scholarly journals T- Cell Depleted Peripheral Blood Stem Cell (TCD-PBSC) Transplants Secure Consistent Engraftment with Low Risk of Acute or Chronic Gvhd and Favorable Disease Free Survival (DFS) and Overall Survival (OS) for Pediatric Patients (<21 years) with AML in CR1

2016 ◽  
Vol 22 (3) ◽  
pp. S251-S252
Author(s):  
Nancy A. Kernan ◽  
Farid Boulad ◽  
Susan E. Prockop ◽  
Andromachi Scaradavou ◽  
Rachel Kobos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Pediatric Patients ◽  
Peripheral Blood Stem Cell ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Primary Refractory Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4411-4411
Author(s):  
Sarita Rani Jaiswal ◽  
Sumita Chatterjee ◽  
Aditi Chakrabarti ◽  
Sneh Bhargava ◽  
Ray Kunal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Disease Status ◽  
Blood Stem Cell ◽  
Post Transplantation ◽  
Free Survival

Abstract In a pilot study, 75 patients with Primary Refractory (PRef) AML without matched family donors were offered post-transplantation cyclophosphamide (PTCY) based haploidentical peripheral blood stem cell (PBSC) transplantation. Twenty-seven patients (36%) opted for haploidentical transplantation with or without further chemotherapy. There was no difference in the patient or disease characteristics amongst patients undergoing transplantation or not. The conditioning regimen comprised of FluCyMel (n=5), FluBuMel (n=17) and FluTreoTBI (n=5). MMF was tapered between days 14 and 21 posttransplant in the absence of GVHD and cyclosporine A was tapered between days 60 and 90. The progression free survival at a median follow-up of 25 months was 36.6% and 0% in the transplant and the non-transplant group (p=0.0001). Prompt engraftment was noted at a median of 14 days irrespective of disease status or conditioning regimens. Cumulative incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were 26.6% and 8% respectively. The overall incidence of infections remained low, with CMV reactivation and invasive aspergillosis occurring in 9 and 2 patients respectively. CMV disease was diagnosed in 2 patients. Non-relapse mortality at 1 year was 16.7%. The incidence of disease progression was 54%. Factors positively impacting progression free survival were < 15% marrow blasts at transplant and a Natural Killer Cell Ligand Mismatch (NKLMM) donor. NKLMM, Haplotype or B scores had no impact on CMV infection or GVHD. However, Bx Haplotype was associated with lower NRM (5%, 95%CI-1-9) compared to 48.6% (95%CI 28.2-69.0) in AA Haplotype (p=0.01). Disease status did not impact the overall survival (p=0.11) in the HSCT cohort. In fact, NKLMM donors with B haplotype had the greatest impact on overall survival in both the HSCT cohort (71.4%, 95%CI 54.3-88.5%) compared to 20% (95%CI 8.8-31.2, p=0.01) in those without the same. Our data suggests PTCY based Haploidentical PBSC transplantation is feasible in patients with PRef AML and donor NKLMM might improve progression free survival, provided the conditioning protocol and the post-grafting therapy offer the optimum platform for alloreactivity of NK cells. Disclosures No relevant conflicts of interest to declare.

Analysis of 120 Pediatric Patients with Non-Malignant Disorders Transplanted Using Unrelated Plasma Depleted Cord Blood and the Role of Post-Thaw Wash

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4406-4406
Author(s):  
Joseph Rosenthal ◽  
Tang-Her Jaing ◽  
Lee Lee Chan ◽  
Gretchen Eames ◽  
Michael L. Graham ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Pediatric Patients ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Related Mortality

