scholarly journals Cluster of Fulminant Toxoplasmosis in T-Cell Depleted (TCD) and Cord Blood (CB) Stem Cell Transplant (SCT) Recipients: Impact of Aggressive Prophylaxis and Routine Monitoring By Toxoplasma PCR for High Risk Patients

2015 ◽  
Vol 21 (2) ◽  
pp. S303
Author(s):  
Yao-Ting Huang ◽  
Ann A. Jakubowski ◽  
Hugo Castro-Malaspina ◽  
Juliet Barker ◽  
Guenther Koehne ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Cord Blood ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
High Risk Patients ◽  
Routine Monitoring ◽  
Risk Patients

Comorbidity and Outcomes for Patients Over Age 65 Years Treated with Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndrome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2032-2032 ◽  
Author(s):  
Henry J. Conter ◽  
Nhu-Nhu Nguyen ◽  
Gabriela Rondon ◽  
Julianne Chen ◽  
Elizabeth J Shpall ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cumulative Incidence ◽  
Stem Cell Transplant ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
High Risk Patients ◽  
Risk Patients ◽  
Acute Myelogenous ◽  
Related Mortality

Abstract Abstract 2032 Background: Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) preferentially afflict patients 65 years of age and older. Patients in this age group are likely to have underlying comorbid conditions. These comorbidities affect treatment planning decisions and clinical outcomes. Here we report comorbidity-stratified outcomes of patients older than 64 treated at MD Anderson Cancer Center from 1996 until 2011, inclusive, treated with allogeneic stem cell transplant (ASCT). Methods: 182 patients older than 64 received an ASCT for AML (n=143) or MDS (n=39). Patient charts were reviewed and comorbidity data abstracted using a standardized form. Burden of comorbidity was assessed using the Hematopoetic Stem Cell Transplant-Specific Comorbidity Index (HSCT-CI). Low-risk, intermediate-risk, and high-risk patients were categorised at 0, 1–2, and >=3 points as per the HSCT-CI. 157 patients were evaluable for pre-transplant comorbidity. Outcomes of interest were cumulative incidence of transplant-related mortality (TRM), cumulative incidence of relapse-related mortality (RRM), incidence of acute and chronic graft-versus-host disease (GVHD), and overall survival (OS). These were estimated from the date of transplantation. Results: The median age of transplanted patients was 67 (range 65–79), and 37 patients age 70 and older were treated. The majority of patients were intermediate-risk and high-risk patients (table), 9 patients had HSCT-CI scores of >=5. Median follow-up for alive patients was 12.6 months (n=63; range 0–118). Cumulative incidence of TRM was 6% at 100 days, 14% at 1 year, 23% at 2 years, and 36% at 5 years (figure). Cumulative incidence of RRM was 36% at 1 year, 42% at 2 years, and 47% at 5 years. HSCT-CI did not independently predict for either TRM or RRM (log-rank test p=0.95). The incidence of grade III and IV acute GVHD was 10% of all patients. The cumulative incidence of chronic GVHD was 25% at 1 year, 27% at 2 years, and 30% at 5 years, with no association between GVHD and HSCT-CI comorbidity. Conclusion: ASCT is a curative option for selected patients over age 64. HSCT-CI did not predict TRM or survival on this cohort of high-risk patients. Disease relapse was of greater concern than TRM, and so novel approaches to relapse prevention are needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Optimizing Autologous Stem Cell Transplant for High-Risk Patients with Plasma Cell Dyscrasias

2018 ◽  
Vol 24 (3) ◽  
pp. S135
Author(s):  
Ehsan Malek ◽  
Gina Hoffman ◽  
Richard Creger ◽  
Brenda Cooper ◽  
Merle Kolk ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Plasma Cell ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
High Risk Patients ◽  
Risk Patients ◽  
Plasma Cell Dyscrasias

scholarly journals Treosulfan/fludarabine as an allogeneic hematopoietic stem cell transplant conditioning regimen for high-risk patients

2008 ◽  
Vol 83 (9) ◽  
pp. 717-720 ◽  
Author(s):  
Donatella Baronciani ◽  
Alessandro Rambaldi ◽  
Anna Paola Iori ◽  
Paolo Di Bartolomeo ◽  
Federica Pilo ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
High Risk Patients ◽  
Risk Patients

scholarly journals A Single Center Retrospective Analysis of Letermovir for Cytomegalovirus Prophylaxis after Allogeneic Stem Cell Transplant in Cytomegalovirus Seropositive Recipients or Donors

