Haploidentical Unmanipulated G-CSF-Primed Peripheral Blood Stem Cell Transplantation for Patients with High-Risk Hematologic Malignancies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4365-4365
Author(s):  
Dai-Hong Liu ◽  
Li Yu ◽  
Wenrong Huang ◽  
Liping Dou ◽  
Honghua Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Continuous Line ◽  
Free Survival ◽  
Grade 3

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an effective, even curative, treatment for patients with high-risk hematologic malignancies. Transplantation from haploidentical donors (haplo-HCT) has been applied for the treatment of hematologic malignancies within the past 2 decades. Bone marrow (BM), G-CSF-primed peripheral blood stem cells (PBSCs), G-CSF-primed BM (G-BM) or the combination of PBSCs and G-BM can serve as stem cell sources for allo-HCT. The optimal source of stem cells in cases of haplo-HCT without ex vivo TCD under myeloablative conditioning is not yet clear. Therefore, we initiated a study of unmanipulated haplo-HCT from PBSCs (haplo-PBSCT) for the treatment of high-risk hematologic malignancies. In this report, we analyzed 89 adult patients who received consecutive haplo-PBSCT to evaluate the efficacy and safety of this transplantation procedure. PATIENTS AND METHODS Eighty-nine patients received consecutive haploidentical allo-PBSCT between July, 2007 ¨C June, 2014 at the Chinese PLA General Hospital, Beijing, China (Table 1). PBSCs were freshly isolated and infused into the recipients. The conditioning regimen consisted of Bu (3.2 mg.kg-1.d-1 intravenously, days -10 to -8), Carmustine, 250 mg.m-2, day -5), cytarabine (4 g.m-2.d-1, days -7 to -6), cyclophosphamide (60mg kg-1.d-1, days -4 to -3), and ATG (Thymoglobuline, rabbit; 2.5 mg.kg-1.d-1, days -5 to -2). All transplant recipients received CsA, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. "High-risk'' hematologic malignancies were defined as: 1) AL with the [t(9;22)(q34;q11)], Flt3-ITD mutation, mixed lineage leukemia genes and complex cytogenetics regardless of disease stage; 2) AML-CR1 after 3 or more cycles of induction, ALL-CR1 after 4 weeks of induction or AL-CR1 with positive MRD after 2 cycles of consolidation; 3) AL beyond CR2 or in non-remission (NR) regardless of cytogenetics, or CML beyond CP1; and 4) T cell lymphoblastic lymphoma in CR and T cell lymphoma resistant to chemotherapy or autologous transplantation. The endpoint of the last follow-up for all surviving patients was January 31, 2015. RESULTS Sustained myeloid engraftment with full donor chimerism was achieved in 89 patients (100%) at a median of 16 (10 - 26) days. Eighty patients (89.9%) achieved platelet recovery in a median of 28 (10 - 207) days. The occurrence of GVHD was showed in Fig 1. The 3-year of cumulative incidence of transplant-related mortality was 23.4% ± 5.4%. Non-remission status prior to transplant was found to be significantly correlated with relapse (P = 0.006, odds ratio [OR] = 3.17), leukemia-free survival (P = 0.013, OR = 2.48) (Fig. 2) and overall survival (P = 0.03, OR = 2.27). CONCLUSION The results described rapid and complete neutrophil engraftment, a low incidence of grade 3-4 GVHD and promising survival in patients with high-risk hematologic malignancies. It demonstrated the reliability of G-CSF-primed PBSCs as a graft source in unmanipulated haplo-HCT under myeloablative conditioning. Table 1. Patient and donor characteristics Cases % Gender, n (%) Male 69 77.5 Age, y, median(range) Patient <46 y, n (%) 28(6-59) Donor >40 y, n (%) 38(9-61) Hematologic malignancy, n (%) AML 51 57.3 CR1 CR2* 23 3 NR*/beyond CR2 23/1 ALL 20 22.5 CR1 CR2 10 7 NR 3 CML 5 5.6 CP1* 2 AP/CP2 1/2 Lymphoma 13 14.6 CR 5 Resistant 8 Donor/recipient relationship, n (%) Parent 47 52.8 Sibling 26 29.2 Child 12 13.5 Lateral relative 4 4.5 No. of HLA antigens (A/B/DR) mismatched, n(%) 1 18 20.2 2 25 28.1 3 46 51.7 Second HCT 9 10.1 Graft: MNC (108/kg) 11.04 (5.64-36.46) CD34+ (106/kg) 5.83 (2-23.73) Figure 1. Acute and chronic GVHD. (A) CI (Cumulative Incidence) of grade 2-4 (continuous line) and grade 3-4 (dotted line) acute GVHD. (B) CI of total (continuous line) and moderate to severe (dotted line) chronic GVHD. Figure 1. Acute and chronic GVHD. (A) CI (Cumulative Incidence) of grade 2-4 (continuous line) and grade 3-4 (dotted line) acute GVHD. (B) CI of total (continuous line) and moderate to severe (dotted line) chronic GVHD. Figure 2. Disease-free survival according to disease status. Figure 2. Disease-free survival according to disease status. Disclosures No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5054-5054
Author(s):  
Amir Peyman ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Louis Fernandez ◽  
Donna L. Forrest ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

