Incidence and Outcome of Non-CMV Viral Infections in 202 Consecutive Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Recipients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1965-1965
Author(s):  
Christian Junghanss ◽  
Sebastian Rohde ◽  
Max Haversath ◽  
Guenther Kundt ◽  
Daniel Wolff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Fungal Infection ◽  
Viral Infections ◽  
Multivariate Analyses ◽  
Chronic Gvhd ◽  
Significant Risk ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Infection Diagnosis

Abstract Background: Viral infections contribute significantly to morbidity and mortality following allogeneic HSCT. Whereas incidences and risk factors for CMV infections are well studied data for other viral infections are more limited. Here, we present data on 202 alloHSCT recipients that received predominantly reduced intensity conditioning (RIC). Patients and Methods: Data of 202 consecutive patients (pts) who received HSCT during 1/1999 to 12/2006 were retrospectively analysed with regards to viral infections caused by adenovirus (AdV), herpes simplex virus (HSV), varicella zoster virus (VZV), human herpesvirus 6 (HHV6), epstein-barr virus (EBV) and BK-virus (BKV). Other factors included were gender, age, underlying disease, disease status, year of diagnosis, year of HSCT, time from diagnosis to HSCT, donor type, gender-matching between donor and recipient, stem cell source, conditioning-regimen, T-cell-depletion, prior autologous HSCT, acute and chronic GvHD, prior fungal infection, and viral serostatus of the recipients. Results: Median follow-up was 9.2mths (mean 21.7mths, range 8days to 95.3mths). Median pt. age was 45yrs (range 15 to 69yrs). Underlying diseases were ALL (n=20), AML (n=63), CLL (n=7), CML (n=32), MDS (n=21), MM (n=17), NHL (n=28), OMF (n=5), others (n=9). 137 pts received RIC most commonly based on treosulfan/fludarabine (n=112). 65 pts received myeloablative conditioning mainly based on 12Gy TBI containing regimen (n=48). GvHD-prophylaxis consisted of CSA/MTX (n=106), other CSA based regimen (n=83) or other (n=13). The overall infection incidences of AdV were 4.0%, of HSV 7.4%, of VZV 5.9%, of HHV6 8.9%, of EBV 4.5% and of BKV 5.4%. Median time of onset of AdV infections were 64 days after HSCT, of HSV 34 days, of VZV 542 days, of HHV6 97 days, of EBV 83 days, of BKV 50 days. Pts with AdV or HHV6 infections had a inferior survival compared to pts w/o the according viral infection (p=0.024 and p=0.048, respectively). 3/8 pts (37%) with AdV and 5/18 pts (28%) with HHV6 infections died within 30 days after infection diagnosis. Pts with EBV or BKV infections tended to have an inferior survival compared to pts w/o the according infection (p=0.084, p=0.152, respectively). 4/9 pts (44%) with EBV and 2/11 pts (18%) with BKV infection died within 30 days after infection diagnosis. Whereas pts with HSV infections had a similar survival compared to pts w/o infections, mean survival for pts with VZV infections was significantly better compared to pts w/o VZV infections (p=0.003). In multivariate analyses VZV infections remained to be associated with better survival (p=0.046, HR 0.132, CI 0.018–0.962). The other viral infections did not remain significant risk factors when analysed adjusted for competing risk factors. In order to determine the influence of late viral infections we performed an additional multivariate analyses solely including pts surviving beyond day 90. EBV infections (p=0.024, HR 2.807, CI 1.147–6.873) and HHV6 infections (p=0.013, HR 2.594, CI 1.227- 5.484) were significant risk factors for inferior survival besides unrelated donor HSCT (p=0.013), acute GvHD III/IV (p=0.001) and fungal infection prior to HSCT (p=0.005). Conclusion: Non-CMV viral infections are commonly observed following myeloablative and RIC alloHSCT. Since they are associated with significant mortality early broad viral screening seems advisable if virus infections are clinically suspected.

