scholarly journals Sirolimus Combined with Cyclosporine (CSP) and Mycophenolate Mofetil (MMF) As Graft-Vs-Host Disease (GVHD) Prophylaxis after Nonmyeloablative (NMA) Hematopoietic Cell Transplantation (HCT) Using HLA Class I or Class II Antigen Mismatched Donors: Results from a Phase II Multi-Center Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 369-369
Author(s):  
Brian Kornblit ◽  
Barry Storer ◽  
Michael B. Maris ◽  
Niels Smedegaard Andersen ◽  
Thomas R. Chauncey ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hla Class I ◽  
Class Ii ◽  
Hematopoietic Cell ◽  
Class I ◽  
Current Trial ◽  
Gvhd Prophylaxis ◽  
Class Ii Antigen

The success of HCT is highly dependent on the availability of compatible donors. Depending on ethnicity, fully HLA-matched donors cannot be identified for 25-84% of patients. In an effort to extend the use of HLA-mismatched donors to patients only eligible for NMA HCT, we previously demonstrated that engraftment and long-term survival can be achieved using CSP and MMF immunosuppression after HLA class I antigen-mismatched HCT (Nakamae et al, 2010). Based on this trial, we designed a phase II multi-center trial to assess the efficacy of GVHD prophylaxis with triple immune suppression with CSP, MMF and sirolimus after HLA class I or class II antigen mismatched NMA HCT (fludarabine 90mg/m2 and 2-3 Gy TBI). Patients ineligible for high-dose conditioning with only HLA class I or class II antigen mismatched donors available were eligible for inclusion. The primary objective was to determine whether the incidence of grades 2-4 acute GVHD can be reduced to less than the historical rate of 70% with the triple-immunosuppression. The evaluation was planned to be carried out separately among HLA class I and class II mismatched patients. Secondary objectives included day 100 non-relapse mortality (NRM) and grades 3-4 acute GVHD. CSP was started on day -3 and continued to day +150 and then tapered off by day +180. Sirolimus was started on day -3 through day +180 and then tapered off by day +365. MMF was given thrice daily from days 0 to +30 then twice daily to day +100 and tapered off by day +150. A total of 76 patients were enrolled and received conditioning with fludarabine and TBI followed by infusion of unmodified G-CSF mobilized peripheral blood stem cell (PBSC) grafts. The median age was 63 (21-76) years, and median follow-up of surviving patients was 47 (4-94) months. 51 (67%) and 25 (33%) of patients had HLA class I or II mismatches, respectively. Transplant demographics are summarized in Table 1. Sustained engraftment was observed in all but 1 (1%) patient with myeloproliferative disease who had autologous recovery after transplant. Median number of days with neutrophils < 500 cells/ml and platelets <20,000 platelets/ml were 14 (0-67) and 2 (0-70), respectively. Full donor T-cell chimerism (>95% donor) was achieved in 48% and 63% at days +28 and 84, respectively. Outcomes are summarized in Table 2.The cumulative incidence of grade 2-4 acute GVHD at day +100 was 34% in all patients (29% and 48% after HLA class I and class II mismatched, respectively; p=0.09) (Figure 1), with only 3% of patients experiencing grade 3 acute GVHD and no patients experienced grade 4 acute GVHD. NRM at day +100, 2 years and 4 years were 4%, 15% and 17%, respectively (HLA class I vs class II: p=0.58) (Figure 2). The 2- and 4-year cumulative incidences of chronic GVHD were 54% and 57% (HLA class I vs. class II: p=0.11). Relapse incidences at 2 and 4 years were 26% and 31% with no differences between the class I and II mismatched patients (p=0.54) (Figure 2). The cumulative incidences at 2 and 4 years of progression-free survival (PFS) were 59% and 52%, and overall survival (OS) were 68% and 62% with no differences between HLA class I and II mismatches for PFS or OS (p=0.64 and 0.90, respectively) (Figure 2). Compared to historical data from our previous trial using MMF and CSP prophylaxis alone in patients with HLA class I mismatches, the addition of sirolimus to GVHD prophylaxis with CSP/MMF improved outcomes both after HLA class I or class II mismatched HCT (Nakamae et al, 2010). In a comparison of HLA class I mismatches only, day +100 grade 2-4 acute GVHD was reduced from 69% in the historical cohort to 29% in the current trial. The relapse incidences were comparable, while 2-year NRM decreased from 47%, in historical controls, to 16%, and translated into improved OS from 26% to 67% at 2 years in the current study. No difference was observed in the incidence of chronic GVHD. Furthermore, in the current trial, similar results were seen using HLA class II mismatched donors, suggesting that the triple drug immunosuppression could be used with either type of mismatch. The current trial demonstrates that triple drug immunosuppression with CSP, MMF, and sirolimus is safe and effective in reducing both acute GVHD and NRM after NMA HCT with either HLA class I or class II antigen mismatched donors. Disclosures Maloney: Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options . OffLabel Disclosure: In the current study cyclosporine, mycophenolate mofetil and sirolimus are used to prevent graft versus host disease after allogeneic hematopoietic cell transplantation. Fludarabine is used together with total body irradiation as at part of the conditioning prior to allogeneic hematopoietic cell transplantation.