Abstract Unrelated cord blood (UCB) is an important stem cell source for unrelated hematopoietic cell transplantation of patients with non-malignant disorders. Cell dosage is a critical factor for successful UCB hematopoietic stem cell transplantation (HSCT). The red cell reduced (RCR) and post-thaw wash techniques that are widely used incur significant nucleated cell loss. Three strategies were employed to maximize cell dose and improve outcome–use of cord blood processed with plasma depletion without red blood cell reduction (PD CB), avoidance of post-thaw wash, and the use of double cords (2X) when necessary. A CIBMTR-audited analysis was performed on all 120 pediatric patients with non-malignant disorders transplanted with PD CB at 29 U.S. and 17 international centers. Transplant characteristics: median age 3.5 years (range 0.1–14); median patient weight 15 kg (range 4–61); male 58%. The majority of patients (n=58; 55%) were Asian. Twenty-two (21%) patients were Hispanic, 15 (14%) were Caucasian, 6 (6%) were African-American, and three (3%) were of Middle Eastern background. HLA ABDR matches: 6/6–26; 5/6–48; 4/6–47; 3/6 or 2/6–6; median pre-freeze nucleated cell dose 10.5×107/kg; median pre-freeze CD34+ dose 3.7×105/kg; non-myeloablative regimen 24%; 58% infused without post-thaw wash (NW). Myeloid engraftment defined as ANC≥500 and 6-month platelet engraftment defined as ≥ 20K and ≥ 50K are 89±8%, 88±8%, and 84±6% respectively. The median time to myeloid and platelet engraftment are 21 days (range 11–64), 49 days (range 13–155), and 61.5 days (range 21–205) respectively. No major adverse event was observed in either the W or the NW group. The cumulative incidence of reported grade II–IV acute GVHD was 38±5%, and 19±4% had grade III–IV acute GVHD. 36±6% developed limited chronic GVHD, and 12±4% developed extensive chronic GVHD. With a median follow-up of 329 days (range 3–1928 days), the Kaplan-Meier estimates of 1-year TRM, OS and diseasefree survival were 20±6%, 88±6% and 72±6% respectively. Foregoing post-thaw wash for PD CB transplantation improved neutrophil (RR=1.75; p=0.01) and platelet engraftment (RR=1.72; p=0.02) and reduced TRM (RR=0.38; p=0.04). This series demonstrated that unrelated PD CB transplantation can be performed safely and effectively in children with life-threatening, non-malignant disorders. Additionally, the results demonstrate possible improvement in myeloid and platelet engraftment, overall and disease-free survival when post-thaw wash is not employed. Table 1. Summary of overall results Outcome All Patients N = 120 Washed CB N = 48 Unwashed CB N = 71 RR (Wash=Ref) P-value ANC500 Engraftment Cumulative Incidence Median # Days to Engraftment 87±6% d+21 86±9% d+25 89±8% d+19 1.75 0.01 Platelet 20K Engraftment Cumulative Incidence Median # Days to Engraftment 81±6% d+49 75±9% d+52 88±9% d+43 1.72 0.02 Autologous Recovery 3±2% 2±2% 4±3% 1.06 0.95 Acute GvHD II–IV Acute GvHD III–IV 38±5% 19±4% 31±7% 17±6% 45±7% 21±6% 1.74 1.38 0.11 0.50 Chronic GvHD Limited Chronic GvHD Extensive 36±6% 12±4% 14±6% 19±6% 60±10% 6±4% 5.69 0.24 &lt;0.001 0.08 Transplant-Related Mortality–100 Day Transplant-Related Mortality–3 Yr 10±3% 20±4% 11±5% 34±8% 9±4% 11±4% 0.38 0.04 Overall Survival–1 Yr Overall Survival–3 Yr 79±4% 79±4% 66±8% 66±8% 88±4% 88±4% 0.43 0.06 Disease-Free Survival–1 Yr Disease-Free Survival–3 Yr 72±5% 70±6% 58±9% 51±10% 84±5% 84±5% 0.48 0.07

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.

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.

Improved Outcomes for Peripheral Blood Stem Cell Transplantation in Advanced Myelodysplastic Syndrome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2304-2304
Author(s):  
Scott R. Solomon ◽  
Richard Childs ◽  
Aldemar Montero ◽  
Elaine Sloand ◽  
Laura Wisch ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
Advanced Disease ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Blood Stem Cell Transplantation ◽  
Reduced Intensity ◽  
Risk Of Relapse ◽  
Related Mortality

Abstract Allogeneic marrow or peripheral blood stem cell transplantation (PBSCT) is the only curative treatment for myelodysplastic syndrome (MDS). Historically, transplantation for MDS has produced long-term disease-free survival rates of 30–40%, partially due to high procedural mortality (~40%) in this patient population. Although transplant outcomes in younger patients with low-risk disease have been favorable, inferior results are seen in older patients and those with more advanced disease. Evidence suggests that the lower transplant-related mortality (TRM) and improved graft-versus-leukemia seen with PBSCT may translate into improved clinical outcomes for MDS patients. Forty-four patients, aged 12–73 years (median 50) received a PBSCT from a matched related sibling donor (MRD). Patients aged <55 years, without prohibitive comorbidity, received myeloablative conditioning consisting of total body irradiation and cyclophosphamide, followed by a T cell depleted allograft and scheduled post-transplant donor lymphocyte infusions (MST, n=23). Patients ineligible for an ablative transplant due to age or poor health received reduced intensity conditioning (fludarabine and cyclophosphamide, melphalan, or busulfan) followed by a T cell replete allograft (n=21). Six patients had low-risk MDS (RA/RARS), while the majority of patients (86%) had advanced disease (RAEB [9], RAEBT [6], AML [13], therapy-related MDS [10]). Median follow-up is 15.3 (range 2–82) months. Patients with therapy-related MDS had a significantly lower survival rate due to a very high risk of relapse (figure). The actuarial probabilities of overall survival (OS), disease-free survival (DFS), relapse, and TRM were 64%, 59%, 26%, and 23% for primary MDS patients, and 51%, 47%, 40%, and 25% for the whole cohort. Transplant-related mortality in patients under 50 years of age was 11% vs. 45% in patients ≥50 years (p=0.03). OS and DFS were significantly better in recipients of MST (64%, 57%) than in patients receiving reduced-intensity PBSCT (33%, 34%), due to a higher risk of relapse in the latter group (55% vs. 29%, p=0.10). In nineteen patients <50 years receiving MST, actuarial probability of OS, DFS, relapse, and TRM were 81%, 72%, 23%, and 7%, respectively. In summary, PBSCT yields superior outcomes for patients with primary MDS, even in patients in transformation to AML. The inferior outcomes seen in therapy-related MDS suggest alternative therapies are required for this patient population. Reduced intensity transplantation permits curative therapy for MDS patients not amenable to MST, but at the price of increased TRM and relapse in this older cohort. Figure Figure