Higher Rate of Thrombotic Thrombocytopenic Pupura (TTP) Associated with Graft Versus Host Disease (GVHD) and Unrelated Donor Bone Marrow Transplantation (BMT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1111-1111
Author(s):  
B. Oran ◽  
A. Aleman ◽  
E. J. Shpall ◽  
C. Hosing ◽  
M. Korbling ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Stem Cell ◽  
Median Time ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Lymphoid Malignancies ◽  
Gvhd Prophylaxis

Abstract TTP is one of the complications of allogeneic hematopoietic stem cell transplantation (HSCT). In contrast to idiopathic cases, post-transplantation TTP may not be associated with severe von Willebrand factor-cleaving protease deficiency but rather a diffuse endothelial injury. Our aim was to define incidence, risk factors and mortality of TTP following allogeneic HSCT. 1312 patients with lymphoid malignancies (n=605), myeloid malignancies (n=688) or aplastic anemia (AA, n=18) who were treated with ablative preparative regimens (n=614) or reduced intensity regimens (n=697) followed by HSCT from an HLA matched related (MRD, n=694) or unrelated donor (MUD; n=461) and 1–3 antigen mismatched related (MMR, n=99) or unrelated donor (MMUD, n=57) between December 1997 and December 2004 were studied. Patients with prior allogeneic HSCT or graft failure were excluded. GVHD prophylaxis was tacrolimus-based in 1276 (97.3%) and cyclosporine based in 15 (1.1%) patients. Twenty patients did not receive GVHD prophylaxis per protocol. Anti-thymocyte-globulin (ATG) was added in 350 patients. Stem cell sources were bone marrow (n=626), peripheral blood (n=635) or cord blood (n=50). The following variables were evaluated: age, gender, primary diagnosis, disease status before HSCT, intensity of preparative regimen, stem cell source and acute GVHD(aGVHD) grade ≥2 (time dependent variable). Of the 1312 patients with a median follow-up from transplantation of 11.4 months (range, 5 days-7.2 years), 77 developed TTP (6%). The actuarial risk of developing TTP was 6.5% at 1 year. The median time of the onset of TTP was 67 days post HSCT (range, 11–1812) with 27 cases (35%) presenting after day 100. Female gender, lymphoid malignancies, unrelated or antigen mismatched related donor and aGVHD grade ≥2 were found to be independent risk factors. (Table1). Among the patients who had aGVHD grade≥2, the median time of interval between the onsets of two events was 25 days (range, 2–335 days). All patients were treated with therapeutic plasma exchange (PE). Of the 77 patients only 1 died of TTP (intracranial hemorrhage). The overall one-year survival after TTP was 29% and the most common cause of death were acute or chronic GVHD (n=35, 55%) and primary disease progression (n=10, 16%). Stem cell donors other than MRD, lymphoid malignancies and aGVHD≥2 have been established as risk factors associated with development of TTP and therapeutic PE has been shown to decrease TTP related mortality. Risk factors for TTP after allogeneic HSCT Variables sample size events HR 95% CI p Male 793 33 1.0 Female 518 44 2.2 1.3–3.6 0.002 Myleoid malignancy 688 33 1.0 Lymphoid malignancy 605 42 1.9 1.1–3.3 0.03 AA 18 2 1.3 0.2–8.0 0.75 MRD 694 28 1.0 MUD 461 40 2.9 1.6–5.1 <0.001 MMR 99 7 2.4 0.9–6.0 0.06 MMUD 57 2 1.7 0.4–7.6 0.5 aGVHD ≥2 370 39 3.3 2.0–5.5 <0.001

Incidence and Outcomes of Immune Thrombocytopenia (ITP) Following Hematopoietic Stem Cell Transplantation (HCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1316-1316
Author(s):  
Milena Elimelakh ◽  
Ted Eastlund ◽  
Mark Reding ◽  
Todd DeFor ◽  
Linda Burns
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Platelet Count ◽  
Cumulative Incidence ◽  
Viral Infections ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Disease Free