scholarly journals Causes and Effects of Methotrexate Dose Alterations in Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2460-2460 ◽  
Author(s):  
Radha Ramanan ◽  
Andrew Boon Ming Lim ◽  
Kate Mason ◽  
Jeffrey Szer ◽  
David Ritchie
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
World Health ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Grade 3

Abstract Aim To identify the causes and consequences of omission and/or reduction of methotrexate (MTX) doses in graft-versus-host disease (GVHD) prophylaxis used during allogeneic hematopoietic cell transplantation (alloHCT). Method We conducted a retrospective medical record review of 125 alloHCTs performed between the years 2011 and 2013 at our hospital where MTX (15, 10, 10, 10 mg/m2 intravenously on day [D] +1, D+3, D+6, D+11 respectively) is used with cyclosporine as GVHD prophylaxis. The association of MTX dose omission with overall survival (OS), non-relapse mortality (NRM) and acute GVHD, measured from a landmark of D+12, was evaluated with univariate and multivariate analysis. Results 116 patients (median age 48, range 17-67, 59% male) were eligible for analysis. Commonest indications for alloHCT were acute leukemia (47%) and chronic lymphoproliferative disorders (28%). Conditioning was myeloablative in 54%, donors were siblings in 53%, and grafts were peripheral blood in 87%. 85 patients (73%) received all four full doses of MTX. 22 patients had a dose omission at D+11, and two at both D+6 and D+11. 43 patients were given folinic acid rescue. Documented reasons for MTX alteration were mucositis (n = 22; World Health Organisation mucositis grade 4 in 16 patients, grade 3 in 4 patients and grade 2 in 2 patients), fluid overload (n = 10), liver impairment (n = 8, median bilirubin 83 micromol/L, range 19-204 micromol/L, normal < 21 micromol/L), renal impairment (n = 8, median creatinine 138 micromol/L, range 67-276 micromol/L, normal 45-90 micromol/L) and sepsis (1). MTX omission was associated with poorer OS (48% vs 90%; hazard ratio [HR] for mortality 5.4, 95% CI 2.5-11.7, P < 0.001, Figure 1) and higher NRM (39% vs 5%, HR 10.2, 95% CI 3.4-30.8, P < 0.001, Figure 2) at 12 months post landmark. A pattern of ongoing NRM was observed beyond day 100. Strikingly, those patients who received all four full doses of MTX had NRM of 0% at 100 days post landmark. There was no difference in rates of grade 2-4 (24% vs 22%, P = .950) or grade 3-4 (9% vs 11%, P = .662) acute GVHD, or relapse (20% vs 17%, P = .514), at day 100 post landmark. Conclusion MTX dose reduction has no significant impact on GVHD development, suggesting that MTX omissions or other adjustments of GVHD prophylaxis did not lead to enhanced T cell activation. However, it seems that the need to reduce MTX indicates an increased risk of NRM, likely reflecting ongoing organ dysfunction. Older patients or those with pre-transplant co-morbidities may be better served by strategies that lower the likelihood of organ toxicity, including reduced intensity conditioning and lower initial doses of MTX. Figure 1. Overall survival according to whether or not any methotrexate (MTX) was omitted. Figure 1. Overall survival according to whether or not any methotrexate (MTX) was omitted. Figure 2. Non-relapse mortality according to whether or not any methotrexate (MTX) was omitted. Figure 2. Non-relapse mortality according to whether or not any methotrexate (MTX) was omitted. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Relevance of HLA Supertype Matching after Myeloablative Conditioning 7/8 Unrelated Donor Hematopoietic Cell Transplantation: A CIBMTR Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2572-2572
Author(s):  
Aleksandr Lazaryan ◽  
Tao Wang ◽  
Stephen R. Spellman ◽  
Hai-Lin Wang ◽  
Carlheinz R. Müller ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hla Class I ◽  
Hematopoietic Cell ◽  
Class I ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Increased Risk ◽  
The Impact