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2864-2864
Author(s):  
Lawrence Liu ◽  
Alicia Yn ◽  
Feng Gao ◽  
Marissa Olson ◽  
Mallory Crain ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
High Risk Patients ◽  
Risk Patients ◽  
Igg Level ◽  
Cmv Reactivation ◽  
Related Mortality

Abstract Background: Up to 70% of allogeneic stem cell transplant (alloSCT) recipients who are cytomegalovirus (CMV) seropositive experience CMV reactivation and up to a third are complicated by end-organ disease. Letermovir, an antiviral agent targeting CMV, is FDA-approved for prophylaxis of CMV reactivation in CMV seropositive recipients of alloSCT. 1-4 In CMV seropositive recipients, letermovir use up to week 14 after alloSCT has demonstrated a significantly lower incidence of clinically significant CMV infection (csCMVi) and an overall mortality benefit as far as 24 weeks after transplant. 5-8 However, data on csCMVi beyond 24 weeks is lacking. Additionally, more information is needed on letermovir use in patients who had prior alloSCT, are CMV seronegative, have a detectable CMV viral load but without csCMVi, and/or are high risk*. Methods: This is a single-center, retrospective, comparative cohort analysis of 524 patients who received alloSCT at Barnes-Jewish Hospital from January 2016 to June 2019. Of those, 191 patients were excluded because both the recipient and donor were seronegative for CMV. Patient information was obtained from the electronic medical record systems after IRB approval of the protocol. Gray's sub-distribution methods (while account for death as competing risk) were used to calculate the incidence of csCMVi and to assess the effect of letermovir on csCMVi. Univariate and multivariate Cox proportional hazards models were fitted for the effect of letermovir on overall survival (OS), and time-dependent Cox model was used to determine the effect of csCMVi on OS. Results: Out of 333 patients, 149 received letermovir. The median follow-up period was 13.38 months (0.033 to 63.8 months). A univariate analysis demonstrated that csCMVi was associated with worse OS (HR 2.173, 95% CI 1.602-2.948). Among those who received letermovir, there were reductions in csCMVi for the overall cohort and for high-risk patients at 100 days, 180 days, and 365 days after alloSCT. In seropositive recipients receiving seropositive alloSCT (CMV +/+), there were reductions in csCMVi at days 100, 180, and 365 after transplant. In seropositive recipients receiving seronegative alloSCT (CMV +/-), there was a reduction in csCMVi at 100 days after transplant. There was a reduction in CMV-related mortality at day 180 post-transplant (p=0.03) but not at day 365 (p=0.46). Additionally, for the overall cohort, the letermovir group showed worse OS from days 180-365 (HR 1.938, 95% CI 1.143-3.285). In CMV seronegative patients receiving seropositive SCT (CMV -/+), no difference in csCMVi was detected at days 100, 180, and 365. A landmark analysis of Day 100 IgG level effect on csCMVi incidence demonstrated that lower IgG level (<485) is associated with higher csCMVi rates after Day 100 (p=0.004). Day 100 CD4 level was not found to be predictive of csCMVi (p=0.744). Conclusion: Letermovir prophylaxis reduces csCMVi overall and in high risk and CMV seropositive patients. We observed a reduction in CMV-related mortality at 180 days after transplant with letermovir prophylaxis. A worsening of OS after day 180 and a trend towards worse non-relapse mortality was surprising and may be related to a higher degree of immunosuppression associated with post-transplant cyclophosphamide (PTCy) use, haploidentical SCT, thymoglobulin use, prior SCTs, and CMV high-risk* patients. Additionally, letermovir was stopped at day 100 at which point survival worsens and the incidence of csCMVi precipitously increases. Our results suggest that there may be additional benefit to extending letermovir therapy past day 100 in the high-risk groups, haploidentical SCT group, patients with low IgG levels at day 100, and subclinical CMV viremia. *High risk patients were defined as those receiving haploidentical, mismatched related, mismatched unrelated, umbilical cord blood, T-cell depleted graft stem cell transplants or immunosuppression with methylprednisolone > 1 mg/kg or 2 or more immunosuppressants. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Fludarabine (Flu) Based Cytoreductive Regimen and T-Cell Depleted Grafts from Unrelated or Mismatched Related Donors for the Treatment of High Risk Patients with Fanconi Anemia (FA).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2152-2152 ◽  
Author(s):  
Farid Boulad ◽  
Arleen D. Auerbach ◽  
Nancy A. Kernan ◽  
Trudy N. Small ◽  
Susan E. Prockop ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Fanconi Anemia ◽  
Hla Antigens ◽  
High Risk Patients ◽  
Cell Transplants ◽  
Risk Patients ◽  
Stem Cell Transplants ◽  
Disease Free

