scholarly journals Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in Japanese patients after allogeneic stem cell transplantation.

2021 ◽  
Author(s):  
Marika Watanabe ◽  
Kimikazu Yakushijin ◽  
Yohei Funakoshi ◽  
Goh Ohji ◽  
Hironori Sakai ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Healthy Volunteers ◽  
Cell Transplantation ◽  
Japanese Patients ◽  
Serious Adverse Events ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Grade 3 ◽  
Almost All

Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccine in HSCT patients remains to be investigated. We prospectively evaluated the safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) got seroconversion of anti-S1 IgG. Median optical density of antibody levels in HSCT patients with low IgG levels (< 600 mg/dL), steroid treatment, or low lymphocytes (< 1000 /μL) was significantly lower than that in the other HSCT patients. There were no serious adverse events (> Grade 3), no new development or exacerbation of graft-versus-host disease after vaccination. We concluded BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients.

Prospective Study of Post-Transplant Microangiopathy in Allogeneic and Autologous Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5037-5037
Author(s):  
Zella Rose Zeigler ◽  
R. Shadduck ◽  
John Lister
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lactic Dehydrogenase ◽  
Marrow Transplant ◽  
Post Transplant ◽  
Institutional Review ◽  
Pennsylvania Hospital ◽  
Grade 3 ◽  
Almost All

Abstract Thrombotic thrombocytopenic purpura-hemolytic uremic syndromes (TTP-HUS) have been described as specific sequelae following stem cell transplantation (SCT).Twenty-two patients undergoing autologous SCT and thirty-three patients undergoing allogeneic stem cell transplantation were prospectively evaluated on days 0, 7, 14, 30, 60, 90, 120 following SCT for the development of Post-Transplant Microangiopathy (PTM) based upon a rising lactic dehydrogenase level and percent fragmented cells (FC). The protocols were approved by the Institutional Review Board of the Western Pennsylvania Hospital where the studies were performed. The grades of PTM were based upon the criteria described by Zeigler et al, Bone Marrow Transplant, 1995) as follows: Grade 0: Normal LDH level and normal percentage fragmented cells (0–1.2%), Grade 1: Increased Fragmented Cells (FC) with normal LDH level, Grade 2: Increased LDH level that is rising with 1.2–4.8% FC, Grade 3: Increased LDH level with 4.9–9.6% FC and Grade 4: Increased LDH level with &gt;9.6% FC. The data is shown below in tabular form. These results indicate that almost all patients have increased fragmented cells following both autologous and allogeneic SCT. The median percent fragmented cells in both allogeneic and autologous SCT patients without evidence for PTM was 1.4% with a range of 0–5.2% Moreoeve the LDH level x ULN was 0.7 with a range of 0.5–1.8 x ULN in patients without evidence for PTM. The table below shows the data for the development of PTM in both allogeneic and autologous SCT patients with regard peak grade. Only two autologous patients had no increase in FC. The Grade of PTM was significantly lower in the autologous SCT patients compared to the allogeneic SCT patients. The table below lists the grades of PTM and the day of the peak Grade of PTM in both types of SCT patients. The Grades of PTM, peak LDH level and highest percent FC were higher in the allogeneic SCT patients. Eleven of twenty-two (50%) of the autologous SCT patients compared to thirty/thirty-three (91%) of the allogeneic SCT patients (p &lt;0.001) had evidence for PTM (grades 2 to 4). PTM Grade Autologous Allogeneic p Grade 0–1 (no PTM) 11/22 (50%) 3/33 (9%) &lt;0.001 Grade 2 10/22 (45%) 10/33 (30%) NS Grade 3 1/22 (5%) 13 (39%) &lt;0.01 Grade 4 0/22 (0%) 7/33 (21%) NS Day to Peak TM 31 (3–96) 26 (7–120) NS Peak LDH x ULN 1.1 (0.7–31.9) 2.5 (0.9–14.8) &lt;0.001 Peak % FC 2.3 (0.5–4.9) 5.2 (1.9–19.2) &lt;.001

Phase I Study of Ipilimumab (Neutralizing Monoclonal Anti-CTLA4 Antibody) To Treat Relapse of Malignancy after Allogeneic Hematopoietic Stem Cell Transplantation: Evidence of Tumor Regression without Induction of GVHD.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 410-410
Author(s):  
Asad Bashey ◽  
Bridget Medina ◽  
Sue Corringham ◽  
Mildred Pasek ◽  
Ewa Carrier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Negative Regulator ◽  
Hematopoietic Stem ◽  
Anti Cancer ◽  
Grade 3

