Post-That Washing Prior to Transplantation of Umbilical Cord Blood (UCB) That Were Depleted of Plasma but Not of Red Blood Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5229-5229
Author(s):  
Robert Chow ◽  
Patrick Tan ◽  
Tang-Her Jaing ◽  
Joseph Rosenthal ◽  
Auayporn Nademanee ◽  
...  
Keyword(s):  
Median Time ◽  
Relapse Rate ◽  
Survival Data ◽  
Negative Impact ◽  
Chronic Gvhd ◽  
Cell Recovery ◽  
Hematopoietic Stem ◽  
Kaplan Meier ◽  
M Estimate ◽  
M Estimates

Abstract Washing after thawing of frozen UCB used for hematopoietic stem cell transplantation (HSCT) is widely practiced for the purpose of removal of the cryoprotectant DMSO and free hemoglobin from lysed red cells. An updated retrospective audited analysis was performed on the outcomes of 208 PD UCB used in 186 patients with known thaw conditions that have engraftment and/or survival data −106 washed (W) and 80 non-washed (NW). When the DMSO dose was kept under the recommended 1 g per kg of recipient weight, the only severe adverse reaction was a seizure and encephalopathy following infusion of a NW PD UCB that resolved without any sequelae. Total nucleated cell recovery after thawing as reported by transplant centers was higher for NW (median 89% vs. 75%). The Kaplan-Meier estimate of 3-month neutrophil (ANC500) engraftment were 91±4% for NW versus 88±4% for W with median time to neutrophil of 21 versus 24 days (p = 0.02). The K-M estimate for 6-month platelet 20K engraftment were 86±6% for NW and 78±5% for W with median time to engraftment at 46 days for NW and 55 days for W (p = 0.002). Acute grade III–IV GvHD were similar at 12% (NW) and 13% (W), but extensive chronic GvHD were 4% (NW) and 19% (W). 1-year TRM were 25±5% for NW and 34±5% for W (p=0.75), with relapse rate at 16±5% for NW and 28±5% for W (p=0.09). K-M estimates of 1-year OS were 63±6% versus 53±5% (p = 0.54), and for 1-year DFS were 62±6% versus 48±5% (p = 0.23) for NW and W respectively. To our knowledge, this was the largest transplant outcome study comparing no post-thaw wash versus wash for UCB, though the conclusions are confined to PD CBU. No clear benefits of post-thaw washing were seen for PD UCB. HSCT with NW PD UCB was at least as efficacious as that using W PD UCB with respect to GvHD, TRM, relapse rate, 1-year OS and DFS. Moreover, washing may have a negative impact on neutrophil and platelet engraftment of PD UCB.

Effect of Post-Thaw Washing Prior to Transplantation of Umbilical Cord Blood Units (UCB) That Were Depleted of Plasma but Not of Red Blood Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5283-5283
Author(s):  
Robert Chow ◽  
David Gjertson ◽  
Joseph Rosenthal ◽  
Auayporn Nademanee ◽  
Chatchada Karanes ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Relapse Rate ◽  
Blood Cells ◽  
Negative Impact ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Hemoglobin ◽  
Hematopoietic Stem ◽  
Similar Clinical Outcome ◽  
Neutrophil Engraftment

Abstract Background: Washing after thawing of frozen UCB used for hematopoietic stem cell transplantation (HSCT) is widely practiced for the purpose of removal of the cryoprotectant DMSO and free hemoglobin from lysed red cells; however, frozen peripheral blood stem cells with similar loads of free hemoglobin and DMSO are often thawed and infused directly without washing. Recently, similar clinical outcome and post-thaw viability were seen with the standard red cell depleted (RCD) UCB whether washing was employed after thawing or not. However, no data exist on the utility of post-thaw washing for UCB that were depleted of plasma (PD) but not depleted of red blood cells. Hypothesis: Myeloid and platelet engraftment, speed of engraftment, overall survival (OS), disease-free-survival (DFS), and transplant related mortality (TRM) will be similar in two comparable groups of patients who received frozen PD CBU that were washed (W) or not washed (NW) after thawing. Methods: A retrospective analysis was performed on the outcomes of 84 patients in remission without history of prior transplants, who received either washed (n=43) or non-washed (n=40) PD UCB units for HSCT. Results: Adverse events of any grade occurring more than once during infusion include hemoglobinuria (9NW, 1W), hypertension (6NW, 4W), hives (1NW, 1W), nausea/vomit (2NW) and dyspnea (1NW, 1W). One patient developed seizure and encephalopathy, although relationship to infusion was uncertain. Total nucleated cell recovery after thawing is higher for NW (median 95% vs. 75%). Unadjusted cumulative incidence (C.I.) of neutrophil engraftment was similar for both groups, 91±5% for NW (n=36) versus 93±4% for W (n=41), but median time to neutrophil (20 vs 26 days) and platelet engraftment (platelet 20K 47 vs. 55 days & platelet 50K 55 vs 63 days) occurred earlier for NW. Additionally, C.I. for platelet 20K engraftment was higher for NW (n=28; 92±6%) than W (n=39; 75±7%). Acute grade III–IV GVHD were 10% (NW) and 19% (W), and extensive chronic GVHD were 0% (NW) and 22% (W). TRM was 18±6% for NW and 20±7% for W, with the relapse rate for malignant cases at 11±7% for NW and 25±8% for W. One-year OS was 75±7% (n=40) versus 72±8% (n=43), and 1-year DFS was 69±10% (n=23) versus 54±9% (n=34) for NW and W respectively. Conclusion: No clear benefits of post-thaw washing for PD UCB prior to HSCT was found, except for the anticipated lower incidence of transient hemoglobinuria. HSCT with NW PD CBU was at least as efficacious as that using W PD units with respect to neutrophil engraftment, TRM, relapse rate, 1-year OS and DFS. Moreover, washing may have a negative impact on C.I. of platelet engraftment and the speed of neutrophil and platelet engraftment. The questions of PD versus RCD UCB and post-thaw W versus NW have important clinical consequences and prospective randomized studies are needed to clarify these issues.

