scholarly journals Clinical Profile and Outcome of Patients with Graft Rejection Following Related HLA Matched Allogeneic Stem Cell Transplant for β Thalassemia Major

2014 ◽  
Vol 20 (2) ◽  
pp. S241
Author(s):  
Vikram Mathews ◽  
Abhijeet Ganapule ◽  
Biju George ◽  
Kavitha Lakshmi ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Rejection ◽  
Stem Cell Transplant ◽  
Thalassemia Major ◽  
Clinical Profile ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant

Clinical Profile and Outcome Of Patients With Graft Rejection Following Related HLA Matched Allogeneic Stem Cell Transplant For β Thalassemia Major

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4546-4546
Author(s):  
Vikram Mathews ◽  
Abhijeet Ganapule ◽  
Biju George ◽  
Kavitha M Lakshmi ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Median Time ◽  
Graft Rejection ◽  
Graft Failure ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant

Allogeneic stem cell transplant (SCT) remains the only curative option for patients with β thalassemia major (TM). Graft rejections post SCT are unfortunately a common problem in this condition. There is limited data on the clinical profile and long term outcome of patients who have had a graft rejection post allogeneic SCT. We undertook a retrospective analysis of patients who had a graft failure post allogeneic SCT for TM at our center. From October, 1991 to April, 2013, 400 HLA matched related transplants for TM was done at our center. The median age was 8 years (range: 1-24) and there were 250 (62.5%) males. 154 (38.5%) were Lucarelli Class II and 229 (57.2%) were in the Class III risk group. Majority (72%) received a busulfan based conditioning regimen while 22% received a treosulfan based regimen. Bone marrow was the source of stem cells in 81% and PBSC in the rest. Majority of the patients received a CSA plus short course methotrexate GVHD prophylaxis regimen. There were 48 (12%) graft rejections in this cohort. Among these 26 (54%) were primary graft failures (PGF) while 22 (46%) were secondary graft failures (SGF). The median time to a secondary graft failure was 122 days (range: 40 - 2210). Of the 26 PGF, 9(34.6%) had autologous recovery with recurrence of transfusion dependence while 17(65.4%) had pancytopenia. 11 (42.3%) of PGF died prior to second transplant, 10 had a second transplant and 3(11.53%) had recurrence of TM but were alive and well. Among the 22 SGF, 10(45.5%) had autologous recovery. Of the SGF, 2 died prior to a second transplant while 9 had a second transplant and the remaining (n=11) had recurrence of TM and were on conservative management. Among the 29 cases that did not receive a second transplant 14 died at a median time of 20 days from date of documented rejection (range: 0-3268). The major cause of death in this group was graft failure with infection (n=10) and regimen related toxicity (RRT; N=4). Of the remaining cases, 14 have recurrent TM and are alive and well on conservative management while one patient is alive with pancytopenia and is transfusion dependent. 19 (39%) of the patients with graft rejection underwent a second allogeneic SCT. The median time from graft rejection to second transplant was 6 months (range: 0-42). Conditioning regimen for second SCT was busulfan based in 5 (26.3%), treosulfan based in 5 (26.3%) and the remaining received non-myeloablative conditioning regimens (fludarabine based, low dose TBI, OKT3, Cy-OKT3) in view of pancytopenia. The source of stem cells was BM in 7(36.84%) and PBSC in the rest. All cases conditioned with treosulfan based regimen received a PBSC graft. The OS and EFS of the patients that had a second transplant was 41.4±12.8% and 37.6±12.2% respectively. None of the patients conditioned with a treosulfan based regimen died or had a second graft rejection (data summarized in table 1). Of the remaining 14 patients 11 died of second graft rejection while 3 (all busulfan based conditioning) are alive and well at 3, 23 and 81 months from second transplant.Table 1Clinical profile and outcome of patients with graft rejections who underwent a second allogeneic SCT with a treosulfan based conditioning regimen and PBSC graft. All patients engrafted and are alive and transfusions independent at last follow upSerial NoAge (years)SexLiver size (cms)Lucarelli ClassStem cell dose (x10E6/kg)Acute GVHDChronic GVHDLast follow up (mths)17M2310.34NILYes10.422M4213.7NILNIL3.635M4310NILNIL3.6418M2310Grade 4NIL4.9518M13315NILNIL2.9 In conclusion graft rejection following allogeneic SCT for patients with TM are associated with poor clinical outcomes. Following a second transplant there is a high incidence of deaths due second graft rejection and infections. A treosulfan based reduced toxicity myeloablative regimen with a PBSC graft has potential to significantly improve the outcome in this group of patients. Disclosures: No relevant conflicts of interest to declare.