Induction of Remission Prior to Transplantation Improves the Disease-Free Survival (DFS) of Patients with Advanced Myelodysplastic Syndromes (MDS) Treated with Myeloablative T-Cell Depleted (TCD) Stem Cell Transplants (SCT) from HLA Identical Siblings.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5426-5426
Author(s):  
H.R. Castro-Malaspina ◽  
Ann A. Jakubowski ◽  
Esperanza B. Papadopoulos ◽  
Farid Boulad ◽  
James W. Young ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Marrow Cell ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Untreated Group ◽  
Refractory Anemia ◽  
Marrow Graft ◽  
Failure Group

Abstract Posttransplant relapse is a major limitation to the success of allogeneic SCT in patients with advanced MDS (refractory anemia with excess blasts (RAEB I and II), refractory anemia in transformation (RAEB-t), and acute myeloid leukemia transformed from MDS). The use of induction chemotherapy prior to transplant to induce remission and thereby to reduce posttransplant relapse in these patients remains controversial. From 1985 to 2004, 47 patients with advanced MDS underwent bone marrow or peripheral blood SCT from HLA identical siblings after myeloablative conditioning with total body irradiation (TBI) and cyclophosphamide alone or in some combined with thiotepa, carboplatinum, diaziquone, or etoposide, or TBI combined with thiotepa and fludarabine. Thirty-six patients received low dose (3 patients) or full induction (33 patients) chemotherapy before conditioning, and 11 patients did not receive any chemotherapy. Prior to transplant, 22 of the 36 treated patients were in hematologic remission (CR) and 4 achieved a second refractory cytopenia phase (RCy2) for a total of 26 responders, and 10 had failed to respond to chemotherapy. Marrow grafts were depleted of T cells using soybean lectin agglutination and then sheep RBC-rosetting (n=32 patients). G-CSF-mobilized peripheral blood stem cell (PBSC) grafts underwent positive CD34 selection and T-cell depletion by sheep RBC-rosetting (n=10 patients). Five patients received a marrow graft followed by a PBSC allograft from the same donor because of low marrow cell dose. Rejection prophylaxis with anti-thymocyte globulin was used in 33 patients. No posttransplant pharmacologic prophylaxis for GvHD was given. The median age was 48 years (range 13–61). Forty-three of the 47 patients in this series engrafted, and 2 had primary graft failure. Two patients died before engraftment. Only 3 patients developed acute GvHD (grades 1 and 3) and 1 chronic GvHD. At 5 years posttransplant, the DFS was 44% for the patients in CR and RCy2 at time of transplant, but no patients in the untreated group or in the chemotherapy failure group survived (p=0.0004). The cumulative incidence (CI) of relapse at 2-years posttransplant for the responders was 27.0%, for the failures 50%, and for the untreated group 45%. The CI for non-relapse mortality at 2-years posttransplant was 19% for the responders, 40% for the failures, and 36% for the untreated patients. All survivors have achieved ≥KPS 90%. These results indicate that patients with advanced MDS who achieve remission or a second refractory anemia phase with chemotherapy before TCD allogeneic SCT can achieve successful long-term remisions. In contrast, the high incidence of posttransplant relapse mitigates against the use of TCD SCT in patients with advanced MDS with active disease (≥5% blasts) prior to transplant. Prospective multicenter randomized studies are needed to validate the value of pre-transplant chemotherapy in patients with advanced MDS undergoing allogeneic SCT.

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