Autologous Stem Cell Rescue for Graft Failure of Second Allogeneic Stem Cell Transplant After Engraftment of Primary Allogeneic Transplant

2019 ◽  
Vol 17 (2) ◽  
pp. 281-283
Author(s):  
Atsushi Watanabe ◽  
◽  
Takeshi Inukai ◽  
Koshi Akahane ◽  
Shinpei Somazu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Failure ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Allogeneic Transplant ◽  
Stem Cell Rescue ◽  
Autologous Stem Cell Rescue

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.

Outcome of graft failure after allogeneic stem cell transplant: study of 89 patients

2014 ◽  
Vol 56 (3) ◽  
pp. 656-662 ◽  
Author(s):  
Christelle Ferrà ◽  
Jaime Sanz ◽  
Miguel-Angel Díaz-Pérez ◽  
Mireia Morgades ◽  
Jorge Gayoso ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Failure ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant

scholarly journals Real-World Outcomes in Adolescents and Young Adults with Acute Lymphoblastic Leukemia without Access to Allogeneic Stem Cell Transplant

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4373-4373
Author(s):  
Sapna Pathak ◽  
Bradley W. Christensen ◽  
Radhika Kainthla ◽  
Hsiao C. Li ◽  
Navid Sadeghi
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Lymphoblastic Leukemia ◽  
Cohort Analysis ◽  
Safety Net ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Allogeneic Transplant ◽  
Patients Âgés ◽  
Safety Net Hospital

Abstract Introduction: Adolescents and young adult (AYA) patients (ages 15-39) with acute lymphoblastic leukemia (ALL) have inferior outcomes and increased treatment-related toxicity when compared to children. The use of pediatric-inspired protocols has resulted in improved outcomes in the AYA population but outcomes remain inferior to their pediatric counterparts. Hispanic patients with ALL also have inferior outcomes compared to non-Hispanic White patients. Real-world outcomes in AYA ALL patients without access to allogeneic transplant are not known, especially in Hispanic/Latino populations. Thus, in order to understand treatment outcomes with modern chemotherapy regimens in this high-risk population, we conducted a retrospective cohort analysis of all AYA ALL patients without access to allogeneic stem cell transplant at a large safety-net hospital. Methods: We conducted a retrospective single-center cohort analysis of ALL patients ages 18 to 39 treated at a large safety-net hospital in Dallas, TX between January 2010 and May 2021. All patients who received induction and consolidation at Parkland Health and Hospital System and did not receive an allogeneic stem cell transplant were included. We interrogated the database for demographic, laboratory, cytogenetic, and next-generation sequencing (using the Foundation Medicine platform) information as well as treatment outcomes and post-relapse therapy. Chemotherapy consisted of either Hyper-CVAD (+/- TKI) or the CALGB 10403 protocol. Data were stored in the RedCap database and SPSS analytical software was used to generate survival analysis and Kaplan-Meier plots. Results: We identified 54 AYA ALL patients during the designated time period, consisting of 36 males and 18 females. The median age of the cohort was 28 years, and 81% of patients were Hispanic. Twelve patients were Ph(+) and 42 patients were Ph(-); 11/12 Ph(+) patients received a TKI with induction and one patient received a TKI beginning with consolidation. Cytogenetic/FISH testing and next-generation sequencing (NGS) were performed in 42 (78%) and 13 (24%) patients respectively, with the most common aberrations noted in Table 1. Of note, NGS was not routinely performed before 2017 at our institution. Six of the 13 patients with NGS results available had Ph-like mutation signatures. The most common induction regimens used were CALGB 10403 (65%), Hyper-CVAD (15%), and Hyper-CVAD + TKI (20%). Forty-one of 49 patients (84%) with a documented day 30 bone marrow biopsy achieved a CR or CR with incomplete count recovery after induction which included 11/12 (92%) Ph(+) patients, 24/31 (77%) Ph(-) patients, and 6/6 (100%) Ph-like patients. Of the patients in CR or CRi at day 30, 27 (50%) were negative for minimal residual disease (MRD) by flow cytometry. Overall survival at 3 years for the entire cohort was 69%, and there was no statistical difference between Ph(+) and Ph(-) patients. Three-year OS was improved in patients who received Hyper-CVAD + TKI (78%) or CALGB 10403 (65%) compared to those who received Hyper-CVAD alone (59%) though this did not reach statistical significance (p=0.72). Conclusions: Our results underscore the ongoing outcomes disparities in the AYA and Hispanic populations, even with the use of modern pediatric-inspired and TKI-containing regimens. The 69% 3-year OS in our population is similar to that in the transplant-eligible AYA population and suggests a diminishing role for allogeneic transplant with current protocols. The high rate of Ph-like signatures on NGS in our population is consistent with the increased prevalence of these mutations in Hispanic ALL patients. Our study is limited as it is a retrospective analysis with a small sample size and represents the results of a single institution. Prospective studies are needed to determine the role of allogeneic transplant in Ph(+) and Ph-like AYA with ALL, and concerted efforts should be made to enroll Hispanic patients in these clinical trials given their high-risk biology and inferior outcomes. Figure 1 Figure 1. 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.

Sign in / Sign up

Export Citation Format

Share Document