Marrow transplant experience in children with acute lymphoblastic leukemia: An analysis of factors associated with survival, relapse, and graft-versus-host disease

1985 ◽  
Vol 13 (4) ◽  
pp. 165-172 ◽  
Author(s):  
Jean E. Sanders ◽  
Nancy Flournoy ◽  
E. Donnall Thomas ◽  
C. Dean Buckner ◽  
Lawrence G. Lum ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Graft Versus Host Disease ◽  
Lymphoblastic Leukemia ◽  
Marrow Transplant ◽  
Host Disease ◽  
Graft Versus Host ◽  
Factors Associated

scholarly journals Ponatinib-Induced Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia without the T315I Mutation Relapsing after Allogeneic Transplant

Chemotherapy ◽  
2017 ◽  
Vol 62 (6) ◽  
pp. 353-356 ◽  
Author(s):  
Annamaria Petrungaro ◽  
Massimo Gentile ◽  
Carla Mazzone ◽  
Rosa Greco ◽  
Giuseppina Uccello ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Graft Versus Host Disease ◽  
Lymphoblastic Leukemia ◽  
Salvage Chemotherapy ◽  
Cell Transplant ◽  
Host Disease ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
T315i Mutation ◽  
Graft Versus Leukemia Effect

We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i.v., days 1-5, cyclophosphamide 700 mg i.v., days 1-5, and ponatinib 45 mg p.o., daily starting at day 15). We observed a rapid decrease in minimal residual disease on molecular assessment with an MMR of P190-BCR-ABL/ABL = 0.01% confirmed by bone marrow revaluations at days +23, +59, +108, and +191 after the first day of salvage chemotherapy. After starting ponatinib, the patient experienced skin graft-versus-host disease, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib treatment was well tolerated and considered safe with easily manageable side effects.

The significance of graft-versus-host disease and pretransplantation minimal residual disease status to outcome after allogeneic stem cell transplantation in patients with acute lymphoblastic leukemia

Blood ◽  
2001 ◽  
Vol 98 (6) ◽  
pp. 1982-1985 ◽  
Author(s):  
Mehmet Uzunel ◽  
Jonas Mattsson ◽  
Marie Jaksch ◽  
Mats Remberger ◽  
Olle Ringdén
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Minimal Residual

Abstract Relapse is the major cause of treatment failure after allogeneic stem cell transplantation (SCT) in patients with acute lymphoblastic leukemia. Minimal residual disease (MRD) was analyzed before SCT in 30 patients with acute lymphoblastic leukemia. The aim was to determine whether the level of MRD before transplantation was correlated with outcome. Fifteen patients were found to have high-level MRD (10−2 to 10−3), 10 had low-level MRD (< 10−3), and 5 were MRD−. Among MRD− patients the probability of relapse was 0 in 5, which was less than in MRD+ patients (13 of 25) (P = .05). No major difference was found between the high- and low-level MRD+ groups. Among the MRD+ patients, only 2 of 11 with acute and chronic graft-versus-host disease had a relapse, versus 11 of 14 without (P = .005). In conclusion, for patients entering transplantation while they have residual disease, a combination of acute and chronic graft-versus-host disease may be needed to decrease the risk of relapse after SCT.

scholarly journals Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant

Chemotherapy ◽  
2016 ◽  
Vol 62 (1) ◽  
pp. 58-61 ◽  
Author(s):  
Daniela Renzi ◽  
Francesco Marchesi ◽  
Gottardo De Angelis ◽  
Loredana Elia ◽  
Emanuela Salvatorelli ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Graft Versus Host Disease ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplant ◽  
Standard Dosage ◽  
Host Disease ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
T315i Mutation ◽  
Graft Versus Leukemia Effect

We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.

scholarly journals Risk factors associated with increased nonrelapse mortality and with poor overall survival in children with chronic graft-versus-host disease

Blood ◽  
2011 ◽  
Vol 118 (16) ◽  
pp. 4472-4479 ◽  
Author(s):  
David A. Jacobsohn ◽  
Mukta Arora ◽  
John P. Klein ◽  
Anna Hassebroek ◽  
Mary E. Flowers ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Graft Versus Host Disease ◽  
Marrow Transplant ◽  
Peripheral Blood Cell ◽  
Family Counseling ◽  
Poor Overall Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Factors Associated

Abstract There is a paucity of information regarding the factors that affect nonrelapse mortality (NRM) and overall survival among children that develop chronic graft-versus-host disease (cGVHD). We performed multivariate analyses using data from the Center for International Blood and Marrow Transplant Research to identify risk factors for NRM and survival in 1117 pediatric subjects with leukemia or myelodysplastic syndrome, transplanted from related donors, unrelated donors (URD), or unrelated cord blood between 1995 and 2004. We identified 4 variables associated with higher NRM: HLA partially matched or mismatched URD, peripheral blood cell graft, Karnofsky/Lansky score < 80 at cGVHD diagnosis, and platelets < 100 × 109/L at cGVHD diagnosis. Factors associated with significantly worse survival were: age > 10 years, transplantation from HLA partially matched or mismatched URD, advanced disease at transplantation, Karnofsky/Lansky < 80; and platelets < 100 × 109/L. Cumulative incidence of discontinuation of systemic immune suppression at 1, 3, and 5 years after diagnosis of cGVHD were 22% (20%-25%), 34% (31%-37%), and 37% (34%-40%), respectively. This is the largest study elucidating variables affecting outcome after diagnosis of cGVHD in pediatric allograft recipients. These variables may be useful for risk stratification, development of future clinical trials, and family counseling in children with cGVHD.

Sign in / Sign up

Export Citation Format

Share Document