Abstract Between 05/98 and 06/04, 15 consecutive patients with FA received hematopoietic stem cell transplants (SCT) from alternative donors at our Center. There were 7 males and 8 females aged 5 to 24 years (median 11.5). Hematologic diagnoses included aplastic anemia (AA) (N=5), myelodysplastic syndrome (MDS) in RAEB (N=4), RAEBT (N=1) or acute myelogenous leukemia (AML) (N=5). High risk features included: Age > 20 years (n=4), prior multiple transfusions (n=11), prior androgen treatment (n=12), prior infections (n=10), or advanced MDS or AML (n=9). Eight pts had related mismatched donors transplants with respective matching at 3/6 (6/10), 4/6 (6/10), 4/6 (7/10) (n=2)), 5/6 (8/10) (n=3) and 5/6 (9/10) HLA-antigens. Seven pts had unrelated donors transplants with respective matching at 5/6 (7/10), 5/6 (8/10) (n=2), 5/6 (9/10) and 6/6 (10/10) (n=3) HLA-antigens. Cytoreduction included single dose total body irradiation (SDTBI) (450 cGy), fludarabine (Flu) (30 mg/m2 x 5) and cyclophosphamide (Cy) (10 mg/Kg x 4). Immunosuppression included rabbit anti-thymocyte globulin (Thymoglobulin) and tacrolimus for all patients. Grafts were G-CSF mobilized CD34+ and E-rosette negative (E-) peripheral blood stem cell transplants for 12 pts and soybean agglutinin negative (SBA-) and E-rosette negative marrow transplants for 3 pts. Cell doses of the grafts were 1.5 – 29.6 x 106 CD34 cells/Kg and 0 – 26 x 103 CD3 cells/Kg. As evidenced by RFLP or FISH, all 15 evaluable pts were fully engrafted and complete chimeras. Fourteen pts were evaluable for graft-versus-host disease (GvHD). GvHD of the skin and of the gut was suspected in two pts but resolved completely prior to immunosuppressive treatment. With a median follow-up of 2.5 years (range 0.2–6), 13 of 15 pts are alive and 11 of 15 are alive disease-free. There were two deaths: one pt died from sepsis/ARDS at 2 months post SCT and one pt from pneumonitis/ARDS and EBV-infection 6 months post SCT. Three pts relapsed (MDS-RAEB x 1 – AML x 2): One pt relapsed 7 months post transplant, received a 2nd transplant from the same donor following busulfan and Flu and is alive, disease-free 18 months post SCT, while the other two pts are awaiting a second SCT. In summary, this cytoreductive regimen used with T-cell depleted stem cell transplants from unrelated or HLA-mismatched related donors for the treatment of high risk patients with Fanconi anemia, results in rapid hematopoietic engraftment and lymphohematopoietic reconstitution with minimal GVHD and a high disease-free survival.

Feasibility and Efficacy of Tandem Autologous-Allogeneic Transplantation in a Cohort of 111 Patients Affected By High-Risk Hodgkin's and Non-Hodgkin's Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3863-3863
Author(s):  
Roberto Crocchiolo ◽  
Luca Castagna ◽  
Sabine Fuerst ◽  
Jean El Cheikh ◽  
Barbara Sarina ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cord Blood ◽  
Disease Status ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Significant Prognostic Factor ◽  
Grey Zone ◽  
High Risk Patients ◽  
Risk Patients