Hematopoietic Stem Cell Transplantation (HSCT) for Benign Indications Using Plasma Depleted Umbilical Cord Blood Units (UCB) That Were Not Depleted of Red Blood Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3151-3151 ◽  
Author(s):  
Joseph Rosenthal ◽  
Tang-Her Jaing ◽  
Auayporn Nademanee ◽  
Chatchada Karanes ◽  
Michael Graham ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Median Time ◽  
Blood Cells ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Loss ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Kaplan Meier ◽  
Benign Disorders

Abstract UCB is an attractive source for unrelated HSCT of benign indications; however, cell dosage is a critical factor for UCB HSCT. The red cell depletion (RD) and post-thaw wash techniques that are widely used incur significant nucleated cell loss; therefore, two strategies to minimize cell loss are to deplete plasma, but not the red blood cells (PD) during processing and forego post-thaw wash. A retrospective audited analysis was performed on 61 patients with benign disorders who were transplanted with 68 PD UCB units (8 double cords) with 29 thalassemias, 8 AA, 5 WAS, 5 SCID, 2 osteoporosis, 2 sickle cell disease, 2 Hemophagocytic Lymphohistiocytosis, 2 Hurler Syndrome, 1 CGD, 1 Fanconi’s Anemia, 1 Leroy I-Cell Disease, 1 Lymphohistiocytosis, 1 OIMD, and 1 Alpha Mannosidosis. Transplant characteristics: patient median age 4.25 years old (range 0.3–39); median weight 17 kg (range 5–76); male 56%; median # HLA ABDR matches of 5.0 (12–6/6; 19–5/6; 23–4/6; 5–3/6, 1–2/6); median pre-freeze TNC dose 8.1 x 107/kg; median post-thaw TNC dose as reported by TC 7.7 x 107/kg; median pre-freeze CD34 dose 3.1 x 105/kg; transplants outside of U.S.− 32 (52%); non-myeloablative − 9; 44% post-thaw washed (W), 56% infused without post-thaw wash (NW). The Kaplan-Meier estimates of 3-month ANC500 and 6-month platelet 20K and 50K engraftment are 87±5%, 83±6%, and 84±6% respectively. The median time to engraftment for ANC 500, platelet 20K, and 50K are 20 days (range 11–64), 46 days (range 13–153), and 61 days (range 21–171) respectively. No major adverse event was observed in either the W or the NW group, and the median time to engraftment for ANC 500, platelet 20K and 50K for W vs. NW were 21 vs. 19 days, 55 vs. 44.5 days, and 76 vs. 59 days respectively. The incidence of reported grade II–IV acute GVHD was 29%, and 10% had grade III–IV acute GVHD. 33% developed limited chronic GVHD, and 15% developed extensive chronic GVHD. With a median follow-up of 219 days (range 4–1402 days), the Kaplan-Meier estimates of 1-year TRM, OS and disease-free survival were 20±6%, 78±6% and 72±6% respectively. These results demonstrate that HSCT using unrelated PD UCB can be performed safely with outstanding results in patients with benign disorders, and post-thaw washing may delay engraftment of HSCT using PD UCB.