Abstract While thrombocytopenia is common following HCT, and has been associated with delayed engraftment, disease relapse, infections and drugs, autoantibody mediated ITP is rarely observed. In one series of non-Hodgkin’s lymphoma patients, development of ITP following autologous HCT (autoHCT) was associated with long-term disease free survival (Hequet et al. Bone Marrow Transplant2003; 32:89). Limited data is available on occurrence and prognosis of ITP following allogeneic HCT (alloHCT). Here we report the incidence and outcomes of ITP in 1700 adults who underwent autoHCT (n=749) and alloHCT (n=951) between January 1990 and December 2004. Of the alloHCT recipients, 531 patients received stem cells from a sibling donor (SD), 268 from an unrelated donor (URD), and in 147 patients umbilical cord blood (UCB) was used as the stem cell source. ITP was defined according to the American Society of Hematology guidelines for diagnosis of ITP (Ann Intern Med1997; 126:319). In addition, a confirmatory bone marrow examination demonstrating adequate megakaryocyte numbers and morphology and absence of CMV viremia were required. Patients receiving interferon therapy around the time of ITP diagnosis were excluded. Recovery from ITP was defined as a sustained increase in platelet count to 140 x 109/liter (l). Ten patients (median age 37 years [range 25–51]), including 7 alloHCT and 3 autoHCT recipients developed ITP at a median 15 months (range 4–76) post transplant, with an overall cumulative incidence of 0.8% at 5 years (95% confidence interval [CI] 0.3–1.6%). Of the alloHCT recipients, four patients received one or two antigen mismatched UCB HCT, two received matched HCT from an URD and one a SD HCT. The overall cumulative incidence of ITP at 5 years was highest among UCB HCT recipients (3%; 95% CI 0–6%) as compared to SD (0.2%; 95%CI 0–0.5%) and URD (0.7%; 95% CI 0–1.7%) HCT recipients (p<0.01). Nine (7 alloHCT and 2 autoHCT) recipients were transplanted for hematologic malignancy and one autoHCT patient for metastatic breast cancer. Nine of ten patients received myeloablative conditioning regimen. Six of the seven alloHCT recipients received cyclosporin for graft versus host disease (GVHD) prophylaxis. ITP was severe, with a nadir platelet count of 10 x 109/l in all patients. Platelet antibodies were present in 50% (3 of 6) of patients tested. Nine of the ten patients were in complete remission from their underlying malignancy at the time of ITP diagnosis. ITP was steroid refractory in the majority of patients, and required multiple treatment modalities. All alloHCT recipients with ITP developed chronic GVHD and systemic viral infections. While nine patients recovered, one autoHCT recipient died of multi-organ hemorrhage at 76 months post HCT. At a median follow-up of 61 months, seven patients are still alive and disease free, while two additional patients died (one from relapsed acute myeloid leukemia 32 months and one from pulmonary Aspergillosis 154 months post HCT). In summary, we found ITP to be a rare complication of HCT, with the highest incidence in recipients of UCB HCT. While the majority of patients eventually recovered from ITP and achieved long-term overall survival, the illness was severe, associated with chronic GVHD and serious viral infections. Degree of antigenic disparity, immune dysregulation, development of autoimmunity and its contribution to maintenance of disease control after transplantation may be implicated in pathogenesis of ITP following HCT.

scholarly journals Association of recipient and donor interleukin 6 polymorphisms 174 and 597 with outcome after allogeneic hematopoietic stem cell transplantation in children