Chronic Graft Versus Host Disease and Pretransplant Disease Status Predict Outcomes in Patients with Hematologic Malignancies Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5090-5090
Author(s):  
Megha A. Shah ◽  
Mounzer Agha ◽  
Markus Mapara ◽  
Kate Lenhart ◽  
Anastasios Raptis
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Free Survival ◽  
Effective Treatment Modality ◽  
Disease Free ◽  
Reduced Intensity

Abstract Reduced intensity stem cell transplantation (SCT) is an effective treatment modality for patients with hematologic malignancies who are not candidates for conventional myeloablative SCT. We conducted a retrospective review of all patients with hematologic malignancies receiving a reduced intensity allogeneic SCT from July 2002 to July 2007. Data pertaining to patient demographics, engraftment, disease status pre and post transplant, graft versus host disease (GVHD), and HLA matching was analyzed to identify factors significantly affecting the clinical outcome. Seventy three patients, with a median age of 55 (range of 19–70) and with the diagnoses of ALL (n=8), AML (n=30), CLL (n=3), CML (n=1), Hodgkin’s (n=7), non-Hodgkin’s (n=7), MDS (n=11), and MM (n=6) underwent a reduced intensity SCT using a fludarabine based conditioning regimen. Thirty nine (53%) received unrelated donor grafts and 34 (47%) received sibling donor grafts. Fifty six patients (77%) received fully matched grafts whereas 17 patients (23%) had an antigen or allele mismatch. Acute GVHD grade II-IV was observed in 27 of the 73 patients and chronic GVHD was seen in 18 of the 48 patients who could be evaluated. Seventeen patients developed transplant related fatal complications and 30 patients died from disease progression or relapse. Median time to neutrophil recovery was 15 days (range of 9–41 days) and median time to platelet recovery was 18 days (range of 9–42 days). Graft failure was observed in 6 of the 73 patients. Median overall survival and disease free survival for all patients was 7.7 and 6.6 months respectively. Median overall survival for patients with persistent disease or in remission at the time of the SCT was 5.6 and 21.8 months (p= 0.01) while that for disease free survival was 5.7 and 8.4 months (p=0.06). Median overall survival with and without chronic GVHD was 25.6 and 9.4 months (p <0.0001) while median disease free survival was 18.2 and 6.0 months (p< 0.0001). Patients with limited chronic GVHD have not yet reached median overall survival while the median disease free survival was 18.4 months. Those with no or extensive chronic GVHD had medians of 9.4 and 9.2 months for overall survival and 6.0 and 9.2 months for disease free survival (p= 0.004 and p=0.02). The source of the stem cells as well as the administration of allele or single antigen mismatch grafts did not affect the outcome. Reduced intensity SCT is an effective treatment modality in patients with hematologic malignancies, though it is most effective in patients who are in remission at the time of transplant and should be offered in this setting. Patients with limited chronic GVHD had a better outcome suggesting the presence of potent anti-tumor activity of the donor immune competent cells without the detrimental effects in clinical outcome caused by extensive chronic GVHD.

Disease-Free Survival Of Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation Is Not Associated With Disease Status and Donor Sources

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2158-2158
Author(s):  
Yue Lu ◽  
Tong Wu ◽  
Xing-Yu Cao ◽  
Yan-Li Zhao ◽  
De-Yan Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Disease Status ◽  
Refractory Anemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free ◽  
Related Mortality