Abstract Failure of adoptive cellular immunotherapy is an important cause of relapse of malignancy (RM) and death following allogeneic hematopoietic stem cell transplantation (allo-HCT). CTLA-4 is a negative regulator of activated T-cells. Therapeutic blockade of CTLA-4 has demonstrated potent anti-cancer effects in animal models, and in patients with some solid tumors. Although CTLA-4 blockade may augment graft-versus-malignancy following allo-HCT, GVHD and other immune complications may also be increased. We report the results of a completed phase I dose-escalation trial of a neutralizing human monoclonal anti-CTLA-4 antibody (ipilimumab) in patients with RM following allo-HCT. Eligibility criteria included allo-HCT ≥90 days previously, &gt; 50% donor T-cell chimerism, no prior grade 3/4 GVHD, no prophylaxis/therapy for GVHD for ≥ 6 weeks. Patients received a single dose of ipilimumab over 90 min. (Donor lymphocyte infusion (DLI) at a dose of 5 x 10e6 CD3 cells/kg was allowed 8 weeks following ipilimumab if no GVHD occurred and malignancy was present. Seventeen patients (13M, 4F; median age 42 (21–64); Hodgkin’s disease [HD] =7 Myeloma [MM]=3, CML=2, CLL=1, AML=1, NHL=1, Renal Ca =1, Breast Ca=1; 14 related donors, 3 unrelated; 5 myeloablative, 12 RICT) were treated at three centers (4 at dose-level 1 [DL1] 0.1 mg/kg, 3 at 0.33 mg/kg [DL2], 4 at 0.66 mg/kg [DL3], 3 at 1.0 mg/kg [DL4] and 3 at 3.0 mg/kg [DL5]). Six patients had failed prior DLI. Median time between BMT and ipilimumab was 374 d (125–2368). Seven patients received additional DLI. Ipilimumab was well tolerated in this setting. No DLT was seen at levels up to DL5. No infusional toxicity was seen. No patient developed clinically significant GVHD within 90 days following ipilimumab. One patient developed grade II acute GVHD of the skin 12 weeks following DLI. Two possible immune breakthrough events were documented: grade 3 polyarthropathy 14 weeks following ipilimumab, but also 6 weeks post DLI, which resolved with corticosteroid therapy, (AML, DL1, RhF+ pre- ipilimumab); grade 1 chemical hyperthyroidism with thyroid-stimulating antibody 6 weeks post ipilimumab (CLL, DL3). Two patients developed objective evidence of disease response after ipilimumab alone: regression of refractory lymphadenopathy in a patient with mantle cell NHL lasting 3m [DL4]; CR in a patient with HD ongoing at 2m [DL5].Both patients had failed prior DLI. Two additional patients demonstrated possible anti-cancer effects (reduction of PB and BM blasts in AML, DL1; maintenance of molecular remission in a CML patient given ipilimumab alone for 2.5 yrs despite stopping imatinib, DL1). PK data will be presented. This study shows that clinically active doses of ipilimumab (up to 3.0 mg/kg) can safely be administered to patients with RM following allo-HCT without inducing/exacerbating GVHD. Organ specific immune breakthrough events can be seen as in non-allo-HCT patients.

The Impact of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with Recurring Hodgkin’s Lymphoma: An EBMT Study on 151 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3061-3061 ◽  
Author(s):  
Alexander Claviez ◽  
Carmen Canals ◽  
Marc Boogaerts ◽  
Jerry Stein ◽  
Stephen Mackinnon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
The Impact ◽  
Time Point