2021 ◽  
Author(s):  
Laura Wetzel ◽  
Susan Wittig ◽  
Bernd Gruhn
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Interleukin 6 ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Significant Risk ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Purpose The success of allogeneic hematopoietic stem cell transplantation (HSCT) is compromised by complications such as infection, relapse, and graft-versus-host disease (GVHD). The investigation of non-HLA immunogenetics, particularly of cytokines, could identify predictors of an unfavorable outcome after allogeneic HSCT. In this study, we examined the impact of single nucleotide polymorphisms (SNPs) within the promoter region of interleukin 6 (IL6) on the development of GVHD after pediatric allogeneic HSCT. Methods In this retrospective analysis, we included 320 pediatric patients with a median age of 10 years who underwent an allogeneic HSCT and their respective donors. We used TaqMan real-time polymerase chain reaction to analyze the SNPs IL6-174 (G/C) and IL6-597 (G/A). The IL6-174 polymorphism was examined in 300 recipients and 295 donors. The IL6-597 polymorphism was analyzed in 299 recipients and 296 donors. We investigated the influence of the IL6-174 and IL6-597 polymorphisms on overall survival, event-free survival, relapse incidence, transplant-related mortality, and the occurrence of GVHD. Results G polymorphism at position 174 of the recipient IL6 gene was associated with a higher incidence of acute GVHD (GG vs. GC/CC; P = 0.024). Patients with IL6-597 GG genotype developed acute GVHD more frequently than individuals with an A allele (GG vs. GA vs. AA; P = 0.013). IL6-174 GG homozygous recipients had a more frequent occurrence of chronic GVHD (GG vs. GC/CC; P = 0.049). We observed a significant increased risk of chronic GVHD in recipients with IL6-597 GG genotype (GG vs. GA vs. AA; P = 0.043). Polymorphisms of donors did not affect the incidence of acute GVHD and chronic GVHD. In multivariate analysis, the IL6-174 and IL6-597 SNPs were independent significant risk factors for acute GVHD (P = 0.030; P = 0.007, respectively) as well as for chronic GVHD (P = 0.045; P = 0.015, respectively). In addition, older age at time of transplantation turned out to be a significant risk factor for chronic GVHD (P = 0.003). Conclusion Our study identified the IL6-174 and IL6-597 GG genotypes of pediatric allogeneic HSCT recipients as genetic risk factors for the development of acute GVHD and chronic GVHD. After evaluations in further studies, these findings could implicate the adjustment of prophylactic measures to reduce the occurrence of acute GVHD and chronic GVHD.

scholarly journals Association of Recipient and Donor Interleukin 6 Polymorphisms 174 and 597 With Outcome After Allogeneic Hematopoietic Stem Cell Transplantation in Children

2021 ◽  
Author(s):  
Laura Wetzel ◽  
Susan Wittig ◽  
Bernd Gruhn
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Interleukin 6 ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Significant Risk ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Purpose The success of allogeneic hematopoietic stem cell transplantation (HSCT) is compromised by complications such as infection, relapse, and graft-versus-host disease (GVHD). The investigation of non-HLA immunogenetics, particularly of cytokines, could identify predictors of an unfavorable outcome after allogeneic HSCT. In this study, we examined the impact of single nucleotide polymorphisms (SNPs) within the promotor region of interleukin 6 (IL6) on the development of GVHD after pediatric allogeneic HSCT. Methods In this retrospective analysis, we included 320 pediatric patients with a median age of 10 years who underwent an allogeneic HSCT and their respective donors. We used TaqMan real-time polymerase chain reaction to analyze the SNPs IL6-174 (G/C) and IL6-597 (G/A). The IL6-174 polymorphism was examined in 300 recipients and 295 donors. The IL6-597 polymorphism was analyzed in 299 recipients and 296 donors. We investigated the influence of the IL6-174 and IL6-597 polymorphisms on overall survival, event-free survival, relapse incidence, transplant-related mortality, and the occurrence of GVHD. Results GG polymorphism at position 174 of the recipient IL6 gene was associated with a higher incidence of acute GVHD (GG vs. GC/CC; P = 0.024). Patients with IL6-597 GG genotype developed acute GVHD more frequently than individuals with an A allele (GG vs. GA vs. AA; P = 0.013). IL6-174 GG homozygous recipients had a more frequent occurrence of chronic GVHD (GG vs. GC/CC; P = 0.049). We observed a significant increased risk of chronic GVHD in recipients with IL6-597 GG genotype (GG vs. GA vs. AA; P = 0.043). Polymorphisms of donors did not affect the incidence of acute GVHD and chronic GVHD. In multivariate analysis, the IL6-174 and IL6-597 SNPs were independent significant risk factors for acute GVHD (P = 0.030; P = 0.007, respectively) as well as for chronic GVHD (P = 0.045; P = 0.015, respectively). In addition, older age at time of transplantation turned out to be a significant risk factor for chronic GVHD (P = 0.003). Conclusion Our study identified the IL6-174 and IL6-597 GG genotypes of pediatric allogeneic HSCT recipients as genetic risk factors for the development of acute GVHD and chronic GVHD. After evaluations in further studies, these findings could implicate the adjustment of prophylactic measures to reduce the occurrence of acute GVHD and chronic GVHD.

