related mortality (IRM) did not differ between groups (P ؍ .2 and .5, respectively). In multivariate analysis, the most significant risk factor for IRM in all 192 patients was monocytopenia (.2 ؋ 10 9 /L). In CBT recipients, only neutropenia (.2 ؋ 10 9 /L) on day ؉30 and low nucleated cell dose infusion (<2 ؋ 10 7 /kg) showed a trend for increased IRM (P ؍ .05 in both cases). Stem cell source had no effect on day ؉100 or 3-year nonrelapse mortality (NRM), cytomegalovirus infection, cytomegalovirus disease (7% versus 6%), or overall survival (36% versus 39%, respectively). The number of mismatches in HLA (A, B, and DRB1) had no effect on any outcome in CBT recipients. In contrast, in the BMT/PBSCT group, the presence of any mismatch by low or high-resolution HLA typing (A, B, C, and DRB1) increased NRM and decreased overall survival (P < .01). IRM was the primary or secondary cause of death in 61% and 59% of CBT and BMT/PBSCT recipients who died, respectively. Our results confirm the relevance of severe infectious complications as source of severe morbidity and NRM after volunteer unrelated donor hematopoietic stem cell transplantation in adults, but suggest that CBT recipients have a similar risk of dying from an infection if an accurate selection of a cord blood unit is done.
Biology of Blood and Marrow Transplantation, 2006
We evaluated the occurrence of severe infections in 192 consecutive adult recipients of volunteer unrelated donor allogeneic hematopoietic stem cell transplants, with a detailed analysis of severe infections after receipt of cord blood transplants (CBTs; n = 48) or bone marrow transplants (BMTs)/peripheral blood stem cell transplants (PBSCTs; n = 144). At a 3-year median follow-up, CBT recipients had a higher risk of developing any severe infection (85% versus 69% in BMT/PBSCT recipients, P < .01). CBT recipients had a higher incidence of severe bacterial infections before day +100, but at 3 years the risks of these and other infections were similar in the CBT and BMT/PBSCT groups. In addition, the 100-day and 3-year incidences of infection-related mortality (IRM) did not differ between groups (P = .2 and .5, respectively). In multivariate analysis, the most significant risk factor for IRM in all 192 patients was monocytopenia (.2 × 109/L). In CBT recipients, only neutropenia (.2 × 109/L) on day +30 and low nucleated cell dose infusion (<2 × 107/kg) showed a trend for increased IRM (P = .05 in both cases). Stem cell source had no effect on day +100 or 3-year nonrelapse mortality (NRM), cytomegalovirus infection, cytomegalovirus disease (7% versus 6%), or overall survival (36% versus 39%, respectively). The number of mismatches in HLA (A, B, and DRB1) had no effect on any outcome in CBT recipients. In contrast, in the BMT/PBSCT group, the presence of any mismatch by low or high-resolution HLA typing (A, B, C, and DRB1) increased NRM and decreased overall survival (P < .01). IRM was the primary or secondary cause of death in 61% and 59% of CBT and BMT/PBSCT recipients who died, respectively. Our results confirm the relevance of severe infectious complications as source of severe morbidity and NRM after volunteer unrelated donor hematopoietic stem cell transplantation in adults, but suggest that CBT recipients have a similar risk of dying from an infection if an accurate selection of a cord blood unit is done.
Bone Marrow Transplantation, 2004
Cord blood (CB) is an alternative to other sources of stem cells for transplantation. However, the impact of including CB in the initial strategy of unrelated graft search in a cohort of patients has been the object of limited analysis. Here, we report the results of such a strategy in 91 consecutive children. Absence of mismatch was required for adult donors, and up to two mismatches were allowed for CB grafts, with a nucleated cell dose over 2.5 Â 10 7 cells/kg. A graft was found for 84 of the 85 children who remained available for a 3-month search. In all, 64 patients were transplanted, 36 with CB and 28 with bone marrow (BM). Primary graft failure, acute grade II-IV and extensive chronic graft-versus-host disease occurred in five, five and zero CB, and in three, one and two BM patients, respectively. The 3-year survival was 59% in CB and 57% in BM patients. Accepting CB as a source of stem cells offers a graft to almost every child in need of an unrelated transplantation, with a probability of survival similar to that of unrelated BM transplantation.