Hematopoietic Stem Cell Transplantation (HSCT) for Malignancies Using Plasma Depleted Umbilical Cord Blood (UCB) That Were Not Red Blood Cell Depleted.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5418-5418
Author(s):  
Lawrence Petz ◽  
Auayporn Nademanee ◽  
Joseph Rosenthal ◽  
Michael Graham ◽  
Gretchen Eames ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Chronic Gvhd ◽  
Cell Loss ◽  
Limiting Factor ◽  
Racially Diverse ◽  
Hematopoietic Stem ◽  
Kaplan Meier ◽  
Grade Ii ◽  
Available Information

Abstract Cell dosage is a limiting factor for UCB HSCT, especially for adult patients. Most UCB banks practice red cell depletion (RCD) techniques to save storage space, which incur significant nucleated cell loss after processing. One method to minimize cell loss and still reduce volume after processing is to deplete plasma (PD), but not the red blood cells. Not washing UCB (NW) after thawing also minimizes cell loss. A large racially diverse PD UCB inventory of over 25,000 units is now available on stem cell registries. There were 70 ALL, 54 AML, 19 CML, and 45 others transplanted for malignant indications. A retrospective audited analysis was performed on 170 patients with engraftment and/or survival information. Of the ALL/AML/CML cases with available information, there were 32 1CR/CP, 33 2CR, and 13 3CR/CP. The median age of patients was 13 years old (range 05–59); median weight 50 kg (range 5–137); male 45%. Transplant characteristics indicated a median # HLA ABDR matches of 4.0; median pre-freeze TNC dose 4.1 × 107/kg; median post-thaw TNC dose as reported by TC 3.7 × 107/kg; median pre-freeze CD34 dose 1.4 × 105/kg; transplants outside of U.S. 34%; double unit transplant 30%; non-myeloablative 16%. Sixty-one percent of the transplanted UCB were washed post-thaw (W), 39% were infused without post-thaw wash (NW), with 20% of the units without available post-thaw data. Kaplan-Meier estimates of 3-month ANC500 and 6-month platelet 20K and 50K engraftment are 89±3%, 81±5%, and 73±5% respectively. Median time to engraftment for ANC 500, platelet 20K, and 50K were 22 days (range 7–69 days), 52.5 days (range 12–181 days), and 64 days (range 25–374 days) respectively. Median time to engraftment for post-thaw washed units (W) versus PD CBU not washed and infused directly after thawing (NW) were 24 vs. 22 days for ANC500, and 57 vs. 48 days for platelet 20K respectively. The incidence of reported grade II-IV and III-IV acute GVHD were 32% and 14% respectively. Twelve percent developed limited chronic GVHD and 14% developed extensive chronic GVHD. With a median follow-up of 170 days (range 4–1402 days), the Kaplan-Meier estimates of 1-year TRM, OS and relapse-free survival were 31±4%, 51±4% and 47±4% respectively. These results demonstrate that HSCT using unrelated PD UCB can be performed safely and effectively in patients with malignancies, and post-thaw wash may not be necessary.

Hematopoietic Stem Cell Transplantation (HSCT) Using Plasma Depleted Umbilical Cord Blood (UCB) That Were Not Red Cell Depleted.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5231-5231
Author(s):  
Robert Chow ◽  
Patrick Tan ◽  
Tang-Her Jaing ◽  
Joseph Rosenthal ◽  
Auayporn Nademanee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Survival Data ◽  
Chronic Gvhd ◽  
Cell Loss ◽  
Red Cell ◽  
Racially Diverse ◽  
Hematopoietic Stem ◽  
Kaplan Meier ◽  
Transplant Center ◽  
One Year

Abstract UCB is an attractive source for HSCT; however, limiting cell dose has hampered its widespread use. The red cell depletion (RCD) techniques that are widely used incur significant nucleated cell loss after processing; therefore, to minimize cell loss and still reduce volume during processing, a technique was devised to deplete plasma (PD) but not red blood cells. A large racially diverse inventory of over 25,000 PD UCB is available on stem cell registries. Of the 265 PD UCB transplanted into 240 patients up to May 2006, an updated retrospective audited analysis of all 205 patients with engraftment and/or survival data was performed. The characteristics for the patients were: median age 8.8 yo, range 0.3–59, 76 ≥16 yo (32%); median weight 29 kg, range 5–137, 84 ≥50kg (35%); male 59%; median # HLA ABDR matches 4.0; median pre-freeze TNC dose 5.31 × 107/kg (n=229); transplant center reported median post-thaw TNC dose 4.92 × 107/kg (n=112); median pre-freeze CD34 dose 1.7 × 105/kg; malignant indications 71%; transplants outside U.S. 39%; double transplant 23%; and non-myeloablative 15%. For all engrafted patients, the median time to engraftment for ANC 500 (n=192), platelet 20K (n=174) and 50K (n=169) were 22.0 days (range 7–64), 49.5 days (range 12–181), and 63.5 days (range 21–374) respectively. Kaplan-Meier estimates of engraftment of ANC500, platelet 20K and 50K engraftment were 88±3%, 82±4% and 76±4% respectively. The incidence of grade III–IV acute GVHD and extensive chronic GVHD were 13% and 14% respectively. One-year relapse rate was 23±4% for all patients (n=190), and TRM was 29±3% (n=203) at 1 year. With a median follow-up of 178 days (range 4–1402 days) for the surviving patients, the Kaplan-Meier estimates of 1-year OS (n=203) and DFS (n=190) are 59±4% and 54±4% respectively for all patients. These results demonstrate that HSCT using PD UCB can be performed safely and effectively.

