Repeated CD45RA‐depleted DLI successfully increases donor chimerism in a patient with beta‐thalassemia major after haploidentical stem cell transplant

2020 ◽  
Author(s):  
Wilson Y. K. Chan ◽  
Janette S. Y. Kwok ◽  
Alan K. S. Chiang ◽  
Godfrey C. F. Chan ◽  
Pamela P. W. Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Cell Transplant ◽  
Donor Chimerism ◽  
Beta Thalassemia Major

Posterior Reversible Encephalopathy Syndrome in Beta Thalassemia Major Transplants: A Single Center Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5458-5458
Author(s):  
Amrith Mathew ◽  
Chepsy C Philip ◽  
M Joseph John
Keyword(s):  
Stem Cell ◽  
Calcineurin Inhibitors ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Mri Findings ◽  
Beta Thalassemia Major ◽  
Stem Cell Product ◽  
History Of ◽  
Mri Changes ◽  
Reversible Encephalopathy

Abstract Background: Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome characterized by clinical finding of hypertension, seizures, behavioral changes and altered vision, coupled with MRI abnormalities, known to occur after hematopoietic stem cell transplantation, potentially associated with calcineurin inhibitors. There is limited literature on the clinical and radiological findings in patients with PRES undergoing transplant for beta thalassemia major. Method: A Retrospective analysis of the incidence and characteristics of PRES was performed on transplants done between November 2008 and May 2015. This study assessed the frequency, etiology, clinical and imaging characteristics in patients undergoing stem cell transplantation for beta thalassemia major. Results: A total of 88 bone marrow transplants (BMT) were performed for various indications and among them 39 transplants were for patients with thalassemia major. The median age among the beta thalassemia group was 9 years (range 2-18). Two different regimens were used for thalassemia. Table: 1 Cyclosporine A (CSA) and short course methotrexate were used as graft versus host disease (GVHD) prophylaxis in all allogeneic transplants. A total of 6 (6.7%) patients developed PRES. Two (4%) were among non-thalassemia transplants and 4 (10%) were among thalassemia transplants. (p= 0.276). Among the beta thalassemia transplants, 2 (7%) of them underwent matched related donor (MRD) and 2 (22%) had matched unrelated donor (MUD) transplants. All patients who developed PRES belonged to either Pesaro class II or III risk group. Table 1. High blood pressure recordings above 95th centile were noted in all the patients prior to the onset of seizure and all of them (100%) complained about persisting head ache. Two patients (50%) had visual hallucinations and one of them had transient loss of vision with no ophthalmic findings. MRI changes were seen among 3 patients (75%). Of the patients who had radiological findings, T2 hyper-intensive white matter changes were present in frontal 1 (25%), parietal 3 (75%), occipital 3 (75%), and thalamus 1 (25%). Abnormalities were bilateral all in all patients who had MRI findings, but not necessarily symmetrical. None of the patients had hemorrhage or grey matter changes. The etiological factor for 3 (75%) patients was calcineurin inhibitor (CNI), CSA and the symptoms reverted on discontinuation of CSA. An increased level of CSA was noted only in on patient with a level of 358µg/L (range 131 - 358µg/L). One patient had the seizure with MRI changes following stem cell product infusion. The occurrence of PRES was not associated with previous history of seizures in any of the patients. Time to PRES ranged between 53 to 60 days in patients on calcineurin inhibitors. All patients made a complete recovery within 24-48 hours and were continued on antiepileptics. However, one patient died after status-epilepticus and brain stem injury while on tapering doses of leviteracetam at 6 months post-transplant. Conclusion: It is important to promptly recognize this syndrome based on the post-transplant day, clinical history of head ache, hypertension, visual abnormalities and MRI findings. Early imaging, withdrawal of calcineurin inhibitors, tight blood pressure control and initiation of anticonvulsants in high risk thalassemia transplants may be helpful reducing the incidence. By analyzing larger databases it may be helpful to develop diagnostic criteria and scoring for early diagnosis and intervention. Table 1. Transplant indications, types and risk stratification and conditioning regimens. Variable n (%) Total transplants 88 (100) Non Thalassemia 49 (56) Thalassaemia Class I Class II Class III MRD MUD 39 (44) 3 (8) 9(23) 27 (69) 30 (77) 9 (23) Conditioning regimen for thalassemia N = 39 Thiotepa, Treosulfan and Fludarabine 36 (92) Busulphan, Cyclophosphamide, ATG 3 (8) PRES N=6 Non-Thalassemia Thalassemia 2 (6.7%) 4 (10%) p=0.276 Etiology among thalassemia transplantsCNI Stem cell product infusion N=4 3 (75%) 1 (25%) Disclosures No relevant conflicts of interest to declare.

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.

Sign in / Sign up

Export Citation Format

Share Document