Abstract The diversity of the HLA class I and II alleles can be simplified by consolidating them into fewer supertype clusters based on functional or predicted structural similarities in epitope binding grooves of HLA molecules. HLA class I and II supertypes have been increasingly studied in association with immune susceptibility to infection and cancer with potential implications for vaccine development. However, the significance of individual allele mismatching within and outside of HLA class I or II supertypes remains unknown in the context of hematopoietic cell transplantation (HCT). We therefore studied the impact of HLA supertype disparities on clinical outcomes of 1934 patients with AML (45%), ALL (31%), CML (14%) or MDS (9%) who underwent 7/8 unrelated donor myeloablative conditioning HCT from 1999 to 2011 and were registered with CIBMTR. Median age at transplant was 35 years (range, 1-70); 53% were males; 81% Caucasian; 56% received peripheral blood grafts; 50% were ABO-mismatched; 36% had in-vivo T-cell depletion; 62% received tacrolimus- and 36% cyclosporine A-based GVHD prophylaxis; 72% male or non-parous female donors; median follow up of survivors was 54 months (3-149). Supertype assignment methods of (1) revised main HLA anchor specificities (Sydney, 2008) and (2) bioinformatics (Doytchinova, 2004-05) were used to categorize single mismatched alleles into 6 HLA-A (A01, A01A03, A01A24, A02, A03, A24), 6 HLA-B (B07, B08, B27, B44, B58, B62), 2 HLA-C (C1, C2), and 5 DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Overall survival (OS), disease-free survival (DFS), relapse, treatment-related mortality (TRM), acute graft vs. host disease (aGVHD) and chronic GVHD were compared across matched vs. mismatched HLA-A (265 vs. 429), -B (230 vs. 92), -C (365 vs. 349), and -DRB1 (153 vs. 51) supertypes. We used predetermined α=0.01 for statistical significance as multiple exploratory analyses were conducted by Kaplan-Meier, Gray, and Cox proportional hazard methods. In the multivariable analysis, supertype B-mismatch was associated with increased risk of grade II-IV aGVHD (HR=1.78; 95% CI, 1.23-2.59, p=0.0025), however no difference was found for grade III-IV aGVHD or other clinical outcomes compared to supertype B-matches. Supertype DRB1-mismatch was associated with shorter neutrophil recovery (HR=0.51; 95% CI, 0.36-0.71, p=0.0001), yet a trend toward inferior OS (HR=1.58; 95% CI 1.04-2.38, p=0.037) and higher TRM (HR=1.64; 95% CI, 0.99-2.74, p=0.0565) compared to DRB1 matches within supertypes. There was no increased risk of GVHD with DRB1 supertype mismatch. No associations were observed between HLA-A and -C supertypes or aggregate supertype-matched vs. -mismatched groups for any outcomes. Our analysis demonstrated differential influence of HLA supertype-based allele matching within -B and -DRB1 loci on clinical outcomes after myeloablative 7/8 URD HCT. Disclosures No relevant conflicts of interest to declare.

Gvhd Prophylaxis With Mycophenolate Mofetil and Calcineurin Inhibitor In Allogeneic Hematopoietic Cell Transplantation From HLA-Matched Siblings Or 7–8/8 HLA-Matched Unrelated Volunteer Donors: A Japanese, Multicenter, Phase II Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4586-4586
Author(s):  
Takahiko Nakane ◽  
Hirohisa Nakamae ◽  
Saiko Kurosawa ◽  
Atsuo Okamura ◽  
Michihiro Hidaka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mycophenolate Mofetil ◽  
Cell Transplantation ◽  
Primary Endpoint ◽  
Calcineurin Inhibitor ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Gvhd Prophylaxis ◽  
Neutrophil Engraftment