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for patients with recurring Hodgkin’s lymphoma (HL). Standardized inclusion criteria, the optimal time point and the type of conditioning regimen have, however, not been clarified yet. Moreover, high treatment related mortality (TRM) has hampered the widespread use of this procedure. Only few data are available on the impact of allogeneic HSCT in pediatric and adolescent patients. Patients and Methods: We analyzed patients registered in the EBMT Lymphoma Database (age < 21 years at transplantation) who received an allogeneic HSCT for relapsed or refractory HL between 1987 and 2005. Results: A total of 151 patients (56% male) were included. Median age at diagnosis and HSCT was 15 and 18 years, respectively. 57% of patients had received three or more lines of treatment prior to allogeneic HSCT including autologous HSCT in 77 patients with a median interval of 18 months between autologous and allogeneic HSCT. The majority of donors were matched related (63%), followed by matched unrelated (25%) and mismatched donors. A full myeloablative conditioning regimen was given to 40% of patients and 60% received a regimen of reduced intensity. Disease status at HSCT was sensitive (complete or partial remission) in 59% and refractory (no change or progression) in 41%. 23% of the patients developed grade 2–4 acute graft versus host disease (GvHD). Of 35 patients with evaluable chronic GvHD, limited and extensive GvHD were balanced. With a median follow-up of 25 months (maximum 154), 75 patients (50%) are alive and 59 of them disease-free. 56 patients (37%) relapsed after a median time of 5 months (<1 to 36 months) and only 16 were alive at last contact. The probability for progression-free survival (PFS) at 2 and 5 years were 39% and 29% respectively. The cumulative incidences (CI) for relapse at 1, 2 and 5 years were 29%, 37% and 44%, respectively, whereas the CI for TRM at 1, 2 and 5 years were 20%, 24% and 27%, respectively. In multivariate analysis, HLA disparity (p=.002), HSCT before 2001 (p=.01) and female sex (p=.02) were associated with a higher TRM, while poor performance status (p=.005) and refractory disease (p=.04) resulted in an inferior PFS. Reduced treatment intensity had no impact on relapse rate within one year after HSCT but was associated with a higher incidence of relapse (p=.02) beyond 12 months. The PFS and TRM of patients without adverse prognostic factors (HSCT >2001, matched donors and good performance status at HSCT) at 1, 2 and 5 years was 67%, 50% and 43%, and 11%, 17% and 17%, respectively. Conclusion: This study of young patients with HL receiving allogeneic HSCT indicates a comparable outcome to adult patients. Transplantation was beneficial especially for patients with a good performance status, HSCT in recent years and available matched donors. Allogeneic HSCT should be carefully selected at an early time point in children failing standardized primary and salvage treatment.

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.

Intravenous Busulfan-Based Myeloablative Conditioning Is Comparable to TBI-Based Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Recipients with Acute Myeloid Leukemia: A Nationwide Retrospective Study From the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1922-1922
Author(s):  
Takuya Yamashita ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
Kazuteru Ohashi ◽  
Saiko Kurosawa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Conditioning Regimens ◽  
Acute Myeloid

Abstract Abstract 1922 In allogeneic hematopoietic stem cell transplantation (HSCT) for recipients with acute myeloid leukemia (AML), cyclophosphamide (Cy) combined with total body irradiation (TBI) (Cy+TBI) is the most common myeloablative conditioning (MAC) regimen, but busulfan (Bu) in combination with Cy (Bu+Cy) has been an alternative to Cy+TBI since early 1980s. But as oral Bu has a problem of interpatient variation in intestinal absorption, intravenous Bu (ivBu) has been developed and substituted for Bu in conditioning regimens for HSCT. For the last decade, fludarabine (Flu)-based regimens with the addition of cytotoxic agents such as Bu or melphalan (L-PAM) have been developed as reduced-intensity conditioning (RIC) regimens. After the introduction of ivBu, Flu+ivBu has become one of the common RIC regimens. In Japan, ivBu was introduced in 2006 and have been widely used as a part of conditioning regimens. In this nationwide retrospective study, we evaluated the clinical outcomes of allogeneic HSCT for AML, especially focusing on ivBu-based conditioning regimens. The study population included HSCT recipients reported to the Japan Society for Hematopoietic Cell Transplantation. From this database, we extracted the data of adult patients with AML who received first allogeneic HSCT between 1975 and 2010. There were 9,396 recipients selected according to this criterion. Then, we excluded 345 (3.7%) cases from the study because of missing key variables. A total of 9,051 recipients were evaluated in this study. Median age at transplant was 43 years (range, 16–82), and 41.8% (n=3,785) were female. Types of transplant included bone marrow transplantation from sibling donor (RBMT) (n=1,978, 21.9%), peripheral blood stem cell transplantation from sibling donor (RPBSCT) (n=1,411, 15.6%), bone marrow transplantation from unrelated donor (UBMT) (n=3,321, 36.7%) and cord blood transplantation from unrelated donor (CBT) (n=1,728, 19.1%). MAC regimens were applied to 80.2% (n=7,259) of recipients and RIC regimens to 19.8% (n=1,792), according to the definitions proposed by the NMDP and the CIBMTR in 2007. These MAC regimens included Bu+Cy-based (12.4% of all MAC regimens), Cy+TBI-based (50.0%) and ivBu+Cy-based (5.6%) regimens. RIC regimens consisted mainly of Flu+Bu-based (27.6% of all RIC regimens), Flu+L-PAM-based (24.1%) and Flu+ivBu-based (19.5%) regimens. Median follow-up of survivors was 1,437 days (range, 26–8,344). In MAC setting, overall survival (OS) of HSCT recipients with ivBu+Cy-based regimens did not show the significant difference between that with Bu+Cy or Cy+TBI-based ones in RBMT (p=0.168), RPBSCT (p=0.236) and UBMT (p=0.604). But in CBT, Cy+TBI was significantly superior to Bu+Cy (p=0.004). Though the cumulative incidences of relapse (RI) were similar among recipients with these three regimens, the cumulative incidence of non-relapse mortality (NRM) with Bu+Cy was significantly higher than with Cy+TBI in CBT (p=0.049). In RIC setting, OS of recipients with Flu+ivBu-based regimens was comparable to that with Flu+Bu or Flu+L-PAM-based ones regardless of the type of transplant. RIs with these three regimens were almost equivalent, but NRM with Flu+ivBu-based was significantly lower than that with Flu+L-PAM-based in UBMT (p=0.023). In the multivariate analysis for OS, ivBu+Cy-based regimens did not have significant impacts regardless of the type of transplant, but Flu+ivBu-based regimen had a significantly favorable impact in RBMT (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.23–0.99). In the multivariate analysis for NRM, Flu+ivBu-based regimen had a significantly reduced risk compared with Flu+L-PAM in RBMT (HR 0.32, 95%CI 0.11–0.95) and UBMT (HR 0.46, 95%CI 0.25–0.83). These data indicates that ivBu+Cy-based and Cy+TBI-based MAC regimens have almost equivalent efficacy profiles for OS, RI and NRM, and Flu+ivBu-based RIC regimens can reduce the risk of NRM compared with Flu+Bu and Flu+L-PAM-based ones in allogeneic HSCT for recipients with AML. Disclosures: No relevant conflicts of interest to declare.