Bronchiolitis Obliterans Following Unrelated-Donor Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4504-4504
Author(s):  
Liqun Zhou ◽  
Yi Luo ◽  
Yongxian Hu ◽  
Huarui Fu ◽  
Yamin Tan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Bronchiolitis Obliterans ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Management Approaches ◽  
Median Interval

Abstract Abstract 4504 Bronchiolitis obliterans (BO), occurring beyond 3 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been recognized as a late-onset noninfectious pulmonary complication associated with substantial morbidity and mortality. Some reports have described this complication with different incidence, associated risk factors, prognoses and therapeutic strategies. However, up to date, there is no unified understanding with respect to BO worldwide. In this study, we retrospectively analyzed the incidence, risk factors, clinical characteristics, management approaches and prognosis of BO among unrelated donor allo-HSCT recipients in our transplant center, aiming to improve cognition, reduce misdiagnose and dicrease motality in the future. Between June 2005 and May 2009, 117 patients underwent unrelated donor allo-HSCT while 98 patients who survived and were free of disease for more than 3 months after engraftment were enrolled. Myeloablative conditioning therapies for HLA-mathced transplant included busulfan-Cyclophosphamide (Bu-Cy) based regimens. In HLA-mismatched transplant, anti-thymocyte globulin (ATG) were added in addition to Bu-Cy based regimen. Patients were offered nonmyeloablative conditioning regimens when they were ineligible for myeloablative preparative regimens with fludarabine-based regimens including fludarabine, ATG and Bu. The diagnosis of BO was based on pulmonary function abnormalities, chest high-resolution CT (HRCT) findings and exclusion from respiratory infections. Management approaches for BO included immunosuppressive agents, azithromycin and symptomatic support. Some patients were further treated with etanercept (anti-tumour necrosis factor). In total 14 of the 98 patients (14.3%) developed BO at a median interval of 307.5 days post engraftment (range, 188–1316 days). Pulmonary function tests showed a decline in FEV1/FVC to a median interval of 0.51 (0.33-0.69) and FEV1 to 32% (17-46.2%) of predicted at BO diagnosis. Chest HRCT of BO patients showed areas of air trapping on expiratory views (71.4%), hyperinflation or bronchial dilatation (64.3%). All the 14 patients (100%) with BO complicated with chronic GVHD versus 41 of the 84 patients(48.6%) without BO (P<0.05). In total 1 of the 14 patients (7.1%) with BO underwent ATG-containing conditioning regimen versus 30 of 84 patients (35.7%) without BO (P<0.05). Multivariate analysis showed that primary disease type, donor and recipient's sex or age, stem cell type, myeloablative or nonmyeloablative conditioning regimen, aGVHD complication and HLA-disparities were not associated with the incidence of BO statistically. The prognoses of most BO patients were poor. In total only 4 of the 14 patients got improved and 3 were stable due to treatment while 2 were progressive and 5 (35.7%) died. Pulmonary failure was the leading cause of death for BO patients. In non-BO group, 23 of the 84 patients (28.6%) died, with a non-relapse mortality of 15.5% and infection became the leading cause of death. The non-relapse mortality in BO patients was higher than that in non-BO patients although there was no statistical significance (P>0.05). In all, our results demonstrated that chronic GVHD and conditioning regimen containing ATG, but not others which had been reported to be related with BO, were two risk factors associated with BO and the prognosis was extremely poor. More clinical trials and basic researches should be carried out to allow prospective identification of patients at greatest risk and early new therapeutic intervention to finally improve the survival of patients in this group. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Timing of allogeneic stem cell transplantation for myelodysplastic syndromes and aplastic anemia

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 77-81 ◽  
Author(s):  
Corey Cutler
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Significant Risk ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Matched Sibling ◽  
Disease Modifying ◽  
Disease Modifying Agents

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) is a potentially curative procedure, but is associated with a significant risk of morbidity and mortality. With the recent approval of disease-modifying agents, the appropriate timing of allogeneic HSCT needs to be addressed. Similarly, the optimal use of these disease-modifying agents before HSCT needs to be determined. In severe aplastic anemia, HSCT is a proven cure, but HLA-matched sibling donors are found in fewer than 25% of newly diagnosed patients. The use of early unrelated donor HSCT is an evolving concept that will become more accepted as improvements in HSCT outcomes continue.