Background In allogeneic hematopoietic cell transplantation (allo-HCT), graft versus host disease (GVHD) remains a major cause of non-relapse mortality. Although methotrexate (MTX) combined with a calcineurin inhibitor (CI) is the current standard for GVHD prophylaxis, several recent studies have also reported the utility of mycophenolate mofetil (MMF) combined with CI, in terms of earlier hematological recovery and less mucositis with a similar incidence of GVHD. In Asian populations, however, there have been few prospective studies with MMF and CI as GVHD prophylaxis, and we thus carried out this Japanese multicenter prospective trial of allo-HCT with MMF and CI. Methods From April 2010 to September 2012, we prospectively registered patients with hematological malignancy who received their first T cell-replete allo-HCT from HLA-matched related donors (MRD group) or 8/8 or 7/8 matched unrelated volunteer donors (URD group). The primary endpoint was the cumulative incidence of grade II to IV acute GVHD at day 100. The expected and threshold incidences were 30% and 60% in MRD group, and 40% and 65% in URD group, respectively. With a statistical power of 80% and a one-sided, type I error of 5%, the each number of eligible patients required for these studies was calculated to be 17 and 25 in MRD and URD groups, respectively, and the each maximal number of registerable patients was set to be 30 and 45, respectively. As of June 2013, the primary endpoint for evaluation of all patients has been attained. As GVHD prophylaxis, MMF (500mg three times/day) and cyclosporine were used in MRD group, and MMF (1000mg three times/day) and tacrolimus were used in URD group. The MMF dose was tapered according to plan, starting on day 30–40 with cessation by day 100. The cyclosporine and tacrolimus were continued until days 60 and 100 and then tapered and stopped on days 150 and 180, respectively, unless GVHD developed. Results There were 20 patients (median age:47.5) in the MRD group and 31 patients (median age:45) in the URD group (HLA 8/8 matches:23, HLA 7/8 matches:8). In the MRD and URD groups, acute leukemia was present in 90% and 65%, and standard risk disease comprised 90% and 65%, respectively. In the MRD and URD groups, 75% (15/20) and 55% (17/31) received standard myeloablative conditioning (BuCy or CyTBI), and the remainder received reduced intensity conditioning (FluBu±TBI or FluMel±TBI). In the MRD group, peripheral blood stem cells and bone marrow were used in seven and 13 patients, respectively. In the URD group, all 31 patients received allo-HCT from a bone marrow donor. The cumulative incidences of grades II to IV and III to IV acute GVHD on day 100 were 45% (90% confidence interval [CI]:26.9-63.1) and 15% in the MRD group, respectively. The primary endpoint was not achieved in the MRD group, although the dose of MMF in the MRD group (1.5g/day) was lower than the URD group (3g/day). In contrast, the cumulative incidences of grades II to IV and III to IV acute GVHD on day 100 were 19.4% (90%CI:8.0-30.8) and 6.5% in the URD group, respectively. The primary endpoint was achieved in the setting of allo-HCT form URD. In the MRD and URD groups, cumulative incidences of neutrophil engraftment were 94.7% and 96.8%, and the median times to neutrophil engraftment were 12 days (range:10–13) and 13 days (range:8–26), respectively. Although one patient in the MRD group and 3 patients in the URD group experienced secondary graft failure, all of them recovered with dose adjustment of myelosuppressive drugs including MMF. Grade 3 stomatitis occurred only in 10% of the MRD group and 13% of the URD group, and there was no grade 4 stomatitis in either group. The cumulative incidences of late onset acute GVHD and chronic GVHD at one year were 12.5% and 37.5% in the MRD group, and 7.4% and 29.6% in URD group, respectively. With a median follow-up of 589 days in surviving patients, 1-year overall survival was 89.1% in the MRD group and 86.0% in the URD group. The 1-year cumulative incidences of non-relapse mortality and relapse were 10.9% and 11.9% in the MRD group, and 6.5% and 31.6% in URD group, respectively. Conclusion Our study confirmed that GVHD prophylaxis with MMF plus CI was associated with earlier hematological recovery and less mucositis. The use of MMF (3g/day) plus tacrolimus was a feasible and effective option as GVHD prevention in allo-HCT from 7/8 or 8/8 HLA-matched URD. Further studies will be needed to clarify the optimal dose of MMF in allo-HCT from MRD. Disclosures: Nakane: Chugai Pharma: Travel/accommodations/meeting expenses Other. Off Label Use: CellCept (mycophenolate mofetil). This drug was a primary drug to be evaluated for GVHD prophylaxis in this study. Nakamae:Chugai Pharma: Travel/accommodations/meeting expenses Other. Hino:Chugai Pharma: Honoraria, Research Funding, Travel/accommodations/meeting expenses Other.

