scholarly journals The impact of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on transplant-related variables after allogeneic hematopoietic cell transplantation in patients receiving MTX as GVHD prophylaxis

2008 ◽  
Vol 42 (6) ◽  
pp. 429-430 ◽  
Author(s):  
E Soydan ◽  
P Topcuoglu ◽  
K Dalva ◽  
M Arat
Keyword(s):  
Gene Polymorphism ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Gvhd Prophylaxis ◽  
The Impact

Validation of Favourable Impact of Large Granular Lymphocytosis after Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3936-3936
Author(s):  
Marc Poch Martell ◽  
Jieun Uhm ◽  
Naheed Alam ◽  
Vikas Gupta ◽  
Jeffrey H. Lipton ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Predictive Factors ◽  
Lymphocyte Count ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Gvhd Prophylaxis ◽  
Significant Difference ◽  
Persistent Elevation

Abstract Introduction: We previously reported on the incidence of large granular lymphocytosis (LGL) following allogeneic hematopoietic cell transplantation (allo-HCT), its favorable impact on outcome and the predictive factors associated with its development (D Kim, BMT, 2013). In the current study we aimed to validate our previous findings in an independent set of patients. Methods:All 408 patients undergoing allo-HCT at Princess Margaret Cancer Centre, Toronto, from 2007 to 2012 (replication set) were included retrospectively. Data from the previously reported set of patients undergoing allo-HCT from 2000 to 2007 (n = 418) (original set) were updated. Results:There were significant differences between original and replication sets in baseline characteristics (age, underlying disease, conditioning, GvHD prophylaxis, graft source, donor type, and incidences of GvHD and CMV viremia) in accordance to the changes over a decade in allo-HCT procedures. The cumulative incidence of LGL lymphocytosis at 3 years was 21.8% in the original set and 11.7% in the replication set (P<0.001). The median onset of LGL lymphocytosis was 362 days after HCT in the original set and 223 days in the replication set. Patients with LGL lymphocytosis showed a persistent elevation of lymphocyte count compared to patients without LGL lymphocytosis (P<0.001). Patients with LGL lymphocytosis showed a higher overall survival (OS) (86.4% vs 46.1%, P<0.001, Fig. A) and lower non-relapse mortality (NRM) (10.5% vs 36.3%, P<0.001, Fig. B) at 3 years. No significant difference was found in relapse incidence according to the development of LGL lymphocytosis (13.9% vs 19.6%, P=0.25). Multivariable analysis confirmed the favorable impact of LGL lymphocytosis on OS (HR 0.30, P=0.02) and a trend towards lower NRM (HR 0.27, P<0.001, original set; HR 0.50, P=0.22, replication set). No effect of LGL lymphocytosis on relapse incidence was demonstrated (HR 1.24, P=0.37, original set; HR 0.53, P=0.29, replication set). Patients with LGL lymphocytosis showed a trend towards a higher incidence of IST cessation after cGvHD: 63.6% at 7 years vs 53.4% in patients without LGL lymphocytosis, P=0.07. The previously identified predictive factors for the development of LGL lymphocytosis were replicated: higher incidence of LGL lymphocytosis with 1) CMV seropositive recipients (29.6% vs 5.1%, P < 0.001); 2) CMV viremia (31.0% vs 8.9%, P<0.001) and 3) chronic GvHD (28.2%, vs 5.0%, P<0.001). Conclusions: The favorable impact of LGL lymphocytosis following allo-HCT in OS and NRM, as well as the predictive factors for the development of LGL lymphocytosis were successfully validated in an independent cohort of patients. No impact of LGL lymphocytosis on relapse incidence was noted. The difference in transplantation procedures between the two cohorts, such as GvHD prophylaxis/T-cell depletion, may explain the lower incidence of LGL lymphocytosis in the replication cohort. Patients with LGL lymphocytosis showed a trend towards a higher incidence of IST cessation after cGvHD, which may explain the lower NRM. Patients with LGL lymphocytosis showed a persistent elevation of lymphocyte count and had an indolent course. OS and NRM according to the development of LGL lymphocytosis Disclosures No relevant conflicts of interest to declare.

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 Practical Aspects of Allogeneic Hematopoietic Cell Transplantation for Patients with Poor-Risk Chronic Lymphocytic Leukemia

2011 ◽  
Vol 11 ◽  
pp. 161-172 ◽  
Author(s):  
Julio Delgado ◽  
Rafael F. Duarte
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Poor Risk ◽  
Gvhd Prophylaxis ◽  
Conditioning Regimens

Allogeneic hematopoietic cell transplantation has become a viable option for younger patients with poor-risk chronic lymphocytic leukemia. The results obtained with either conventional or reduced-intensity conditioning regimens have been recently evaluated and compared with alternative nontransplant strategies. This manuscript deals with practical aspects of the procedure, including patient and donor selection, conditioning regimen, GVHD prophylaxis, disease monitoring, infectious and noninfectious complications, and timing of the procedure. Finally, we speculate on how we could improve the results obtained with the procedure and new advances currently in clinical trials.

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