Impact of HLA Class I Typing-Resolution and Mismatches on Survival and Graft-Versus-Host Disease in Patients after Hematopoietic Stem Cell Transplantations from Unrelated Donors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2060-2060
Author(s):  
Miroslaw Markiewicz ◽  
Jerzy Wojnar ◽  
Malgorzata Krawczyk-Kulis ◽  
Iwona Wylezol ◽  
Sebastian Giebel ◽  
...  
Keyword(s):  
High Resolution ◽  
Relapse Rate ◽  
Graft Failure ◽  
Statistical Significance ◽  
Chronic Gvhd ◽  
Hla Class I ◽  
Class I ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Grade 3

Abstract We analyzed 150 consecutive patients (pts) transplanted from unrelated donors (URD) at single institution- Silesian Medical Academy in Katowice- with use of the same standard operating procedure from February 1997 until December 2004 for CML (74 pts), AML (28), ALL (27), SAA (9), MDS (7), MM (1), NHL (1), PNH (1), OMF (1), bi-phenotypic AL (1). 92 pts were transplanted from matched donors, including 59 with complete 10 alleles (HLA-A,B,C,DRB1,DQB1) high resolution (HR) DNA-typing; and 33 with first class match established on base of low-resolution (LR) (13), serological (7) or un-complete typing without HLA-C (13) and second class HR typing. 58 pts were transplanted from mismatched donors (first class typing was HR in 43, LR in 14 and serological in 1 pt): 22 with single allelic mismatch (2 HLA-A, 7-B, 6-C, 7-DQB1), 33 with single HLA-C antigen mismatch and 3 with double mismatches (2 B+C, 1 C+C). Survival advantage at 4 years, although without statistical significance (p=0.16), was observed in the group of pts transplanted from 10/10 alleles matched donors (36+/− 11%) over those with mismatched donors (24+/− 11%). Oppositely, pts transplanted from matched donors who were not completely typed in HR did not achieve better survival (23+/− 17%). Poorest survival (13+/− 12%, p=0.007) was observed in patients transplanted from mismatched homozygous donors (n=10). The risk of acute GVHD grade 3–4 was increased (p=0.007) in pts with mismatched donors (31+/− 6%) when compared to matched completely typed in HR (10+/− 4%). Also the rate of graft failure tended to be lower in pts with matched than mismatched donors (5.1% versus 10.2%, p=0.25). In contrast, relapse rate was lower in mismatched (23+/− 10%) than in HR matched pts (34+/− 12%, p=0.55) what may reflect better GVL effect in mismatched transplant recipients. Unexpectedly, the rate of chronic GVHD was similar in pts with 10/10 alleles matched and mismatched donors (40+/− 10% versus 42+/− 9%, p=0.75). These results indicate that complete high resolution HLA class I typing is necessary for adequate selection of unrelated donors. Class I HLA-B and -C mismatches influence both survival and serious a-GVHD incidence. 10/10 alleles matched mismatched p survival at 4 years 36+/− 11% 24+/− 11% 0.16 aGVHD grade 3–4 10+/− 4% 31+/− 6% 0.007 graft failure rate 5.1% 10.2% 0.25 relapse rate 34+/− 12% 23+/− 10% 0.55 cGVHD 40+/− 10% 42+/− 9% 0.75 10/10 alleles matched mismatched homozygous donors p survival at 4 years 36+/− 11% 13+/− 12% 0.007

Allogeneic Stem Cell Transplantation (Allo-SCT) in the Management of Advanced Waldenstrom’s Macroglobulinemia (WM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 619-619
Author(s):  
Charalampia Kyriakou ◽  
C. Canals ◽  
A. Sureda ◽  
G. Taghipour ◽  
J. Cornelissen ◽  
...  
Keyword(s):  
Median Time ◽  
Relapse Rate ◽  
Residual Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Mixed Chimerism ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Difference

