Post-Transplant Cyclophosphamide Following a Myeloablative Conditioning For Hematologic Malignancies Receiving An Unmanipulated Haploidentical Bone Marrow Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2103-2103
Author(s):  
Anna Maria Raiola ◽  
Anna Ghiso ◽  
Alida Dominietto ◽  
Carmen Di Grazia ◽  
Francesca Gualandi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Marrow Transplant ◽  
High Dose ◽  
Myeloablative Conditioning ◽  
Post Transplant ◽  
Active Disease ◽  
Related Mortality

Abstract Background Unmanipulated family haploidentical transplants are becoming increasingly used in patients lacking an HLA identical family donor, or a well matched unrelated donor. Aim of the study This is an updated analysis of our program of haploidentical bone marrow transplant (hBMT) , followed by post-transplant high dose cyclophosphamide (PT-CY) in 95 patients with hematoloigic malignancies receiving a myeloablative conditioning. Methods The conditioning regimen consisted of thiotepa, busulfan, fludarabine (TBF) (n=47) , thiotepa melphalan fludarabine (n=5) , or 9.9-12 Gy TBI + fludarabine (n=43). The patients’ median age was 49 years (17-74); the disease status at the time of transplant, was first complete remission (CR1, n=29) , CR2 (n=23), or active disease (n=38,40%). The diagnosis was AML (35%), ALL (24%), MDS (12%) myeloproliferative disorders (12%), other malignancies (17%). The total nucleated cell dose infused was 3.37 (1.4-9.17). The median follow up for surviving patients is 440 days (90-930). Graft versus host disease (GvHD) prophylaxis consisted in PT-CY on day+3 and +5 , cyclosporine (from day 0) , and mycophenolate (from day +1). Results The cumulative incidence of neutrophil (PMN) engraftment was (90%) and all surviving patients on day +30 had full donor chimerism. The median day for neutrophil engraftment was day +17 (11-32). The cumulative incidence (CI) of grade II-III acute GvHD was 14%, and of moderate chronic GvHD 8%, severe cGvHD 9%. The CI of transplant related mortality (TRM) is respectively 7%, 17%, 26% for patients in CR1, CR2, or with active disease. The CI of relapse is respectively 17%, 30%, 37% for patients in CR1, CR2, or with active disease. The overall actuarial survival is respectively 75%, 44%, 32% for patients in CR1, CR2, or with active disease (p=0.002) (Fig.1). The most frequent cause of death was leukemia (26%) followed by infections (9%). Conclusions These data confirm our first report on 50 patients and support the use of myeloablative conditioning regimens, followed by h-BMT with PT-CY. The risk of acute and chronic GvHD seems relatively low , as well as the overall transplant related mortality. We have not seen the excess relapse rate reported when patients are given a non myeloablative regimen, and disease control has been satisfactorily both for patients in remission, as well as for patients with active disease at the time of transplants. Disclosures: No relevant conflicts of interest to declare.

Unmanipulated Haploidentical Bone Marrow Transplantation and Post-Transplant Cyclophosphamide for Hematologic Malignanices Following A Myeloablative Conditioning.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3034-3034
Author(s):  
Andrea P Bacigalupo ◽  
Anna Maria Raiola ◽  
Alida Dominietto ◽  
Maria Teresa Van Lint ◽  
Francesca Gualandi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Myeloablative Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Active Disease ◽  
Related Mortality