The Use of Imatinib with Chemotherapy and Allogeneic Hematopoietic Stem Cell Transplantation Improves Survival of Philadelphia Positive Acute Lymphoblastic Leukemia in Adults

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3653-3653
Author(s):  
Josefina Perez-Nuñez ◽  
Antonio Jimenez-Velasco ◽  
Katy Hurst ◽  
Manuel Barrios-Garcia ◽  
MJ Moreno ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Philadelphia positive acute lymphoblastic leukemia (Ph + ALL) accounts for approximately 20% -30% of all adult ALL. The prognosis of patients with Phi + ALL is unfavorable when treated with standard chemotherapy schemes, presenting a long-term survival of 15% -20%. Since the introduction of Imatinib (IM) to treatment regimens the survival of these patients has improved, although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option. We conducted a retrospective analysis of Ph + ALL patients before and after IM became available in order to analyze the impact of IM on survival in adult Phi + ALL. Patients and methods Between April 1997 and April 2013 we diagnosed 120 over 15 year old patients with ALL (B and T lineage), 31 (25.8%) of which were Phi +, all B lineage. Of these 31 cases, 30 were treated with protocols from Spanish group PETHEMA with curative intent. 14 of them (47%) were treated with chemotherapy and Imatinib (IM cohort) and 16 (53%) with chemotherapy (pre-IM cohort). In 17 of the 30 cases allogeneic HSCT was performed, 7 in the pre-IM cohort and 10 in the IM cohort. In the post-transplant period, two patients were treated with Dasatinib due to positive minimal residual disease (BCR-ABL1 positive). The probabilities of overall survival (OS) (death) and event free survival (EFS) (no response, relapse or death) were estimated using the Kaplan-Meier product limit method. Differences between groups were tested using the X2 test. Univariate analysis was performed using Cox regression models or log-rank test. Multivariate analysis was performed using Cox proportional hazards regression model. The study was conducted in accordance with the Declaration of Helsinki. Results The median age was 38 years (range, 15-66 years), 17 patients were males and 13 females. The whole series survival was 32.4 ± 9.2%. The OS mean of the pre-IM cohort was 3.1 years (CI 95%, 0.5-5.7) and 6.9 years (CI 95%, 4.4-9.4) in the IM cohort (figure 1). The main characteristics of both groups are reflected in Table 1. When we analyzed the EFS, the variables that influenced it were being treated with IM (48% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.03), having received an allogeneic HSCT (45% versus 8%, p = 0.004) and being in first complete remission before allogeneic HSCT (51% versus 0%, p <0.001). In the analysis of OS, the only variables with prognostic significance were: treatment with IM (63% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.01) and having received an allogeneic HSCT (55 % versus 0%, p <0.001). When the 17 patients that received allogeneic HSCT were analyzed separately, OS in the pre-IM cohort was 29 ± 17% versus 79 ± 13% in the IM cohort (p = 0.057). Table 1. Patient characteristics (N=30) Characteristic Pre-IM cohort(N=16) IM cohort(N=14) P Female/Male 7/9 6/8 0.96 Age ² 40 years 12 (75%) 10 (71%) 0.82 ³ 50 x109/L WBC 8 (50%) 4 (29%) 0.23 Transcript type: e1a2 b2a2/b3a2 12 (75%) 4 (25%) 11 (79%) 3 (21) 0.83 Morphological CR after induction 13/15 (88%) 13/13 (100%) 0.17 No. of Allo-HSCT 7 (44%) 10 (71%) 0.13 CR pre Allo-HSCT: 1CR 2CR 5 (71%) 2 (29%) 10 (100%) 0 (0%) 0.07 Relapse 8/13 (61.5%) 4/13 (31%) 0.12 Exitus 14 (87.5%) 5 (36%) 0.003 Abbreviations: IM, imatinib. WBC, white blood cells. CR, complete remision. Allo-HSCT, allogenetic hematopoietic stem cell transplantation. Figure 1 Figure 1. Conclusions In our study we show how adult Phi + ALL patients who are treated with chemotherapy associated with IM and subsequently receive an allogeneic HSCT exhibit a higher overall survival rate than those treated in the pre-IM era. Although Phi + ALL is still considered of very high risk, in our series of patients treated in the IM era, with a follow-up of over 7 years, overall survival was of 63%, higher than that of historical series of adults with Phi negative ALL. This work has been financed by a grant from the Malaga Association for Research in Leukemia "AMPILE" and the FIS 11-01966 project. Disclosures No relevant conflicts of interest to declare.