Abstract Despite effectiveness of standard chemotherapy regimens, complete response is infrequent in WM patients and there is no cure. The role of Allo-SCT has not been extensively explored and the available data are limited. In this retrospective European multicenter study we report the outcome of 106 WM patients (69 male) who underwent an Allo-SCT between 1989 and 2005 and were reported to the EBMT Lymphoma Database. The median age at transplant was 49 years (21–65), and the median time from diagnosis to SCT was 34 months (5–310). The median number of treatment lines prior to allo-SCT was 3(1–10) and 19 patients had failed a prior autograft. Ten (10%) patients were in 1st maximum response (MR), 35 (33%) in PR1, 29 (27%) in PR≥2 and 32 (30%) had refractory disease at the time of transplantation. Forty-four patients were treated with conventional (CT) conditioning protocols; [Cy/TBI n=24, Melphalan/TBI, n=6, BuCy n=14] and 62 with a reduced intensity protocol (RIC); [Fludarabine based regimen n=43, Low dose TBI/Cy n=19] With a median follow up of 31 months (3 to 169) 59 (56%) patients, are alive and free of disease. Forty-eight (45%) patients developed aGVHD [Grades I-II (n=34), Grades III-IV (n=14)] with no statistically significant difference between conventional and RIC groups. Five out of nine RIC patients developed aGVHD following the administration of donor lymphocytes for either residual disease or mixed chimerism. Sixteen patients (15%) developed limited and 11 (10%) extensive chronic GVHD. Seventeen (16%) patients relapsed at a median time of 8 (1–89) months after allo-SCT. Thirty-five (33%) patients died, 5 (5%) from disease relapse or progression and 30 (28%) from regimen toxicity. Non-relapse mortality rates were estimated of 30% and 33%, at 1 and 3 years, respectively, for the CT group, and 24% and 30% for the RIC group of patients. Relapse rates at 1 and 3 years were 10%, 12% for the CT group and 14% and 25% for the RIC. Progression free survival (PFS) rates were 60%, 54% and 54% at 1, 3 and 5 years for the CT and 61%, 44% and 39% for the RIC patients. Overall survival was 65%, 59% and 59% for the CT and 71%, 66% and 66% for the RIC at 1, 3 and 5 years, respectively. Multivariate analysis showed that chemorefractory disease at allo-SCT was associated with a significantly higher relapse rate [p<0.03; 95% CI 1.1–8.9] while the use of TBI in the conditioning regimen with a significantly lower relapse rate [p<0.02; 95% CI 1.1–9.3]. There were no differences in outcome when considering the intensity of the conditioning regimen. In conclusion, allo-SCT is a feasible and well-tolerated procedure in this group of elderly patients with advanced disease. In addition, relapse rate after the allogeneic procedure is low resulting in a good long-term outcome.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia (AML) with Complex Karyotypes (CK): A Retrospective Study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) and MD Anderson Cancer Center (MDACC)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3479-3479
Author(s):  
Stefan O. Ciurea ◽  
Myriam Labopin ◽  
Emmanuelle Polge ◽  
Piyanuch Kongtim ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Relapse Rate ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Secondary Aml ◽  
Equity Ownership ◽  
Active Disease