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is an only curative modality currently for myelodysplastic syndrome (MDS). High-risk MDS usually has lower complete remission (CR) rate and higher chemotherapy-related mortality compared with de novo acute myeloid leukemia (AML). To examine whether CR before HSCT has survival benefit for MDS treated by HSCT, we retrospectively analyzed the data during 11 years from our center. The clinical outcomes of MDS after HSCT from different donor sources have also been evaluated. Objective In present clinical study, the effects of disease status and donor sources on disease-free survival (DFS) of MDS after HSCT were studied. Methods From August 2001 to December 2012, total 122 patients with MDS that underwent HSCT in our center were enrolled. Male to Female was 76: 46. The median age was 35 (8 to 57) years old. The median blasts in bone marrow (BM) before conditioning were 9% (1% to 65%). According to 2008 WHO classification, the patients were diagnosed as refractory cytopenias with unilineage dysplasia (RCUD) in 12, refractory anemia with ring sideroblasts (RARS) in 2, 5q- in 1, refractory cytopenias with multilineage dysplasia (RCMD) in 15, refractory anemia with excess blasts (RAEB) -1/RAEB-2 in 36 and transformed AML in 56. For International Prognostic Scoring System (IPSS), 12 patients were in low-risk, 27 in intermediate-1, 24 in intermediate-2, and 59 in high-risk. Based on BM blast percentage pre-conditioning, 47 cases were less than 5%, 43 patients were between 5% to 20%, and 32 cases were more than 20%. The stem cells were from identical siblings (45) or unrelated donor (24) or haploidentical family members (53). Conditioning regimens were BUCY/BUFLU for identical sibling HSCT, and BUCY/BUFLU plus ATG (Thymoglobuline, 8-10mg/kg) for unrelated or haploidentical transplants. Graft-versus-host disease prophylaxis was employed by Cyclosporin A, Methotrexate and Mycophenolate mofetil as reported previously (DP Lu et al., Blood 2006; 107:3065). Results: With median follow-up 31 (1-144) months, DFS was 73.8%. Fourteen patients (11.4%) relapsed. Transplant-related mortality was 14.8%. No significant differences on DFS were found among RCUD/RARS/5q- (68.8%), RCMD (85.7%), RAEB-1/RAEB-2 (72.2%) and transformed AML (73.2%) (p=0.761). A similar DFS was seen in different risk categories (73.3% in low-risk, 79.2% in intermediate-1, 75.0% in intermediate-2 and 71.2% in high-risk; p=0.861). Moreover, CR or not before HSCT has no remarkable effect on DFS (blasts <5%, 78.7%; blasts 5% to 20%, 67.4%; blasts > 20%, 75.0%; p=0.342). Donor sources have also no significant effects on DFS (identical sibling 75.6%, unrelated donor 79.2%, haploidentical family member 69.8%; p=0.651). Conclusions Our clinical results have shown that under current protocol, DFS of MDS after allogeneic HSCT is quite encouraging no matter the disease status and stem cell donor sources. Therefore, it is not necessary that complete remission is achieved by chemotherapy before transplant. Haploidentical family member is an important alternative donor for patients with MDS when matched either identical sibling or unrelated donor is not available. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation In Chronic Myeloid Leukemia In TKIs Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5554-5554
Author(s):  
Parvez Ahmed ◽  
Syed Karman Mahmood ◽  
Tariq Mahmood Satti ◽  
Qamar Un Nisa Chaudhry ◽  
Nighat Shahbaz ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Treatment Option ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Standard Risk ◽  
Disease Free

Abstract Introduction Tyrosine kinase inhibitors (TKIs) have largely replaced allogeneic hematopoietic stem cell transplantation (HSCT) as first line treatment option in chronic phase chronic myeloid leukemia (CML) yet due to the need for continued administration the cost becomes prohibitive in majority of patients without any health insurance coverage. Therefore allogeneic stem cell transplant remains a reasonable treatment option for such patients especially in resource constrained countries. It is also useful treatment modality in children, CML in accelerated phase and in patients intolerant to TKIs. We report results of 64 consecutive patients undergoing HLA matched sibling allo HSCT at our center from April 2002 to September 2012. Methods Patients with Philadelphia positive CML were categorized into standard and high risk based on age >40 years, disease duration > 12 month from diagnosis to transplant and accelerated phase. Conditioning regimens used were oral busulphan 16 mg/kg plus cyclophosphamide 200 mg/kg (Bu16/Cy200), Bu16/Cy120, Bu16/Cy120/Etoposide30 and Bu16/Cy120/ATG. Source of stem cell was peripheral blood stem cells (PBSC) or bone marrow (BM) infusion. GVHD prophylaxis consisted of ciclosporin, short methotrexate (10 mg/m2 on day +1, 8 mg/m2 on day +3 & 6) ± prednisolone. Statistical calculations included Fisher’s exact test, Kaplan-Meier for survival analysis, and Cox regression for multivariate analysis. Results Median age of the patients was 28 years (range 7 – 54). Female donor to male recipient was seen in 12 cases while 20 patients had major blood group mismatch. Forty seven patients were standard risk while 17 were categorized as high risk. Bu16/Cy120 was the most common conditioning regimen given in 34 cases followed by Bu16/Cy200 in 19 cases. Fifty four patients received PBSC while BM was given in 8 cases. Grade I/II acute GVHD was seen in one-third of the cases while 7 (11%) had grade III/IV GVHD. Extensive chronic GVHD was seen in 10 (16%) cases while 12 (19%) patients had limited chronic GVHD. Complications observed were hemorrhagic cystitis (7), VOD (4), CMV infection (2) and septicemia (3). Five (8%) patients had disease relapse. The overall survival was 70.3% (median 1627 days) while disease free survival was 62.5% (median 1547 days). Nineteen patients died of various complications like extensive GVHD (n=5), septicemia (n=3), VOD (n=3), CMV infection (n=3) and disseminated aspergillosis (n==2). A significant difference was observed among patients bearing standard risk compared with those in high risk group in terms of overall survival (79% versus 47% , p=0.013), disease free survival (72% versus 35%, p=0.031) and incidence of acute GVHD (34% versus 71%, p=0.01) in univariate analysis. Age >40 year was the only factor associated with adverse outcome in multivariate Cox-regression model. Conclusions Early allogeneic HSCT in CML patients <40 years of age is associated with long term disease free survival in about 70% of cases. It is a reasonable treatment option in situations where TKIs cannot be employed as first line therapy due to various reasons. Disclosures: No relevant conflicts of interest to declare.