Abstract Abstract 3034 Despite a large number of unrelated donors (UD), not more than 30% of patients who have activated a donor search, undergo an allogeneic UD stem cell transplant. HLA haploidentical family members are being increasingly considered as an alternative donors, both using T cell depleted or T cell replete grafts. Post-transplant high dose cyclophosphamide (PT-CY), introduced by the Baltimore group, has shown very promising results following non myeloablative conditioning regimens. We are now reporting 50 patients with high risk hematologic malignancies, who received a myeloablative regimen, followed by unmanipulated haploidentical bone marrow transplant (hBMT) and PT-CY. The myeloablative conditioning consisted of thiotepa (10 mg/kg), busulfan (9,6 mg/m2̂), fludarabine (150 mg/m2̂)(n=35), or total body irradiation (9,9–12 Gy), fludarabine (120 mg/m2̂) (n=15). The median age was 42 years (18–66); 23 patients were in remission and 27 had active disease; 10 patients were receiving a second allograft. Graft versus host disease (GvHD) prophylaxis consisted in PT-CY on day+3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median nucleated cell dose was 3.6 ×108̂/kg (range: 1,4 – 7,7). The median time to neutrophil counts of >0.5×109/L was 18 days (range, 13–30 days) and to platelet counts of >20×109/L 23 days (range, 14 – 58 days), respectively. There was no correlation between infused number of nucleated cells and days of neutrophil engraftment. The cumulative incidence of engraftment was 90%for neutrophils and 86% for platelets. Three patients died before engraftment, and 2 patients had autologous recovery: 45 patients (90%) had full donor chimerism on day +30. The cumulative incidence of grade II-III acute GvHD was 12%, and of moderate chronic GvHD 10%. With a median follow up for surviving patients of 333 days (149–623), the cumulative incidence of transplant related mortality is 18%, and the rate of relapse 26%. The actuarial 22 months disease free survival is 68% for patients in remission and 37% for patients with active disease (p<0.001). Causes of death were pneumonia (n=3), haemorrhage (n=3), sepsis (n=3) and relapse (n=7). In conclusion, a myeloablative conditioning regimen followed by h-BMT with PT-CY, results in a low risk of acute and chronic GvHD and encouraging rates of transplant related mortality and disease free survival. Disclosures: No relevant conflicts of interest to declare.

Bone Marrow Transplant Activity - A Country Report from Pakistan.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5038-5038
Author(s):  
Khalil Ullah ◽  
Tahir S. Shamsi ◽  
Salman N. Adil
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Transplant ◽  
Graft Failure ◽  
Marrow Transplant ◽  
Histopathological Analysis ◽  
Country Report ◽  
Post Transplant ◽  
Transplant Centre ◽  
Related Mortality

Abstract Bone Marrow transplant activity started in 1999 in Pakistan when Bismillah Taqee Institute of Health Sciences & Blood Diseases Centre started functioning in the southern port city of Karachi, Pakistan. Two years later in year 2001 Armed Forces Bone Marrow Transplant Centre started functioning in the northern part of country, Rawalpindi, Pakistan. In 2004 another transplant centre, started in Aga Khan University Hospital, Karachi, Pakistan. Since the establishment of these transplant centers a total of 349 allogeneic transplants have been carried out for various hematological disorders. The major indications included aplastic anaemia (n=166), β-Thalassaemia major (n=76), chronic myeloid leukaemia (n=57), acute leukaemias (n=37) and misc disorders including MDS, Fanconi anaemia and others (n=13). A total of 22 autologous transplants in lymphomas and multiple myeloma have also been carried out. Since this number is very small, only data of allogeneic transplants is being presented here. Major post transplant complications encountered were neutropenic fever in 92.6% patients with 27% culture positivity (412/1571). Infective complications included bacterial infections (both gram+ive and gram-ive) in 194 patients (56%), fungal infection in 32 patients (10%), CMV infection in 15 patients (5%), herpes infection in 16 patients (5%), tuberculosis in 9 patients (3%) and PCP in 1 patient (0.28%) and malaria in 1 patient (0.28%). So post transplant infections were confirmed in 76.6% (268/349) patients on the basis of clinical assessment, microbiological, virological and histopathological analysis. Non infective post transplant complication included aGvHD (grade II-IV) in 80 patients (23%), cGvHD 46 patients (13.1%), VOD liver in 25 patients (7.2%), haemorrhagic cystitis in 27 patients (7.7%), ARF in 13 patients (3.7%), primary graft failure in 5 patients(1.4%), graft rejection in 17 patients (4.9%) and relapse in 14 patients (4%). Transplant related mortality was observed in 93 patients (26.6%). Infective & non infective causes of mortality included septicemia in 15 patients (4.3%), CMV in 8 patients (2.3%), fungal infections in 8 patients (2.3%), tuberculosis in 2 patient (0.6%). herpes encephalitis in 1 patient (0.3%) VOD in 8 patients (2.3%), aGvHD in 12 patients (3.4%), cGvHD in 7 patients (2.0%), ARF in 8 patients (2.3%) and intracranial haemorrhage in 3 patients (0.9%). Graft related mortality due to graft failure and relapse was observed in 6 patients (1.7%) and 14 patients (4%) respectively. Unrelated accidental death in 1 patient (0.3%). Overall survival was observed in 256 patients (73.3%) and DFS in 250 patients (71.6%). The OS and DFS was 72.7% and 70.9% in BTIHS & BDC patients, whereas OS & DFS was 72.8% and 70.7% respectively in AFBMTC patients. The OS & DFS was 82.6% at AKUH. Disease wise overall survival in aplastic anemia, β-Thalassaemia, CML and acute leukemia was 78.3%, 76.3%, 63.1% and 59.5% respectively.