Abstract Introduction CK AML patients have high relapse rate and poor outcomes when treated with conventional chemotherapy. Allogeneic hematopoietic stem cell transplantation (AHSCT) may cure this disease; however, relapse rate remains a major limitation and survival is one of the worst amongst AML patients. Here we aimed to identify prognostic factors associated with survival in patients with AML and CK using combined data from the EBMT and MDACC. Methods A total 1,342 consecutively transplanted patients with CK (>3 cytogenetic abnormalities) AML reported to EBMT (N=1,118) and at MDACC (N=224) between 01/2000-12/2015 were included.The median age was 52 years (range 18-76 years), 335 patients (25%) were older than 60 years. Seven hundred and twenty-nine patients (54.3%) were male, 239 patients (17.8%) had secondary AML. Disease status before transplant was CR1, CR2 and activediseasein 877 (65.3%), 77 (5.7%) and 388 (29%), respectively. Donors were matched related (MRD), matched unrelated (MUD) and mismatched unrelated (MMUD) in 749 (55.8%), 513 (38.2%) and 80 (6%), respectively. Conditioning regimens were various, mostly eitherbusulfan-based (53.7%) or TBI-based (26.7%). Seven hundred and thirty-nine patients (55%) and 603 patients (45%) receivedmyeloablativeconditioning (MAC) and reduced intensity conditioning (RIC), respectively. The main stem cell source was peripheral blood (81%). In vivo T-cell depleted (TCD) methods were used in 665 patients (50%). Median time from diagnosis to transplant was 5.1 months (range 2-387 months) while the median follow-up duration was 35.5 months (range 8-174 months). Results Engraftment occurred in 96.3%, 69.7% and 30.3% had full and mixed donorchimerism, respectively. At 2 year post-transplant, the cumulative incidence (CI) of acute GVHD grade II-IV and grade III-IV was 26.3% and 8.4%, respectively, whereas CI of chronic GVHD was 30.9% with extensive chronic GVHD 17.8%. Leukemia free survival (LFS), overall survival (OS), CI of relapse, non-relapse mortality (NRM) at 2 years for the whole group was 31.3%, 36.8%, 51.1% and 17.6%, respectively, while 2-year GVHD-free, relapse-free survival (GRFS) was 19.8%. LFS, OS, GRFS, CI of relapse and NRM at 2 years for patients transplanted in CR1 was 38.4%, 44.5%, 23.8%, 46% and 15.7%, respectively. For patients with active disease these outcomes were 14.6%, 18.5%, 9.6%, 63.5% and 21.9%, respectively (Figure A, B). Patients ages 40-60 years transplanted in CR1 with MAC demonstrated lower relapse (40.2% vs. 51% with RIC, p=0.005), offset by a higher NRM (18.2% vs 9.8% RIC, p=0.037), associated with higher incidence of acute GVHD, and a non-significant difference in LFS (Figure C, D). In multivariable analysis (MVA) for the entire group, advanced age, transplantation in active disease, secondary AML and presence of deletion or monosomy 5 or 7 predicted poor LFS and OS. All of these factors as well as year of transplant (before 2010) also predicted poor GRFS, while conditioning intensity (MAC vs RIC) and donor type did not influence survival outcomes. Prognostic factors for relapse were age, secondary AML, active disease at transplant and presence of deletion or monosomy 5, while prognostic factors for NRM were older age, active disease, use of a mismatched unrelated donor and deletion or monosomy 7. Conclusions In this largest analysis of complex karyotypes AML patients, relapse remains the most common cause of treatment failure with 45% for patients in CR1 and 63.5% for patients not in remission relapsing after transplant. The only modifiable factorsat this time are performing transplantation in CR1 as soon as the donor is available. Control of GVHD might allow younger patients receiving MAC to have a lower NRM and improved LFS. Novel approaches are needed to decrease relapse rate and improve survival in these patients. Table Multivariable analysis for patients with CK AML. Table. Multivariable analysis for patients with CK AML. Figure A. CI of relapse for all patients and patients in CR; B. LFS for all patients and patients in CR; C. CI of relapse for patients age 40-60 years in CR with MAC, RIC; D. LFS for patients age 40-60 years in CR with MAC, RIC. Figure. A. CI of relapse for all patients and patients in CR; B. LFS for all patients and patients in CR; C. CI of relapse for patients age 40-60 years in CR with MAC, RIC; D. LFS for patients age 40-60 years in CR with MAC, RIC. Disclosures Ciurea: Cyto-Sen Therapeutics: Equity Ownership; Spectrum Pharmaceuticals: Other: Advisory Board. Champlin:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.