Second Allogeneic Stem Cell Transplantation for Hematologic Malignancies Using Chemotherapy Only Cytoreduction with Clofarabine, Melphalan, and Thiotepa

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3942-3942
Author(s):  
Barbara Spitzer ◽  
Miguel-Angel Perales ◽  
Nancy A. Kernan ◽  
Susan E. Prockop ◽  
Nicholas Webb ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Off Label ◽  
Grade 3 ◽  
Disease Free ◽  
Related Mortality ◽  
Neutrophil Engraftment

Abstract Background:Allogeneic hematopoietic stem cell transplantation (alloHSCT) plays an important role in the treatment of patients with high-risk hematologic malignancies. However, relapse of disease remains the primary cause of mortality post HSCT. Treatment options for these patients remain limited, and outcomes after salvage attempts are often poor, due to both increased toxicity and high rates of relapse. We describe a chemotherapy-only cytoreductive regimen consisting of clofarabine (Clo), melphalan (Mel) and Thiotepa (Thio) for the treatment of patients undergoing a second or third HSCT (HSCT2 or HSCT3). Methods: Between November 2005 and December 2012, 19 patients with hematologic malignancies who had relapsed after prior alloHSCT received a HSCT2 (N=17) or HSCT3 (N=2) using this regimen. There were 12 males and 7 females aged 4.5-44 years (median 20.2 years). Diagnoses and stages at the time of HSCT2/3 included: ALL in second complete remission (CR2; N=4) or CR3 (N=8); AML in CR2 (N=2) or CR3 (N=4); and CML in 2nd chronic phase (N=1). Seven patients had extramedullary disease, including CNS (N=5), testicle (N=1), and bone (N=1). Time to relapse following prior HSCT was 0-6 months (N=6), 6-12 months (N=7), or >12 months (N=6). Median time between most recent and present HSCT was 15 months (range 8.5 – 225 months). Thirteen patients received allografts from the same donor used for prior alloHSCT, while 6 pts received allografts from different donors. Grafts comprised conventional/unmodified marrow (cBMT) (N=7), peripheral blood (cPBSCT) (N=6), double umbilical cord blood units (N=1), or T-cell depleted (TCD) PBSCT (N=5). Cytoreduction included Clo 20 (N=18) or 30 (N=1) mg/m2/dose x 5, Thio 10 mg/m2 x 1, and Mel 70 mg/m2/dose x 2. GvHD prophylaxis included tacrolimus + methotrexate or mycophenolate for the unmodified grafts, while recipients of TCD grafts received ATG only pre-transplant for rejection prophylaxis. TCD was achieved by CD34+ selection, with the addition of E-rosetting in one case. All patients received filgrastim from day +7 until neutrophil engraftment. Results: Neutrophil engraftment occurred in all patients at a median of 12 days (range 9-25). Platelet recovery occurred in 17 evaluable patients at a median of 22 days (range 14-98). Transplant related mortality was limited to 2 patients, one who died of veno-occlusive disease 27 days post-transplant and the other of EBV lymphoma 11 weeks post-transplant. Neither of these patients recovered their platelet counts. Regimen related toxicity included: grade 3-4 mucositis (N=5), grade 4 renal toxicity (N=2), grade 3-4 hypoxia (N=3). Fifteen patients developed grade 3-4 transaminitis beginning immediately following clofarabine administration, which completely resolved in 14/15 cases. Five patients, all recipients of unmodified grafts, developed grade 2-4 acute GvHD, two of whom developed chronic GvHD; one patient who received a cPBSCT developed de novo chronic GvHD. Seven patients relapsed at a median of 14.6 months (range: 3.5-25.3 months) post-HSCT2/3, and all died of their disease. Ten of 19 patients are alive and disease free with median follow-up of 50.1 months (range 22.8-90.4). Overall and disease-free survival probabilities were 51.5% and 52.6% respectively. There were no statistically significant difference in OS or DFS for the following factors: (1) patient age < or ≥ 21 years, (2) grafts from same or different donor, (3) myeloid vs. lymphoid disease, (4) CR2 vs. CR3 at HSCT, (5) TCD vs. unmodified grafts. Outcome was significantly superior for patients whose relapse occurred > 6 months from prior HSCT, with an OS of 75.2% compared with 0% (p<0.0001) in patients whose relapse was ≤ 6 months. Of the 6 patients who received HSCT2/3 for relapse within 6 months of their first HSCT, 4 died from relapse, and 2 died from transplant related mortality. Conclusions: This cytoreductive regimen has allowed secondary transplants in a cohort of high-risk patients with ALL and AML who relapsed following a prior transplant using various graft and donor options. Overall, the regimen is well tolerated and has yielded promising results, specifically in patients who relapse more than 6 months from their prior transplant. This salvage treatment merits further study and evaluation in collaborative group studies. Disclosures Off Label Use: Clofarabine, melphalan, and thiotepa all off label for bone marrow transplant.. Boulad:Genzyme Sanofi: Trials partially funded by Genzyme Sanofi Other.