Delay In Onset Of First Transfusion and Increased Risk Of Graft Rejection In β Thalassemia Patients Undergoing a HLA Matched Related Allogeneic Stem Cell Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 701-701
Author(s):  
Vikram Mathews ◽  
Abhijeet Ganapule ◽  
Kavitha M Lakshmi ◽  
Biju George ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Rejection ◽  
Stem Cell Transplant ◽  
Thalassemia Major ◽  
Blood Transfusions ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Liver Size ◽  
Increased Risk ◽  
The Impact

Abstract Allogeneic stem cell transplant (SCT) remains the only curative option for patients with β thalassemia major (TM). Graft rejection has been a major problem in this group of patients. The increased risk of graft rejection has often been attributed to the number of blood transfusions that these patients are exposed to. However, the published data is confusing with one large series suggesting that patients who had >100 transfusion pre-SCT had a significantly lower risk of graft rejection (Blood 1996; 87: 2082). It is also generally accepted that in patients with thalassemia intermedia the risk of alloimmunisation (red cell) is reduced if transfusion is initiated <12 months of age (Vox Sang 1990; 58:50). We undertook a retrospective analysis to study the impact of age at first transfusion on graft rejection among patients with TM who received an allogeneic SCT at our center. From October, 1991 to April, 2013, 400 HLA matched related transplants for TM was done at our center. The median age was 8 years (range: 1-24) and there were 250 (62.5%) males. 154 (38.5%) were Lucarelli Class II and 229 (57.2%) were in the Class III risk group. Majority (72%) received a busulfan based conditioning regimen while 22% received a treosulfan based regimen. Bone marrow was the source of stem cells in 81% and PBSC in the rest. Majority of the patients received a CSA plus short course methotrexate GVHD prophylaxis regimen. There were 11 (2.8%) early regimen related toxicity (RRT) deaths prior to day 12 and these were excluded for analysis of graft rejection. Of the remaining 389 cases there were 48 (12.3%) graft rejections. Among these 26 (54%) were primary graft failures while 22 (46%) were secondary graft failures. The median time to a secondary graft failure was 122 days (range: 40 - 2210). The median age at first transfusion in this cohort was 6 months (range: 1-66; data not available in 10). The median number of blood transfusions prior to SCT was 85 (range: 4 – 450). Table 1 summarizes the comparison between the group of patients who rejected there graft versus those that did not after excluding early pre-engraftment RRT deaths. After excluding early RRT deaths the EFS and OS of the entire cohort was 70±2.5% and 77±2.2% respectively. Figure 1 illustrates the age at first transfusion between the two groups. On a univariate cox regression analysis the variables that impacted graft rejection significantly were donor age (P=0.000), liver size (P=0.007) and increased age at first blood transfusion (P=0.035). The total number of transfusions prior to SCT was not significantly associated with graft rejection (P=0.894). On a multivariate analysis only liver size (P=0.019) and age at first transfusion (P=0.022) retained their statistically significant adverse effect.Table 1Baseline characteristics and comparison of patients that had a graft rejection versus those that did not after excluding early regimen related toxicity deaths (< day 12).Had graft rejection N (%) / Mean±SD/ Median(Range)Did not have graft rejection N (%) / Mean±SD/ Median(Range)Cox regressionUnivariate analysisCox regressionMultivariate analysisN48341P-valueP-valueAge (years)8 (2-19)7 (1-24)NSSex: M28 (58.3)217 (63.6)NSClass III32 (66.7)187 (54.8)NSLive size (cm)4 (1-14)3 (0-12)0.0060.019Female donor to male recipient15 (31.2)126 (37)NSSplenectomy8 (16.7)35 (10.3)0.083Age at first transfusion (months)10.5±13.47.7±6.70.0360.022Total number of transfusions prior to SCT100 (6-373)85 (4-450)NSConditioning regimen--NSBusulfan based32 (80)246 (76.2)Treosulfan based8 (20)77 (23.8)Stem cell source--NSBM44 (91.7)272 (79.8)PBSC4 (8.3)69 (20.2)CD34 cell dose9.6 (2.35-15)9 (2 – 30)NSFigure 1Figure 1. In conclusion, delay in the onset of transfusion in patients with β thalassemia major undergoing a HLA matched related allogeneic SCT probably has a greater adverse effect on engraftment than the total number of transfusions prior to SCT. Disclosures: No relevant conflicts of interest to declare.