scholarly journals CD19-CAR-T Therapy Followed By Allogeneic Hematopoietic Stem Cell Transplantation in Refractory/Relapsed and High Risk B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2660-2660 ◽  
Author(s):  
Yanli Zhao ◽  
Jianping Zhang ◽  
Deyan Liu ◽  
Min Xiong ◽  
Zhijie Wei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Median Time ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Introduction: CD19-CAR-T cells induce high rates of initial response among patients with refractory/relapsed and MRD positive high risk B-cell acute lymphoblastic leukemia (B-ALL). Afterwards allogeneic hematopoietic stem cell transplantation (HSCT) can further reduce relapse rate. Our previous results had shown that CR obtained by CD19 CAR-T had comparable significance to CR by chemotherapy before Allogeneic HSCT in B-ALL. Patients and Methods: Between July 2015 and Mar 2018, consecutive 135 patients with refractory/relapsed or high risk B-ALL obtained CR with CD19-CART therapy followed by allogeneic HSCT were retrospective analyzed. Median follow-up of survivors was 13 months (range, 3-32 months). Results: The median age was 11 (2-49) years. The median disease course before transplant was 21(4-143) months. The median time from CART therapy to HSCT was 69 (35-312) days. Disease status was 108 cases relapsed diseases, 11 cases refractory, and 16 persistent/recurrent measurable residual diseases (MRD). MRD pre-conditioning measured by flow cytometry and QT-PCR was positive in 20(14.8%) subjects. Donor source was haploidentical donors in 107(79.3%), identical sibling in 7(5.1%), and unrelated in 21(15.6%). Most subjects (87.4%) received conventional myeloablative pretransplant conditioning with total body radiation (TBI), the rest with busulfan (Bu). Antithymocyte globulin was used in haploidentical and unrelated transplants. Cyclosporine, short-term methotrexate, and mycophenolate mofetil were employed for GVHD prophylaxis. There were no cases of graft-failure except one early death on Day 0 for septic shock. The median time to neutrophil engraftment was 14 days (10, 26 days), and median time to platelet engraftment 14 days (5, 70 days). The incidences of non-relapse mortality within 100 days were 4.4% (0.8, 7.9%) The incidence of grades II-IV acute graft-versus-host disease (GvHD) were 32.1% (24.3, 39.9%) and grades III-IV GvHD 10.5% (5.4, 15.6%). Chronic GvHD and extensive chronic GvHD were 69.7% (60.7, 78.7%) and17.6% (10.7, 24.5%). Cumulative incidence of relapses (CIRs) at 2-year was 11.1% (5.4, 16.8%). There were totally 14 subjects relapsed after HSCT, among which 8 were CD19 negative relapse, 5 CD19 positive and 1 partial CD19 positive. And among the 8 CD19 negative relapse after transplant, 4 subjects had CD19 negative MRD before conditioning. Leukemia-free survival (LFS) was 76.5% (64.2, 88.8%) and overall survival (OS) was 80.8% (72.6, 89.0%) at two years after transplant. In multivariate analysis subjects who were MRD- positive pre-transplant had a higher 2-year CIR (43.5% [18.4, 68.6%] vs. 5.9% [1.2, 10.6%]; p=0.000) and worse 2-year OS (61.5% [35.6, 87.4%] vs. 83.6% [75, 92.2%]; p=0.034). Conclusions: Our clinical results showed that CART therapy followed by allogeneic HSCT was a promising modality for refractory/relapsed B-ALL. CD19 negative relapse accounted for most relapse after allogeneic HSCT. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Novel Improvement of Haploidentical Hematopoietic Stem Cell Transplantation for Advanced Refractory/Relapsed Acute Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4593-4593
Author(s):  
Fei Pan ◽  
Peihua Lu ◽  
Zhijie Wei ◽  
Rong Yang ◽  
Shuquan Ji
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Median Time ◽  
Mononuclear Cells ◽  
Chronic Gvhd ◽  
Hematopoietic Stem

Introduction The advanced refractory/relapsed acute leukemia has a very dismal prognosis even with the salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT). To develop a novel transplant protocol to achieve a rapid engraftment and quick graft-versus leukemia (GVL) effect is crucial. Based on previous observation, the G-CSF primed bone marrow (BM) plus peripheral blood mononuclear cells (PBMNCs) could not only increase mononuclear cells and CD34 cells, but also change T-cell biology by down-regulating the expression of adhesion and CD28/B7 molecules and increase the absolute number of D2APCS, which promotes a T-cell shift from T1 to T2 subset to secrete a higher anti-inflammatory cytokines of IL-4 and IL-10. After going through a rigorous conditioning, the recipients' T-cells are incapable to attack host. We propose that reinfusion of G-CSF primed donor PBMNCs to recipient on transplant day + 6 may cross mismatched MHC barrier thus accelerating engraftment. Patients and Methods From April 2018 to June 2019, 30 advanced-stage patients with refractory/relapsed acute leukemia were enrolled and underwent a salvage haploidentical (haplo)-HSCT. The median age was 12 (2-63) years with M/F ratio of 17/13. There were 21 patients with acute myelocytic leukemia (AML, 70%), 4 -cell acute lymphoblastic leukemia (B-ALL, 13%), 2 biphenotypic acute leukemia (BAL, 7%), 1 juvenile myelomonocytic leukemia (JMML, 3%), and 2 T-lymphoblast leukemia (T-LBL, 7%). The median BM blasts were 40% (5%-90%). Twenty-eight patients received a conditioning regimen including fludarabine 30mg/m2/d×4 day, cytarabine 2.0g/m2/d×4 days, busulfan 3.2mg/kg/d Q6h×4days, cyclophosphamide 1.5g/m2/d×2 days and melphalan 110mg/m2/d×1 day. Two patients with T-LBL received BCNU+Etoposide+Cytarabine+Melphalan (BEAM) regimen. Graft-versus-host disease (GVHD) prophylaxis contained methotrexate (MTX), cyclosporine A (CsA) and mycophenolate mofetil (MMF), plus ATG (Rabbit anti-human thymocyte immunoglobulin, Sangstat) 1.5mg/kg/d iv daily from day -4 to -1 and additional 1.5mg/kg on day +7 (total dose of 7.5 mg/kg). In addition, anti-CD25 monoclonal antibody (basiliximab) 20 mg on day+1 and +4 was given iv. Donors were primed with G-CSF at 3-4 ug/kg/d sq d1-5. On day 4 of G-CSF, donor BM cells were harvested and were infused unmanipulated on the same day to patient on transplant day 01. On day 5 of G-CSF injection, donor primed PBMNCs were harvested, part of which were immediately infused unmanipulated to recipient on transplant day 02. Part of the cells were cryopreserved and stored in the liquid nitrogen, which were then thawed and reinfused unmanipulated to recipient on day +6 (Table 1). Results All patients achieved a trilineage engraftment with a median time of 13.5 (5-16) days. The median neutrophil and platelet engraftment were 13 (11-19) days and 10 (5-22) days respectively (Fig.1). Among 29 evaluable patients, acute GVHD occurred in 10 (34.5%, Fig. 2) with a median time of 32 (14-60) days, including 5 cases (17%) of grade Ⅱ, 3 (10%) of grade Ⅲ and 2 (7%) of grade Ⅳ. Among the 28 evaluable patients for chronic GVHD, only 6 (21.4%, Fig.3) developed limited chronic GVHD with a median time of 103 (90-180) days. Twenty seven out of thirty (90%) patients achieved disease-free survival (DFS) with a median follow-up time of 6 (5-14) months. Three patients died from transplant related complication, including infection for 2 and GVHD for 1 respectively. Conclusion In this study, with an intensive myeloablative condition and salvage haplo-HSCT, by reinfusing additional unmanipulated donor PBMNCs to recipients on day +6 during their transplantation, a short engraftment time without engraftment failure, low lethal GVHD incidence, and a lower infection rate were able to be achieved. More importantly, most patients remain DFS at a median follow-up time of 6 months. Despite short-term follow-up. the outcomes are particularly encouraging. Disclosures No relevant conflicts of interest to declare.