Stem-Cell Transplantation in Adults with Philadelphia-Negative High-Risk Acute Lymphoblastic Leukemia in First Complete Remission: A Prospective Multicenter Trial Comparing Haploidentical Donors with Identical Sibling Donors

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 62-62 ◽  
Author(s):  
Yu Wang ◽  
Wu Depei ◽  
Qifa Liu ◽  
Lan-Ping Xu ◽  
Xiao-Hui Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Patient Age ◽  
Free Survival ◽  
Patient Âgé ◽  
Disease Free ◽  
First Complete Remission

Abstract Purpose and design The effect of HLA-identical sibling donor (ISDs) haematopoietic stem cell transplantation (HSCT) on adults with high-risk acute lymphoblastic leukaemia (ALL) in the first complete remission (CR1) has been established. Our recent single-institute, retrospective study showed that haploidentical HSCT was superior to chemotherapy alone for patients with high-risk ALL in CR1. To test the hypothesis that haploidentical HSCT would be a valid option as post-remission therapy for ALL patients in CR1 lacking a matched donor, we designed a disease-specific, prospective, multi-centre study. Patients Between July 2010 and Dec 2013, 186 patients with Philadelphia-negative high-risk ALL were biologically randomized to undergo un-manipulated HIDs (103 patients) or ISDs HSCT (83 patients) according to donor availability. Results Among HIDs and ISDs recipients, the 3-year disease free survival (DFS) rate was 68% and 64% (P =.56), respectively; overall survival (OS) rate was 75% and 69% (P = .51, respectively; cumulative incidences of relapse were 18% and 24% (P = .30), and those of the non-relapse-mortality (NRM) were 13% and 11% (P = .84), respectively. The 28-d myeloid recovery rates were both 99% in each group; the incidences of severe acute graft-versus-host-disease (GVHD) and chronic GVHD were also comparable between the two groups. Among recipients of transplantations from HIDs, no significant differences in DFS, OS, or NRM were observed between 3/6 and 4-5/6 matched grafts; in contrast, maternal donor was related with lower OS compared with other donor sources (P = .04); limited chronic GVHD was associated with better DFS (P = .01). The stem cell source had no effect on DFS. Conclusion Un-manipulated haploidentical-HSCT achieves outcomes similar to those of ISD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation was proved to be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor. (Chictr.org.cn number ChiCTR-OCH-10000940) Table. Results of multivariate analysis of outcomes Outcome Hazard ratio (95%Confidence interval) p value Disease free survival Haploidentical vs Identical sibling 0.88 (0.50-1.53) .65 Patient age <30 vs >30 years 0.74 (0.42-1.28) .28 Patient sex male vs female 1.13 (0.55-2.30) .74 Time to transplant <6 vs >6 months 1.48 (0.86-2.56) .16 Female-to-male vs other sex pair 0.95(0.52-1.75) .86 Limited chronic GVHD vs no or extended 0.59 (0.29-1.17) .13 Overall survival Haploidentical vs Identical sibling 0.91 (0.50-1.70) .77 Patient age <30 vs >30 years 0.60 (0.33-1.11) .11 Patient sex male vs female 1.13 (0.55-2.30) .74 Time to transplant <6 vs >6 months 1.64 (0.89-3.01) .11 Female-to-male vs other sex pair 1.22 (0.64-2.31) .54 Limited chronic GVHD vs no or extended 0.59 (0.27-1.28) .18 Relapse Haploidentical vs Identical sibling 0.67(0.33-1.36) .27 Patient age <30 vs >30 years 1.06 (0.50-2.28) .87 Patient sex male vs female 1.52 (0.64-3.62) .35 Time to transplant <6 vs >6 months 1.42 (0.69-2.90) .33 Female-to-male vs other sex pair 0.61(0.26-1.45) .27 Limited chronic GVHD vs no or extended 0.65 (0.26-1.62) .36 Non-Relapse-Mortality Haploidentical vs Identical sibling 1.38(0.58-3.35) .46 Patient age <30 vs >30 years 0.47 (0.19-1.17) .11 Patient sex male vs female 0.66 (0.19-2.33) .52 Time to transplant <6 vs >6 months 1.66 (0.70-3.92) .25 Female-to-male vs other sex pair 1.53(0.64-3.69) .34 Limited chronic GVHD vs no or extended 0.63 (0.21-1.86) .40 Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Keratinocyte Growth Factor Factor (Palifermin) in Combination with Tacrolimus and Methotrexate for the Prevention of Acute Graft-Vs-Host Disease (aGVHD) in Patients at High Risk of Agvhd.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1228-1228 ◽  
Author(s):  
Christopher M. Reynolds ◽  
John E. Levine ◽  
Joseph P. Uberti ◽  
Voravit Ratanatharathorn ◽  
Lois J. Ayash ◽  
...  
Keyword(s):  
High Risk ◽  
Keratinocyte Growth Factor ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Free Survival ◽  
Nonhematologic Toxicity ◽  
Graft Vs Host Disease ◽  
Continual Reassessment ◽  
Grade 3