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in the Treatment of Acute Lymphocytic Leukemia (ALL) in 126 Adults: Impact of Donor Source on Leukemia Free Survival (LFS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2064-2064 ◽  
Author(s):  
Priya Kumar ◽  
Todd E. Defor ◽  
Claudio Brunstein ◽  
Juliet Barker ◽  
John E. Wagner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Growth Factor ◽  
Disease Status ◽  
Lymphocytic Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Cell Source ◽  
Donor Source

Abstract White blood cell (WBC) count and specific cytogenetic abnormalities at diagnosis, patient age and disease status at HSCT have previously been identified as risk factors associated with LFS in patients with ALL. As the use of umbilical cord blood (UCB) is relatively new, particularly for adults, we sought to evaluate the relative impact of donor source. In this single center study, 126 adults aged 18–61 (median 31) years (yrs) underwent myeloablative conditioning (cyclophosphamide 120 mg/kg and total body irradiation 1320–1375 cGy based regimen in 92%) followed by allogeneic HSCT. Stem cell source was an HLA matched related donor (MRD) in 85, HLA matched unrelated donor (URD:M) in 15, HLA mismatched unrelated donor (URD:MM) in 14 and HLA 0–2 (A, B, DRB1) mismatched UCB in 12. At the time of HSCT, 64 patients were in CR1, 51 in CR2, and 11 patients in ≥ CR3; 20 pts had T-lineage disease; 38 pts (30%) had either t(9;22)(n=28), t(4;11) or t(1,19) (n=10) with the remainder (70%) having normal cytogenetics. WBC ≥ 30 x 109/l at diagnosis was documented in 50%. Demographics, disease characteristics at initial diagnosis and transplant variables were similar in all 4 groups except: year of transplant after 1996 and use of growth factor for all UCB recipients. Outcomes by donor source: MRD URD:M URD:MM UCB P N 85 15 14 12 Median follow up in yrs 9.3 3.5 7.2 1.2 OS 1 yr % (95% CI) 41 (31–52) 33 (9–57) 14 (0–33) 75 (51–100) 0.02 LFS 1 yr % (95% CI) 35 (25–45) 27 (4–49) 14 (0–33) 67 (40–93) 0.03 Relapse 1 yr % (95% CI) 21 (12–30) 20 (0–40) 0 8 (0–23) 0.22 TRM 1 yr % (95% CI) 44 (33–55) 53 (27–79) 86 (57–100) 25 (1–49) <0.01 As a consequence of low TRM, OS and LFS were superior after UCB transplants. In multiple regression analysis, 5 independent risk factors were significantly associated with poorer OS: use of URD:M (RR 3.8, 95% CI 1.1–13.8, p= 0.04) and URD:MM (RR 4.9, 95% CI, 1.3–19.1, p= 0.02), ≥ CR3 at HSCT (RR 3.0, 95% CI, 1.1–8.8, p= 0.04), WBC >30 x 109/l (RR 2.4, 95% CI, 1.4–4.1, p<0.01), cytomegalovirus (CMV) seropositive recipient and donor (RR 4.0, 95% CI, 2.0–7.9, p<0.01), and ≥ 2 induction regimens to achieve initial CR (RR 2.7, 95% CI, 1.2–5.9, p= 0.01). Patients who developed grade II–IV acute graft versus host disease (GVHD) had significantly lower mortality rates (RR 0.4, 95% CI, 0.2–0.7, p<0.01). There was no impact on OS by year of transplant or use of growth factor. Variables associated with poor LFS were identical to those for OS, and GVHD was again associated with improved LFS. These results support the use of UCB as an alternative stem cell source for adults with ALL with results comparable to outcomes observed with MRDs. In addition, GVHD is associated with improved LFS suggesting a significant graft versus leukemia effect with all donor graft sources.