Fludarabine/Melphalan Conditioning for Allogeneic Stem Cell Transplantation (SCT) in Elderly Patients with AML/MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5410-5410
Author(s):  
Glen A. Kennedy ◽  
Jason Butler ◽  
Simon Durrant ◽  
Geoff R. Hill ◽  
Robyn Western ◽  
...  
Keyword(s):  
Stem Cell ◽  
Elderly Patients ◽  
Survival Data ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Term Survival ◽  
Phase 2 Trial ◽  
Kaplan Meier

Abstract Aims: To assess the tolerability and efficacy of a reduced-intensity, non-TBI based allogeneic SCT conditioning regimen utilising fludarabine and melphalan (FluMel) in elderly patients with AML /MDS. Methods: Fludarabine (25mg/m2 D-7 to D-3) and melphalan (120mg/m2 D-2) allogeneic SCT was performed as part of a prospective phase 2 trial to assess the tolerability of the preparative regimen across a range of haematological malignancies. For this analysis, all patients aged &gt;50yrs with AML /MDS who underwent FluMel transplantation were retrospectively reviewed. Standard GVHD prophylaxis was cyclosporine + methotrexate (D1–11). Both HLA-matched siblings and volunteer unrelated donors (VUD) were permitted as stem cell donors. Graft source was G-CSF stimulated PBPC; all grafts were T-cell replete. Survival data was calculated utilising the Kaplan-Meier product-limit method. Results: In total 20 patients &gt;50yrs (16M and 4F) had received FluMel allogeneic SCT for AML (n=15) or MDS (n=5). Median age at SCT was 60yrs (range 50 to 67yrs). AML transplants were performed in CR1 (n=5), early 1st relapse (n=3), CR2 (n=3), MDS phase post CR1 (n=2), early 3rd relapse (n=1), and primary refractory disease (n=1); 7/15 AML patients had intermediate risk and 7/15 poor risk cytogenetics (1 no data available). All 5 MDS patients were previously untreated; all had INT-1 risk disease on IPSS. Donors were HLA-matched siblings in 14 cases and VUD in 6. A total of 6 patients have died, including 2 prior to engraftment (1 of hepatic failure and 1 from idiopathic pneumonia syndrome) and 4 after day 75 (relapsed AML 2 cases; acute GVHD 1 case; multi-organ failure 1 case). All 18 patients who survived the initial cytopenic period achieved durable engraftment; 10 (50%) subsequently developed acute GVHD, including grades II-IV in 9 cases (45%) and grades III-IV in 3 (15%). Of the 12 patients with follow-up &gt;3mths post-SCT, 9 (75%) developed chronic GVHD, which was extensive-stage in 8 (67%). At a median follow-up of 2.4 yrs (range 0.1–5.2 yrs), overall and event-free survival at 2 years for the whole cohort are both 66%. Conclusions: Our experience suggests that allogeneic SCT with FluMel conditioning in elderly patients AML /MDS is associated with acceptable treatment-related toxicity and significant long-term survival. Further studies on this transplant approach in older patients are warranted.

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