scholarly journals CD34+ Selected Ex-Vivo T-Cell Depleted (TCD) Grafts for Allogeneic Hematopoietic Cell Transplantation (Allo-HSCT) Is Associated with Low Incidence of Acute and Chronic Graft-Versus-Host Disease (GVHD) and High Chronic-Gvhd/Relapse-Free Survival

2016 ◽  
Vol 22 (3) ◽  
pp. S389
Author(s):  
Pere Barba ◽  
Patrick Hilden ◽  
Sean M. Devlin ◽  
Molly Maloy ◽  
Cristi Ciolino ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Ex Vivo ◽  
Chronic Gvhd ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Graft Versus Host ◽  
Low Incidence

scholarly journals Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation

Blood ◽  
2015 ◽  
Vol 125 (8) ◽  
pp. 1333-1338 ◽  
Author(s):  
Shernan G. Holtan ◽  
Todd E. DeFor ◽  
Aleksandr Lazaryan ◽  
Nelli Bejanyan ◽  
Mukta Arora ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Graft Versus Host ◽  
End Point ◽  
Key Points ◽  
Matched Sibling ◽  
Disease Free

Key Points GRFS is a new composite end point useful for comparing HCT techniques and represents ideal post-HCT recovery. In our cohort of 907 allogeneic HCT recipients, 1-year GRFS was 31%, with best outcomes in recipients of marrow from matched sibling donors.

scholarly journals Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT

2020 ◽  
Vol 38 (18) ◽  
pp. 2062-2076 ◽  
Author(s):  
Rohtesh S. Mehta ◽  
Shernan G. Holtan ◽  
Tao Wang ◽  
Michael T. Hemmer ◽  
Stephen R. Spellman ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Pairwise Comparison ◽  
Unrelated Donor ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Graft Versus Host ◽  
Alternative Donor

PURPOSE There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]–bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. METHODS We report composite end points of graft-versus-host disease (GVHD)–free relapse-free survival (GRFS) and chronic GVHD (cGVHD)–free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. RESULTS In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. CONCLUSION Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.

Serious Acute or Chronic Graft-Versus-Host Disease after Hematopoietic Cell Transplantation: A Comparison of Myeloablative and Non-Myeloablative Conditioning Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 755-755
Author(s):  
Olga Sala-Torra ◽  
Paul J. Martin ◽  
Barry Storer ◽  
Mohamed Sorror ◽  
Rainer F. Storb ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Hematopoietic Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Co Morbidity

Abstract We have previously described serious graft-versus-host disease (GVHD) as a highly undesirable outcome after allogeneic hematopoietic cell transplantation (HCT). Serious GVHD encompasses death, lengthy hospitalization, major disability, or recurrent major infections related to either acute or chronic GVHD. In a previous study, we found a 25% incidence of serious GVHD among 171 consecutive patients who had HCT after non-myeloablative (NMA) conditioning between January 1998 and May 2002. To put this observation into perspective, we applied the same criteria for serious GVHD in a cohort of 264 consecutive patients who had HCT after myeloablative (MA) conditioning during the same period of time and compared results with those of the previous study. The overall incidence of serious GVHD was 17% (44/264) in the MA group, compared to 25% (43/171) in the NMA group. There were no statistically significant differences in the incidence of grades III–IV GVHD, extensive chronic GVHD or nonrelapse mortality between the two groups (Table). Patients in the NMA group were older and had higher comorbidity scores than those in the MA group. In the univariate analysis, the hazard ratio (HR) of serious GVHD for the NMA group compared to the MA group was 1.71 (95% C.I., 1.1–2.6) (p = 0.01). After adjusting for patient age, patient and donor gender, donor type, HLA-mismatch, aggressive versus indolent malignancy at HCT, remission versus relapse at HCT, myeloid versus non–myeloid malignancy, HCT co–morbidity index, and prior donor lymphocyte infusion, the HR of serious GVHD was 1.50 (95% C.I., 0.8–2.7) (p = 0.17). After censoring for recurrent or progressive malignancy after HCT, the cumulative incidence of serious GVHD at 3 years was 21% for the NMA group and 14% for the MA group, and the HR was 1.33 (95% C.I., 0.7–2.6) (p = 0.40). Reasons for categorization of GVHD as serious (i.e., death, lengthy hospitalization, major disability, or recurrent major infections) were similar between the MA and NMA cohorts. Among the 44 patients with serious GVHD in the MA group, 19 (43%) had serious acute GVHD, and 25 (57%) had serious chronic GVHD. Among the 43 patients with serious GVHD in the NMA group, 20 (46%) had serious acute GVHD, and 30 (70%) had serious chronic GVHD. Among the 264 MA patients, 28 (11%) had grade III–IV acute GVHD and 147 (56%) had extensive chronic GVHD that did not meet the criteria for serious GVHD, compared to 7 (4%) and 84 (49%) of the 171 NMA patients, respectively. We conclude that the type of pretransplant conditioning regimen does not have a large effect on the incidence of serious GVHD after HCT. Assessment of serious GVHD provides additional useful information to acute GVHD grades and the classification of limited and extensive chronic GVHD in describing overall GVHD-related outcomes after HCT. MA NMA Outcome, n (%) n = 264 n = 171 Serious GVHD 44 (17) 43 (25) Grades III–IV acute GVHD 54 (20) 27 (16) Extensive chronic GVHD 174 (66) 114 (68) 2-year nonrelapse mortality 66 (25) 43 (25)