Outcome of Patients Developing GVHD after DLI for CML Relapse from HLA-Identical Sibling or VUD HSCT.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1817-1817
Author(s):  
Yves Chalandon ◽  
Christoph Schmid ◽  
Kimmo Porkka ◽  
Alvaro Urbano-Ispizua ◽  
Bernd Hertenstein ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Chronic Gvhd ◽  
Median Number ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Initial Cell ◽  
Cell Dose ◽  
Stem Cell Source ◽  
Related Mortality

Abstract Using data submitted to the EBMT registry, we analyzed outcome on 344 patients (pts) who had received donor lymphocyte infusions (DLI) for relapse after allogeneic hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) in 31 centers. 113/344 pts (33%) developed acute graft-versus-host disease (aGVHD) a median of 50 days post DLI (max grade: I=42, II=30, III=31, IV=6)(60% grade II–IV). Organs involved (%): skin (88), liver (42), gut (30). Median age was 38 (4–59), 58% pts were male, 62 transplants were HLA-identical sibling and 51 unrelated. 74 were T-cell depleted, 92 transplanted in CP1, 21 beyond CP1. Relapse was molecular in 19 pts, cytogenetic in 31, hematological in 49, accelerated or blastic in 12. Median initial cell dose was 107CD3+ cells/kg (0.01–32), median number of DLI was 1 (1–10). aGvHD was treated with prednisone in 92% of pts, CSA in 52 %, ATG and monoclonal antibodies in 2% and other in 19%. aGVHD resolved in 53% of the pts within a median of 63 d (7–546). 82/344 pts (24%) had chronic GVHD (cGVHD)(30 limited, 50 extensive, 2 not specified), of those 46 (56%) following aGVHD post DLI. Organs involved (%): skin (75), liver (35), lungs (13), mouth (43), eyes (22) and gut (5). Median age was 35 (6–58), 51% were male, stem cell source was PB in 15% and marrow in 85%, 43 underwent HLA-identical sibling HSCT and 39 unrelated donor HSCT. Forty-three were T-cell depleted, 66 transplanted in CP1, 16 beyond CP1. Relapse was molecular in 21 pts, cytogenetic in 29, hematological in 22, accelerated or blastic in 7. Median initial cell dose was 107 CD3+ cells/kg (0.05–40), median number of DLI was 1 (1–7). 61 pts are alive with a median follow-up of 50 mth. Treatment was with steroids in 83% of pts, CSA in 58 %, MMF in 20%, thalidomide in 15%, photopheresis in 15%, PUVA in 10% and other in 17%. cGVHD resolved in 39% of the pts within a median of 354 d (44–1588). The estimated 5-y OS post-DLI was significantly lower in pts who developed aGVHD post-DLI, 61 ± 10% vs 74 ± 7% in the one that did not, p=0.007 and also a tendency to have a lower 5-y EFS, 58 ± 10% vs 65 ± 7%, p=0.19. Median duration of response to DLI in aGVHD pts was 4 y. aGVHD post-DLI did not influence the relapse rate (5 ± 5% vs 6 ± 5% in the absence of aGVHD). 5-y DLI related mortality was significantly higher in aGVHD pts, 31 ± 8% vs 4 ± 4%, p<0.00001. On the other hand, pts that developed cGVHD post-DLI had a tendency to have a better 5-y OS and EFS, 74 ± 11% and 71 ± 11% respectively vs 69 ± 6% and 62 ± 7% in those that did not, p=0.32 and 0.09. This was related to a tendency to lower incidence of relapse, 2 ± 3% in pts with cGVHD vs 9 ± 6% without, p=0.2. DLI related mortality was not different, 11 ± 8% vs 10 ± 5%, p=0.77. aGVHD post-DLI for CML relapse is mainly of advanced stage and negatively influence OS and EFS with a higher DLI related mortality. cGVHD post-DLI is mainly extensive, but pts with cGHVD tend to have better outcome with better 5-y OS, EFS and less relapse than those without, although this was not statistically significant.

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