Abstract Introduction: although high-dose chemotherapy (HDC) is the golden standard for the treatment of many relapsed or refractory lymphomas, the outcome is still unsatisfactory especially in some subsets of patients with adverse prognostic features. To improve these results, we treated high-risk patients with a tandem strategy associating debulking with HDC followed by autologous stem cell transplantation (ASCT) and subsequent adoptive immunotherapy consisting in allogeneic SCT (tandem auto-allo). We report here the outcome of 111 lymphoma patients undergoing this procedure; in addition, the role of two ASCT conditioning regimens is discussed. Patients and Methods: adult patients consecutively treated at two centers (Milan, Italy and Marseille, France) were included. Criteria for receiving tandem auto-allo were: refractory disease after first-line therapy, less than CR after first salvage treatment, histology of transformed follicular, mantle-, T- and NK-cell lymphoma, relapse after prior ASCT, multiple relapses. Disease evaluation was performed by using PET scan starting from 2003. Results: 111 consecutive patients with HL or NHL were transplanted from June 2002 to September 2013. Main characteristics are shown in Table 1. Median interval between ASCT and allogeneic SCT was 85 days (range: 36-235). Sixty-two patients (56%) received BEAM (8 of them without BCNU) and 46 (41%) high-dose Melphalan (HD-Mel, 100-200 mg/m2); 3 patients received other regimens. Main characteristics were not significantly different between BEAM and HD-Mel groups with the exception of the use of more alternative donor (i.e. non HLA-identical) in the HD-Mel group: 33% vs. 13%, p=0.01. Disease status before ASCT was: CR (n=47), PR (n=38), SD (n=10), PD (n=16). Grade 3-4 mucositis occurred in 49 patients (44%) and documented infections during hospital stay in 30 (27%), without differences between BEAM and HD-Mel groups, p=0.57 and p=0.14. Disease status before allogeneic SCT was: CR (n=79), PR (n=22), SD (n=5), PD (n=5). Among the 64 patients with active disease before ASCT, the overall response rate was 87% (n=56 responders) and the rate of CR was 53% (n=34), these latter adding to the 45 (out of the 47) patients in CR before ASCT; nine patients (8%) progressed between ASCT and allogeneic SCT. Again, no differences were observed in terms of response among BEAM and HD-Mel group (p=0.28). Allogeneic SCT was performed after NMA (n=43), RIC (n=66) or MA (n=2) conditioning; donor was either HLA-identical (n=86), MUD 9/10 (n=2), haploidentical (n=20) or cord blood (n=3). After a median follow-up of 38 months after allogeneic SCT, 3-y OS of entire cohort was 68% (95% CI: 59-77), 3-y PFS was 61% (52-70), rates of acute GvHD grade 2-4 and chronic GvHD were 28% and 38% respectively. TRM rate was 18% (n=20). Last relapse event occurred at day +853. No difference between BEAM and HD-Mel group was observed for OS (73% and 64% respectively, p=0.40) or TRM (19% and 13%, p=0.44). CR before allogeneic SCT confirms to a major prognostic factors for OS (Figure 1), whereas donor type did not significantly impact on survival (p=0.68). No survival difference was observed between HL and NHL (p=0.53). Conclusions: tandem auto-allo confirms to be a feasible and effective therapeutic strategy in those lymphoma patients whose prognosis is expected to be unsatisfactory with ASCT alone. BEAM vs. HD-Mel appeared to be similar in terms of extrahematological toxicity, disease response and survival. Disease status before allogeneic SCT confirms to be a significant prognostic factor, underlying the importance of high-dose chemotherapy followed by ASCT as further tumor shrinking before allogeneic immunotherapy in this setting of high-risk patients. Table 1. Main patients’ and transplant characteristics Variable Value % N 111 100% Pt's age (median) 44 range:16-69 Gender M 66 59% F 45 41% Disease HL 44 40% DLBCL 12 11% FL 21 19% Transf FL 9 8% MCL 9 8% MZL 1 1% T lymph 13 12% Grey zone 1 1% NK lymphoma 1 1% Indication for tandem auto-allo 1ary refractory 28 25% no CR after salvage 43 39% histology 10 9% relapse after prior ASCT 6 5% multiple relapse 24 22% Prior therapy lines (median) 2 range: 0-7 Prior radiotherapy 26 23% ASCT conditioning BEAM 54 49% EAM 8 7% HD-Mel 100 1 1% HD-Mel 140 12 11% HD-Mel 200 33 30% other 3 3% Allogeneic stem cell donor HLA-id sibling 62 56% MUD 10/10 24 22% MUD 9/10 2 2% haplo 20 18% cord blood 3 3% Figure 1. OS according to disease status after ASCT. Figure 1. OS according to disease status after ASCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Phase I/IIa Study of Genetically Engineered NY-ESO-1 SPEAR T-Cells Administered Following Autologous Stem Cell Transplant in HLA-a*02+ Patients with Advanced Multiple Myeloma: Long Term Follow-up (NCT01352286)