scholarly journals Sirolimus with CSP and MMF as GVHD prophylaxis for allogeneic transplantation with HLA antigen–mismatched donors

Blood ◽  
2020 ◽  
Vol 136 (13) ◽  
pp. 1499-1506
Author(s):  
Brian Kornblit ◽  
Barry E. Storer ◽  
Niels S. Andersen ◽  
Michael B. Maris ◽  
Thomas R. Chauncey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mycophenolate Mofetil ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hla Class I ◽  
Primary Objective ◽  
Class I ◽  
Hla Antigen ◽  
Gvhd Prophylaxis

Abstract This trial aimed to evaluate the efficacy of sirolimus in addition to cyclosporine (CSP) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after nonmyeloablative conditioning for HLA class I or II mismatched hematopoietic cell transplantation (HCT). Eligible patients had hematologic malignancies treatable by allogeneic HCT. Conditioning consisted of fludarabine (90 mg/m2) and 2 to 3 Gy total body irradiation. GVHD prophylaxis comprised cyclosporine, mycophenolate mofetil, and sirolimus. The primary objective was to determine whether the cumulative incidence of grade 2 to 4 acute GVHD could be reduced to &lt;70% in HLA class I or II mismatched HCT. The study was closed on December 20, 2018. Seventy-seven participants were recruited between April 14, 2011, and December 12, 2018, of whom 76 completed the study intervention. Median follow-up was 47 months (range, 4-94 months). The cumulative incidence of grade 2 to 4 acute GVHD at day 100 was 36% (95% confidence interval [CI], 25-46), meeting the primary end point. The cumulative incidence of nonrelapse morality, relapse/progression, and overall survival was 18% (95% CI, 9-27), 30% (interquartile range, 19-40), and 62% (95% CI, 50-73) after 4 years. In conclusion, the addition of sirolimus to cyclosporine and mycophenolate mofetil resulted in a lower incidence of acute GVHD, thus translating into superior overall survival compared with historical results. This trial was registered at www.clinicaltrials.gov as #NCT01251575.

A Prospective Study of Donor ImmuKnow® as a Biomarker for Acute GvHD in Hematopoietic Cell Transplantation Recipients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4646-4646
Author(s):  
Yubin Kang ◽  
Angelica DeOliveira ◽  
Linda Peel ◽  
Dong-Feng Chen ◽  
Nelson J. Chao
Keyword(s):  
Stem Cell ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Post Transplant ◽  
Cell Counts ◽  
Gvhd Prophylaxis ◽  
Grade Ii