Abstract In murine BMT systems, the administration of palifermin reduces small bowel damage and serum systemic inflammatory mediators resulting in less clinical aGVHD while preserving graft-vs-leukemia and improving leukemia free survival. We initiated a phase I schedule escalation trial of palifermin plus standard aGVHD prophylaxis (tacrolimus and 5 mg/m2 methotrexate on days 1, 3, 6, and 11) in patients with an unrelated or HLA mismatched donor who are at high risk for developing aGVHD. All study patients (n=35) had high risk hematologic malignancies and received a fully myeloablative conditioning regimen. Palifermin (60 mcg/kg/day intravenously) was administered for 3 consecutive days prior to the conditioning regimen, and then for 3 consecutive days each week starting Day 0, escalating by 6 doses per cohort, to a maximum of 36 doses. There were 6 cohorts, and each cohort had at least 2 patients. Dose schedules were escalated to the next cohort as long as the dose limiting toxicity (DLT) rate for the current cohort was less than 20% as determined by statistical analysis using a modified form of the continual reassessment method. A DLT was defined as any grade 3 or 4 nonhematologic toxicity that was possibly, probably, or definitely related to palifermin occurring within 14 days of receiving the final dose of palifermin. Nine DLTs were observed (table), and all patients were fully evaluable for aGVHD. In 20 patients, palifermin was not administered through engraftment—three patients completed palifermin prior to engraftment by protocol design (early cohorts), eight patients were removed from study due to DLTs, and nine patients discontinued palifermin by preference of either patient or physician. In this group of 20, 7 (35%) developed grade 3–4 aGVHD. In the other group of 15 patients, palifermin was administered through the time of neutrophil engraftment and only 3 (20%) developed grade 3–4 aGVHD. Mortality at 100 days for subjects who did not receive palifermin through engraftment was 30±10% compared to14±9% for patients who received palifermin through engraftment (p=NS). When adjusted for the interaction of palifermin administration with the number of methotrexate doses given (1–2 vs. 3–4), administration of palifermin through the time of engraftment was associated with improved survival (p = 0.02). Disease status at time of transplant (advanced vs non-advanced) and degree of HLA disparity (5/6 vs 6/6) did not alter the association. These preliminary data suggest that the administration of palifermin through the time of engraftment possibly has a survival benefit in patients at high risk for acute GVHD, perhaps mediated through an interaction with methotrexate. Dose Limiting Toxicities Toxicity # of patients # of palifermin doses Rash (gd 3) 4 2, 6, 6, 6 Hand-foot reaction (gd 3) 2 7, 9 Elevated amylase (gd 4) 1 3 Dyspnea (gd 3) 1 15 Hypoxia (gd 3) 1 15

Appropriate Patient Selection Before Allogenic Stem Cell Transplantation (allo-SCT) and Chronic GvHD After Allo-SCT Would Be Necessary for Better Outcome of Chemorefractory Non-Hodgkin's Lymphomas-A Single Institute Retrospective Study-.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4302-4302
Author(s):  
Nobuaki Nakano ◽  
Yosifusa Takatsuka ◽  
Shogo Takeuchi ◽  
Masahito Tokunaga ◽  
Mayumi Tokunaga ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Survival Time ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Disease Status ◽  
Allogenic Stem Cell Transplantation ◽  
Free Survival ◽  
Hodgkin's Lymphomas ◽  
Disease Free