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 845-845
Author(s):  
Aaron P. Rapoport ◽  
Edward A Stadtmauer ◽  
Karen Chagin ◽  
Thomas Faitg ◽  
Malini Iyengar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Adverse Events ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Genetically Engineered ◽  
Cell Transplant

Abstract Background: NY-ESO-1 and LAGE-1a are cancer-testis antigens that are overexpressed in patients with multiple myeloma (MM), and the incidence of these antigens correlates with tumor proliferation and other high-risk features. Genetically engineered NY-ESO-1 SPEAR (specific peptide enhanced affinity receptor) T-cells (NY-ESO-1c259T cells) recognize the peptide sequence SLLMWITQC expressed by NY-ESO-1 or LAGE-1a in the context of HLA-A*02 presentation. This study evaluated treatment with NY-ESO-1SPEAR T-cells post-autologous stem cell transplant (ASCT) in patients with advanced MM. Methods: Eligible patients were HLA-A*02:01, 02:05 or 02:06 positive, with refractory, relapsed or high risk MM associated with one or more adverse cytogenetic abnormalities. Eligible patients' tumors also expressed NY-ESO-1 and/or LAGE-1a by qPCR. The primary study endpoint was safety. Secondary objectives included overall response rate (ORR) (sCR+CR+VGPR+PR) evaluated with the International Myeloma Working Group Criteria (Rajkumar S.V. et al., Blood 2011), progression-free survival (PFS), overall survival (OS), best overall response (BOR), duration of response (DOR), as well as gene-marked cell persistence. Lymphocytes were obtained by leukapheresis, isolated, activated, transduced to express NY-ESO-1c259T cell receptor, and expanded using anti-CD3/anti-CD28 immunomagnetic beads. While the SPEAR T-cells were being manufactured, stem cell mobilization was conducted using 1.5 g/m2 of cyclophosphamide plus G-CSF, and stem cells were collected (minimum: 2 × 106 CD34+ progenitors/kg). Once the manufactured product was ready, high-dose melphalan (140-200 mg/m2) was given 2 days before stem cell infusion. Two days after the stem cell infusion, the SPEAR T-cells were infused (median dose 3.1 × 109 of transduced T-cells, range 0.5-5.1 × 109). Disease was assessed at days 42, 100, 180, 270 and 360 post-T-cell infusion, and then every 3 months. Patients meeting the criteria for lenalidomide maintenance therapy received 10 mg/day starting around day 100 post-ASCT. Results: Twenty-five patients were enrolled, and all have been treated. Median age at enrollment was 61 yr (range 45 - 72); 60% were male. Based on analyses through July 2017, ORR at day 100 was 76% (1 sCR; 12 VGPR; 6PR), and at year 1, 13 patients were progression free (52%) of which 11 were responders (1 sCR; 1 CR; 8 VGPR; 1 PR). Three patients remain disease progression-free at 39, 56 and 61 months post T-cell infusion. Median PFS was ~13 months (range 3-61 months). Eleven of 25 patients (44%) are alive, and median survival was ~35 months (range 6-68 months). The most common adverse events (experienced by >70%) were diarrhea (100%), nausea (100%), anemia (96%), decreased appetite (92%), thrombocytopenia (92%), fatigue (88%), pyrexia (84%), rash (84%), hypokalemia (76%), febrile neutropenia (72%) and vomiting (72%). Autologous GVHD (24%) was reported in 6 patients (3 G3, 3 ≤G2); all resolved with corticosteroids and supportive therapy. No fatal adverse events have been reported. Conclusions: NY-ESO-1 SPEAR T-cell therapy in the setting of autologous stem cell transplant has promising efficacy and acceptable safety. GVHD, which manifests in a similar way as reported in prior transplant studies and is more frequent with adoptive T cell transfer (engineered or not engineered), appears manageable with appropriate supportive care. Analyses of transduced cell persistence, T-cell clonality, and minimal residual disease (MRD) genetic studies are ongoing and will be presented along with the efficacy and safety data for all 25 patients. Disclosures Chagin: Adaptimmune: Employment. Faitg: Adaptimmune: Employment. Iyengar: Adaptimmune: Employment. Trivedi: Adaptimmune: Employment. Norry: Adaptimmune: Employment. Holdich: Adaptimmune: Employment. Binder-Scholl: Adaptimmune: Employment. Amado: Adaptimmune: Employment. Fang: Adaptimmune: Employment.

Sign in / Sign up

Export Citation Format

Share Document