Abstract Abstract 4646 Introduction Graft versus host disease (GvHD) occurs in ∼40% of allogeneic hematopoietic cell transplantation (HCT) recipients and is associated with substantial morbidity and mortality. The exact mechanisms underlying GvHD remain to be defined, but donor immune cells are thought to play a major role in the pathogenesis of GvHD. Depletion of donor lymphocytes reduces the risk of GvHD but to the expense of disease relapse and lower engraftment. Immunological parameters of donor cells that predispose a recipient to GvHD will be of great value. The Cylex” ImmuKnow® assay determines the strength of immune function by quantifying the amount of ATP released from phytohemagglutinin-stimulated peripheral blood CD4+ cells. The amount of ATP production is a measure of lymphocyte activity. In our current study, we utilized the ImmuKnow® to assess whether a donor's immune response correlates with early outcomes in recipients post-HCT. Patients and Methods Twenty-six (26) donor-recipient pairs were included in our study (15 HLA identical sibling HCT and 11 haploidentical HCT). The median age of recipients at the time of transplantation was 49 years (range, 23-65). Twelve were female and 14 male. The median age of donors was 45 years (range, 18-67), and half of them were female. Recipients received an average cell-dose of 10.7 ± 4.9 × 106 CD34+ cells/kg. Twenty-one patients received nonmyeloablative, reduced intensity conditioning consisting of Fluarabine, Busulfan or melphlan, and alemtuzumab, and mycophenolate mofetil was given for GvHD prophylaxis in these recipients. Five patients received myeloablative conditioning with total body irradiation or Busulfan, and cyclophosphamide. Methotrexate with/without cyclosporine or tacrolimus alone was used for GvHD prophylaxis in myeloablative patients. Stem cell source was G-CSF-mobilized peripheral blood. Blood samples obtained prior to G-CSF mobilization and prior to stem cell collection (approximately 2 weeks apart) were assayed for ImmuKnow values and cell counts (WBC, ANC, ALC & CD34+ count). Results G-CSF mobilization led to a significant increase in ImmuKnow® ATP values from 342 to 728 ng/mL (p<0.001) along with an increase in all measured cell counts. Average ImmuKnow® values from recipients were 108 ± 116 at 2-3 weeks post-transplant, 231± 221 at 4-5 weeks, and 104 ± 95 ng/mL at 8-10 weeks. Grade ≥ II acute GvHD occurred in 27% of haploidentical HCT recipients (3/11 patients) and 20% of HLA identical HCT recipients (3/15 patients). We found no correlations between recipient post-transplant ImmuKnow® values and GvHD. No correlations were observed between various donor cell counts (WBC, ANC, ALC or CD34+ cell dose) and GvHD. In haploidentical HCT, mobilized donor blood ImmuKnow® ATP values did not correlate with GvHD. However, donor ImmuKnow® values correlated with increased risk of acute GvHD in HLA identical sibling HCT. ROC analysis of mobilized donor samples showed that in HLA identical sibling HCT ATP values in excess of 747 ng/mL predicted grade II or higher GvHD with a likelihood ratio of 4.00 (2.9-5.5, 95% confidence), sensitivity of 100%, and specificity of 75% (AUC=0.889, p=0.003) . Conclusions In HLA identical matched sibling transplantation, very strong ATP values (>747 ng/mL) following mobilization correlated with the risks of developing grade II or higher GvHD during the first 90 days post-transplant. If confirmed in larger studies, these data suggest that ImmuKnow can serve as an independent predictor/biomarker for the development of GvHD in HLA identical HCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Poor Outcomes of HLA-Mismatched Allogeneic Hematopoietic Cell Transplantation and High Ferritin Levels after a Reduced-Intensity Conditioning Regimen in Patients with Advanced Myelofibrosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5742-5742
Author(s):  
Han Bi Lee ◽  
Jae-Ho Yoon ◽  
Gi June Min ◽  
Sung-Soo Park ◽  
Silvia Park ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Advisory Committees ◽  
Reduced Intensity

Allogeneic hematopoietic cell transplantation (allo-HCT) preconditioning intensity, donor choice, and graft-versus-host disease (GVHD) prophylaxis for advanced myelofibrosis (MF) have not been fully elucidated. Thirty-five patients with advanced MF were treated with reduced-intensity conditioning (RIC) allo-HCT. We searched for matched sibling (n=16) followed by matched (n=10) or mismatched (n=5) unrelated and familial mismatched donors (n=4). Preconditioning regimen consisted of fludarabine (total 150 mg/m2) and busulfan (total 6.4 mg/kg) with total body irradiation≤ 400cGy. All showed engraftments, but four (11.4%) showed either leukemic relapse (n=3) or delayed graft failure (n=1). Two-year overall survival (OS) and non-relapse mortality (NRM) was 60.0% and 29.9%, respectively. Acute GVHD was observed in 19 patients, and grade III-IV acute GVHD was higher with HLA-mismatch (70% vs. 20%, p=0.008). Significant hepatic GVHD was observed in nine patients (5 acute, 4 chronic), and six of them died. Multivariate analysis revealed inferior OS with HLA-mismatch (HR=6.40, 95%CI 1.6-25.7, p=0.009) and in patients with high ferritin level at post-HCT D+21 (HR=7.22, 95%CI 1.9-27.5, p=0.004), which were related to hepatic GVHD and high NRM. RIC allo-HCT can be a valid choice for advanced MF. However, HLA-mismatch and high post-HCT ferritin levels related to significant hepatic GVHD should be regarded as poor-risk parameters. Disclosures Kim: Handok: Honoraria; Amgen: Honoraria; Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL & H: Research Funding; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lee:Alexion: Consultancy, Honoraria, Research Funding; Achillion: Research Funding.

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