Abstract Abstract 4302 Introductions Allogenic stem cell transplantaion (allo-SCT) for non-Hodgkin's lymphomas (NHLs) may be curative for chemorefractory patients, but few studies are available to guide transplant decision making in this setting. It would be very important to assess the eligibilities of allo-SCT for NHLs. To clarify the possibilities and eligibilities of allo-SCT for aggressive NHLs and come out the better prognostic factors, we analyzed 18 NHL patients who underwent allo-SCT in our institute retrospectively. Design and methods There were 55 NHL patients who had been undergone allo-SCT in our institute from August 2001 to March 2009. Thirty-seven patients out of 55 were adult T-cell leukemia/lymphoma (ATLL) patients, and we excluded these 37 ATLL patients in this study so that eliminate selection bias. We analyzed about rest of 18 patents. We analyzed 3 years overall survival (OS), disease free survival (DFS), related factors such as gender, age, diagnosis, disease status, IPI, HCT-CI score, transplantation methods, acute GVHD, chronic GVHD, and causes of death. Results Median age was 37.5 years old (19-63). Thirteen patients were male and 5 female. Diagnosis included FL (n=4), PTCL-u (n=3), MNKL (n=3), BL (n=2), DLBCL (n=2), ALCL (n=1), T-LBL (n=1), hepatosplenic lymphoma (n=1), and MF (n=1). Median overall survival time and disease free survival time after SCT were 215.5 days (6-2436) and 73 days (2-2436). Overall survival rate after SCT was 38.9%. IPI was Low in 2 patients, 8 L-I, 5 H-I, and 3 High. Low/L-I group showed significantly superior OS, DFS compare to H-I/High group (54% vs 0% p=0.0014, 56.3% vs 0% p=0.0112). HCT-CI scoring 0 in 12 patients, five 1, and only one patient scored over 2. HCT-CI score significantly related to OS after SCT in our cases (p=0.024). There were 13 sibling donors (included 5 HLA haplo-identical donors) and 5 unrelated donors (URD) (included 2 cord blood donors) in our cases. Ten patients received myeloablative conditioning and 8 reduced intensity conditioning (RIC). Disease status at SCT was CR in 5 patients, 7 PR, and 6 PD. Eleven patients died after SCT (3 a-GVHD, 2 disease progression, 2 sepsis, 1 TMA, 1 pneumonia, 1 invasive aspergillosis, and 1 liver failure). Five patients died within 100 days after SCT (three patients died within day 30). Six patients have been alive over 3 years (3 yrs OS, DFS: 33.3%, 27.8%). Seven patients were complicated grade 0-1 a-GVHD and 9 grade 2-4. Grade 0-1 group patients showed significantly superior DFS compare to grade 2-4 (p=0.0314). Five patients complained limited c-GVHD and 3 extensive. The patients group complained with c-GVHD showed better OS and DFS than asymptomatic group (53.6% vs 12.0% p=0.0062, 58.3% vs 12.5% p=0.0267). Four patients suffered relapse or progressive disease after SCT. Two out of these 4 patients showed GVL effect only with reducing immunosuppressive therapies. Discussion and conclusion Interestingly, about a-GVHD, grade 2-4 group obtained poor prognostic result compared to grade 0-1 group. On the other hand, the group which showed c-GVHD obtained better survival results. Our study was based on relatively small numbers of cases, but it might be showed that c-GVHD is important and GVL effect would be possibly existed. 3 years OS and DFS of allo-SCT for chemorefractory NHL in our institute were 33.3%, 27.8%, and NRM was 50%. Although it was not acceptable results, in some groups such as IPI Low/L-I, low scored HCT-CI groups, allo-SCT would be acceptable. Further studies including large patients numbers will be required. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Busulfan (Bu) and Cyclophosphamide (Cy) Based Conditioning Regimen Still Holds the Promise of Being a Safe and Efficacious Regimen for Allogeneic Transplantation in Patients with Transfusion Dependent Thalassemia (TDT) Even in High Risk

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 949-949
Author(s):  
Pallavi Mehta ◽  
Aakanksha A Singh ◽  
Neha Yadav ◽  
Narendra Agrawal ◽  
Rayaz Ahmed ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Mixed Chimerism ◽  
Class Iii ◽  
Free Survival ◽  
Grade 3