scholarly journals Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 575-579 ◽  
Author(s):  
JY Cahn ◽  
M Labopin ◽  
F Mandelli ◽  
AH Goldstone ◽  
K Eberhardt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Marrow Transplant ◽  
Acute Myeloblastic Leukemia ◽  
High Dose ◽  
First Remission ◽  
Autologous Bone ◽  
Related Mortality

Abstract High-dose chemotherapy, with or without radiotherapy, followed by autologous stem-cell rescue is used increasingly for the intensification of first remission in acute myeloblastic leukemia (AML). However, these treatments have been limited to young patients due to the increased risks of regimen-related toxicities and mortality with age. Several investigators have recently published the upper age limit for autologous bone marrow transplant (ABMT) in AML because of encouraging results. The results of ABMT for AML were studied in 111 patients > or = 50 years of age intensified in first remission. Median age at transplant was 53 years (range, 50 to 63 years). Fifty patients were conditioned with total body irradiation and 61 with polychemotherapy: 23 with busulfancyclophosphamide, 11 with the University College Hospital (UCH; London, UK) regimen, 6 with BAVC, and 21 with various other treatments. Marrow was purged in only 11 cases. Results were compared with 786 ABMTs performed for AML in patients between 16 and 49 years of age (median, 35 years). For AML in first remission, the probability of leukemia-free survival (LFS) at 4 years was 34% +/- 5% for patients aged 50 years or more and 43% +/- 2% for patients less than 50 years of age (P = .004), with a survival probability of 35% +/- 6% and 48% +/- 2%, respectively (P = .004). The probability of relapse was not significantly different between the two groups (52% +/- 7% v 50% +/- 2%), but transplant-related mortality was significantly higher in the older age group (28% +/- 5% v 14% +/- 2%; P < .0001) and mainly due to infectious complications. In a multivariate analysis, age less than 50 years was a favorable risk factor for LFS, treatment-related mortality (TRM), and survival but not for relapse incidence. These data suggest that ABMT should be considered in older AML patients.

scholarly journals Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 575-579 ◽  
Author(s):  
JY Cahn ◽  
M Labopin ◽  
F Mandelli ◽  
AH Goldstone ◽  
K Eberhardt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Marrow Transplant ◽  
Acute Myeloblastic Leukemia ◽  
High Dose ◽  
First Remission ◽  
Autologous Bone ◽  
Related Mortality