scholarly journals Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation

Blood ◽  
2016 ◽  
Vol 127 (11) ◽  
pp. 1502-1508 ◽  
Author(s):  
Marco Mielcarek ◽  
Terry Furlong ◽  
Paul V. O’Donnell ◽  
Barry E. Storer ◽  
Jeannine S. McCune ◽  
...  
Keyword(s):  
Blood Cell ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Host Disease ◽  
Graft Versus Host ◽  
Key Points ◽  
Conventional Immunosuppression ◽  
Low Incidence

Key Points With conventional immunosuppression, the incidence of chronic GVHD is higher after transplantation of mobilized blood compared with marrow. Administration of cyclophosphamide after mobilized blood cell transplantation is associated with a low incidence of chronic GVHD.

Prognostic Relevance of “Early-Onset” Graft-Versus-Host Disease Following Nonmyeloablative Hematopoietic Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 423-423
Author(s):  
Marco Mielcarek ◽  
Lauri Burroughs ◽  
Wendy Leisenring ◽  
Paul Martin ◽  
Razvan Diaconezcu ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Early Onset ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Unrelated Donors

Abstract We have shown that graft-versus-host disease (GVHD) after nonmyeloablative hematopoietic cell transplantation (HCT) occurs a median of 2 months later than after myeloablative HCT (Blood 102:756, 2003). Here, we asked whether there was an association between the time of onset of GVHD and survival after nonablative HCT. We retrospectively analyzed outcomes among 395 patients with hematologic diseases who had nonmyeloablative HCT from HLA-matched related (n=297) or unrelated donors (n=98). The nonablative regimen consisted of 2 Gy total body irradiation with or without fludarabine followed by postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. The cumulative incidences of grades II-IV acute GVHD and extensive chronic GVHD were 45% and 47%, respectively, with grafts from related donors, and 68% and 68%, respectively, with those from unrelated donors. The median time to prednisone initiation, a marker for the onset of both acute and chronic GVHD, was 79 (range, 8–799) days among patients with sibling donors and 28 (range, 5–104) days among patients with unrelated donors. Among patients with GVHD following related grafts (n=187), the cumulative incidence of non-relapse mortality (NRM) at 4 years was 55% among the tertile of patients who initiated prednisone before day 50 (“early initiation”), and 29% when prednisone was initiated on or after day 50 (“late initiation”; p&lt;0.001). After controlling for patient age, diagnosis, type of preparative regimen, number of previous chemotherapies and donor/recipient gender combinations in multivariate analysis, early initiation of prednisone was identified as an independent predictor of increased NRM (Table). The presence of comorbidid conditions at the time of transplant (Charlson Comorbidity Index &gt;=1) was neither predictive for the time of onset nor the overall incidence of GVHD. Among patients who initiated prednisone for the treatment of GVHD, those with pretransplant comorbidities had a significantly greater hazard of NRM than those without comorbidities (hazard ratio, 2.6; 95% confidence interval, 1.2–5.4; p=0.01). There was no association between time to prednisone initiation and survival after nonmyeloablative HCT from unrelated donors. In conclusion, early-onset GVHD (prednisone initiation before day 50) was associated with increased NRM and poor survival after nonmyeloablative HCT from HLA-identical related donors and identified a subgroup of patients who might benefit from more aggressive primary therapy of GVHD. Hazard of Non-Relapse Mortality According to Time to Prednisone Initiation (HLA-Matched Related Transplants) Prednisone Initiation for Treatment of GVHD [Day] Hazard Ratio† 95% Confidence Interval P* P** †Cox proportional hazards model treating “early vs. late prednisone initiation” as a time-dependent covariate; *compared to “not initiated”; **comparison of prednisone initiation &lt;day 50 vs.≥day 50 Not initiated 1.0 --- --- --- &lt;50 11.4 5.3–24.4 &lt;0.001 --- ≥50 6.3 2.8–14.5 &lt;0.001 0.04

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