Abstract Introduction: Allogeneic stem cell transplantation (HSCT) is a potential curative treatment for TDT. BuCy based regimen has been used widely as a standard myeloablative chemotherapy. However, the use of treosulfan based conditioning regimen has increased over the last decade (Choudhary D et al BBMT 2013). We analysed the safety and efficacy of BuCy based vs Treosulfan/Thiotepa/Fludrabine (Treo/Thio/Flu) regimens in TDT between September 2013 and March 2021. Method: This is an observational retrospective hospital record-based study approved by Institutional Review Board. Regimen used: Treo/Thio/ Flu : Thiotepa 8 mg/kg , treosulfan 14 g/m2/day for 3 days, and fludarabine 40 mg/m2/day for 4 days . Flu/Bu/Cy/ATG : Fludrabine 30mg/ m2/ day for 6 days ,Antithymocytoglobulin 4.5mg/kg in 3 days , Busulfan (per oral) 14mg/kg ( boys) and 12mg/kg (girls) in 4 days, Cyclophosphamide 40mg/kg/day ( boys)and 50mg/kg/day ( girls) for 4 days. Statistical Analysis: Fisher's exact test was used for discrete variables and t-test was used for continuous variables. Log-rank test was used for the difference in survival between the groups. P value &lt; .05 was considered statistically significant. Cox regression for survival analysis was also used for time to event data of the predicted variables. Results: As shown in Table 1, 74 patients were enrolled, out of which 35 (47.2%) patients received BuCy based regimen whereas 39(52.7%) patients received Treo/Thio/Flu. All were fully HLA matched. Median age was 5.5 (1-12) years and 9 (1-15) years respectively. According to Lucarelli classification, number of patients with Class I, II, III were 17, 12, 6 in BuCy group vs 2, 14,18 in Treo/Thio/Flu group respectively. When stratified according to Matthew classification, 06 (17.1%) and 11 (28.2%) patients were in class IIIB respectively (Mathews V et al, BBMT 2007). Source of graft was bone marrow in BuCy group vs peripheral blood stem cell (PBSC) in Treo/Thio/Flu group. Mean CD34 cell dose was 3.82(2.2-9.1) vs 5(1.65-8.01) 106/kg in BuCy vs Treo/ Thio/Flu group respectively. Neutrophils and platelets engrafted at median of 16 days (14-21) and 16 days (9-47 ) in BuCy and 15 days (10-20) and 13 days (9-41) in Treo/ Thio/ Flu. Median duration of follow-up was 28 (23-32.9) months. Two (5.7%) patients had rejection (primary=1, secondary=1) in BuCy group whereas none in Treo/Thio/Flu. Five (14.3%) vs 10 (25.6%) patients developed grade ¾ oral mucositis respectively where 1 patient in each group belonged to Class III. Sinusoidal obstruction Syndrome (SOS) was observed in 02 (5.7%) vs 04 (10.3%) patients (p=0.047) respectively, with no patients affected in Class III. BuCy group had 04(11.4%) patients with acute GVHD, including one patient with grade 3. Treo/Thio/Flu group had 15(38.5%) patients with acute GVHD including 4 patients with grade 3 which had significant impact on survival (p=0.038). We also observed chronic GVHD in 04(11.4%) and 11(28.2%) patients respectively which was mainly limited stage in former and extensive in later which impacted the survival (p=0.031). CMV viremia was observed in 14 (40%) vs 8 (20.5%) patients respectively. We also encountered significant infections in both groups {21 (60%) vs 17 (43.6%)}, however, difference was not statistically significant. Four (5.1%) patients had transplant related mortality (TRM) in Treo/Thio/Flu group, in contrast to none in BuCy group. Commonest cause of death was sepsis. Mixed chimerism was commonly seen in BuCy group {20 (57.1%)} vs Treo/Thio/Flu group {12(30.1%)}.(Table 2) At last follow up, all alive patients except two patients with rejection are transfusion independent. Five-year Thalassemia-free survival (TFS) and overall survival (OS) of entire cohort was 94%+3% and 93%+4% respectively. Estimated OS and Event free survival (EFS) of BuCy vs Treo/Thio/ Flu was 100% vs 89.7% (p=0.060) and 93.9% vs 89.7% (p=0.472) respectively.(Figure 1) Discussion: We observed significant difference in TRM, acute and chronic GvHD and SOS favoring the BuCy group even in class III. On the contrary, we encountered rejections(n=2) and increased number of mixed chimerism in BuCy group which corroborates with previous literature (Fouzia N et al, BMT 2018). Conclusion: In our experience BuCy based conditioning regimen is a safe and effective regimen even in high risk class III TDT, with less TRM in comparison to Thio/Treo/Flu regimen. However, one needs to be vigilant for rejections and mixed chimerism. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning (RIC) Regimen Has the Capacity To Produce Durable Remissions and Long Term Disease-Free Survival in Patients with High Risk Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1141-1141
Author(s):  
S. Tauro ◽  
S. Mackinnon ◽  
K. Peggs ◽  
G. Begum ◽  
P. Mahendra ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract The toxicity of allogeneic stem cell transplantation (SCT) can be substantially reduced by the use of a reduced intensity conditioning (RIC) regimen and this has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with AML and MDS has not yet been defined and consequently their role in the management of these diseases remains conjectural. Seventy-six patients with high risk AML or MDS were allografted using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range 18–71 years). There were 46 males and 30 females; 41 patients received an allograft from an unrelated donor and 35 from a matched sibling donor. The 100 day transplant related mortality was 9% and no patient developed greater than Grade 2 graft-versus-host disease (GVHD). With a median follow-up of 36 months (range 13–70 months) 27 patients were alive and in remission with a 3y actuarial overall survival (OS) and disease-free survival (DFS) rate of 41% and 37% respectively. The 3y OS and DFS of patients with AML in complete remission (CR) at the time of transplantation was 48% and 42% respectively. In a multivariate setting, Cox regression analysis demonstrated prognostic significance of disease stage at the time of transplant with improved DFS in patients with AML in CR at the time of transplantation (HR=2.03, 95% CI=1.02–4.07). Disease relapse was the commonest cause of treatment failure occurring at a median time of 6 months post-transplant. Fourteen out of 27 (52%) patients relapsed within 6 months and 23/27 (85%) within twelve months defining a relatively narrow window for therapeutic intervention to prevent disease recurrence. The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts are capable of producing sustained disease free survival in a significant number of patients with AML who would be ineligible for allogeneic transplantation using a myeloablative conditioning regimen.

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