High-dose chemotherapy, with or without radiotherapy, followed by autologous stem-cell rescue is used increasingly for the intensification of first remission in acute myeloblastic leukemia (AML). However, these treatments have been limited to young patients due to the increased risks of regimen-related toxicities and mortality with age. Several investigators have recently published the upper age limit for autologous bone marrow transplant (ABMT) in AML because of encouraging results. The results of ABMT for AML were studied in 111 patients > or = 50 years of age intensified in first remission. Median age at transplant was 53 years (range, 50 to 63 years). Fifty patients were conditioned with total body irradiation and 61 with polychemotherapy: 23 with busulfancyclophosphamide, 11 with the University College Hospital (UCH; London, UK) regimen, 6 with BAVC, and 21 with various other treatments. Marrow was purged in only 11 cases. Results were compared with 786 ABMTs performed for AML in patients between 16 and 49 years of age (median, 35 years). For AML in first remission, the probability of leukemia-free survival (LFS) at 4 years was 34% +/- 5% for patients aged 50 years or more and 43% +/- 2% for patients less than 50 years of age (P = .004), with a survival probability of 35% +/- 6% and 48% +/- 2%, respectively (P = .004). The probability of relapse was not significantly different between the two groups (52% +/- 7% v 50% +/- 2%), but transplant-related mortality was significantly higher in the older age group (28% +/- 5% v 14% +/- 2%; P < .0001) and mainly due to infectious complications. In a multivariate analysis, age less than 50 years was a favorable risk factor for LFS, treatment-related mortality (TRM), and survival but not for relapse incidence. These data suggest that ABMT should be considered in older AML patients.

Adverse reactions related to i.v. infusion of high-dose cyclophosphamide in bone marrow transplant patients

1994 ◽  
Vol 51 (19) ◽  
pp. 2419-2421
Author(s):  
Terry L. Schwinghammer ◽  
Laura E. Wiggins ◽  
Mary Reilly Burgunder ◽  
Terri E. Michell ◽  
William L. Bailey
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Adverse Reactions ◽  
Marrow Transplant ◽  
High Dose ◽  
Transplant Patients

Utility of WT1 as a Reliable Tool for the Detection of Minimal Residual Disease in Children with Leukemia

2002 ◽  
Vol 5 (3) ◽  
pp. 269-275 ◽  
Author(s):  
Morris Kletzel ◽  
Marie Olzewski ◽  
Wei Huang ◽  
Pauline M. Chou
Keyword(s):  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Bone Marrow Transplant ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Marrow Transplant ◽  
Post Transplant ◽  
High Level ◽  
Minimal Residual

WT1 encodes a transcription factor involved in the pathogenesis of Wilms' tumor. A high level of expression has been reported in blasts from patients with various hematological malignancies. The study was performed to evaluate the utility of monitoring WT1 expression in children with leukemia at diagnosis, during therapy, and following bone marrow transplant. We tested a total of 204 samples prospectively. These included samples from patients with the following diagnoses: acute lymphoblastic leukemia (ALL) at diagnosis ( n = 45), at relapse ( n = 14), and in remission ( n = 45); acute non-lymphoblastic leukemia (ANLL) at diagnosis ( n = 14), at relapse ( n = 5), and in remission ( n = 12); and chronic myelogenous leukemia (CML) in blast crisis ( n = 1) and in chronic phase ( n = 1). A total of 33 of these patients were transplanted: 19 ALL, 12 ANLL, and 2 CML. In addition, samples from 5 patients with aplastic anemia and 28 controls were obtained from peripheral blood ( n = 17), cord blood ( n = 3), and bone marrow ( n = 8). Primer pairs were designed to locate specific nucleotide sequences for mRNA of WT1. RT-PCR was performed in all samples and compared with K562 cells from ATCC (defined as 1.0) as positive control. A positive test was arbitrarily defined as WT1/K562 > 0.5. Samples at diagnosis and relapse, including 56 out of 59 ALL (95%), 26 ANLL (100%), and 1 CML in blast crisis, demonstrated high levels of WT1 expression. In contrast, only 5 of 90 samples obtained in remission or post-transplant showed high levels of WT1 expression ( P < 0.0001; 95% CI = 0.66–0.94). The five patients with high WT1 expression during follow-up relapsed within 2 to 6 months. In conclusion, we have found that WT1 is consistently elevated in children with leukemia. Significant differences in the level of WT1 expression were noted between these patients during diagnosis and at relapse, and those during remission. More importantly, following bone marrow transplant, a significant high level of WT1 expression preceded clinical relapse by 2 to 6 months. Therefore, WT1 is a reliable marker for monitoring minimal residual disease during therapy as well as in the post-transplant period.

Sign in / Sign up

Export Citation Format

Share Document