Clinical Profile and Outcomes of Patients with β Thalassemia Major and Hepatitis C Virus Infection Undergoing an Allogeneic Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4160-4160
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Kavitha M Lakshmi ◽  
Rayaz Ahmed ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Graft Failure ◽  
Stem Cell Transplant ◽  
Thalassemia Major ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Class Iii ◽  
Liver Size

Abstract Abstract 4160 There is limited data on the prevalence, clinical profile and outcome of patients with β thalassemia major (TM) who is HCV sero-positive (HCV+) prior to an allogeneic stem cell transplant (SCT). From October, 1991 to June, 2012, 370 SCT were done for TM at our center. The median age was 7.5 years (range: 2–24) and there were 232 (62.87%) males. 209 (56.5%) belonged to Lucarelli Class III. There were 44 (11.9%) cases who were HCV+, 6 (1.6%) who were HBsAg positive and 350 (94.6%) who were CMV sero-positive at the time of pre-transplant screening. HCV+ cases were significantly older and had a significantly larger liver size. There were significantly more number of HCV+ cases who were Lucarelli Class III and the median liver enzyme and ferritin levels were higher in the HCV+ group. Table 1 summarizes these and other major differences between those who were HCV positive at diagnosis and the remaining patients. The number of graft rejections was significantly higher in the HCV+ group while the TRM was comparable between the two groups. This translated into a significantly inferior event free survival (P=0.016) though the overall survival was not significantly different (P=0.140)(Table 1). It is well recognized that patients with TM are at a high risk of developing sinusoidal obstruction syndrome (SOS) post SCT. In this series, 165 (4.6%) patients developed SOS. HCV+ cases did not have a significantly higher incidence of SOS compared to those that were HCV negative. In only 3 (6.8%) of HCV+ cases was SOS the major cause of death while SOS was a major contributory factor for death in 17 (5.2%) of the remaining cases. Among the 15 (34%) of HCV+ cases that died, the major contributory cause of death was infection (40%), graft failure (20%) and SOS (20%). On a univariate cox regression analysis, HCV+ had an adverse impact on EFS (RR=1.710; 95%CI 1.066–1.744; P=0.026). However, on a forward stepwise multivariate analysis after adjusting for conventional risk factors HCV+ status did not confer an independent adverse risk factor. Of the 29 patients who are surviving, at a median follow up of 25 months, none have had progression to chronic liver disease. 20 (69%) had a normal liver function test at last follow up while only 3 have had HCV directed therapy post transplant. From August, 2009 at our center we have been using a treosulfan based conditioning regimen for our Class III patients. Among the HCV+ cases 10 were conditioned with this regimen. This regimen was well tolerated with 100% engraftment. Two patients died, one due to sepsis and the other to GVHD. In comparison, in the historical control of HCV+ cases conditioned with a conventional busulfan based regimen where there were graft rejections in 9 (26.4%) and 13 (38.2%) deaths, the major contributory cause for death being infections (46%), SOS (23%) and graft failure (23%). In conclusion HCV+ status is a surrogate risk factor for other adverse risk factors such as older age, increased liver size and inadequate medical therapy prior to SCT. After adjusting for such risk factors HCV+ cases with TM undergoing an allogeneic SCT transplant have comparable outcomes to HCV negative cases. Use of a treosulfan based regimen is well tolerated in the HCV+ group and could potentially improve the outcome in this high risk group. Table 1: Comparison of baseline characteristics and clinicical outcomes of HCV positive and vegative cases with β thalassemia major undergoing an allogeneic stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

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