Mesenchymal Stromal Cells as an Adjuvant Treatment for Severe Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

2014 ◽  
Vol 133 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Ying Wang ◽  
Feng Chen ◽  
Bing Gu ◽  
Guanghua Chen ◽  
Huirong Chang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Stromal Cells ◽  
Late Onset ◽  
Hemorrhagic Cystitis ◽  
Gross Hematuria ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

The management of severe late-onset hemorrhagic cystitis (LO-HC) after allogeneic hematopoietic stem cell transplantation (HSCT) is still challenging. Because mesenchymal stromal cells (MSCs) possess anti-inflammatory and tissue repair-promoting properties, we retrospectively analyzed the efficacy and safety of MSC infusions in 7 of 33 patients with severe LO-HC after allogeneic HSCT. During treatment, each patient received at least one MSC infusion of Wharton's jelly derived from the umbilical cord of a third-party donor. In 6 patients, MSC treatment was initiated within 3 days of gross hematuria onset, while the 7th patient received an infusion 40 days later. The median dose was 1.0 (0.8-1.6) × 106/kg. Five of 7 patients responded to treatment. Notably, gross hematuria promptly disappeared in 3 patients after 1 infusion, with a time to remission not seen in patients without MSC infusion. Two patients showed no response even after several infusions. No acute or late complications were recorded. Our findings indicate that MSC transfusion might be a feasible and safe supplemental therapy for patients with severe LO-HC after allogeneic HSCT.

Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4367-4371 ◽  
Author(s):  
Mark J. DiNubile ◽  
Thomas P. Stossel ◽  
Olof C. Ljunghusen ◽  
James L. M. Ferrara ◽  
Joseph H. Antin
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Physiological Role ◽  
Actin Binding ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Plasma Gelsolin ◽  
Novel Strategy

The idiopathic pneumonia syndrome (IPS) represents a common and often fatal complication of hematopoietic stem cell transplantation (HSCT). Gelsolin is a highly conserved actin-binding protein normally present in plasma that may serve a basic physiological role in limiting acute lung injury of diverse etiologies. We hypothesized that depletion of circulating gelsolin following HSCT might play a permissive role in the pathogenesis of IPS. Plasma gelsolin levels were measured by immunoblotting in frozen samples obtained weekly from 24 patients undergoing allogeneic HSCT. Patients with and without IPS were similar with respect to age, diagnosis, histocompatibility differences between donor and recipient, and conditioning regimen. Mean gelsolin levels in the 9 patients with rapidly fatal IPS were significantly lower than those in patients without this complication by week 3 after HSCT (101 ± 61 mg/L versus 221 ± 54 mg/L; P = .0002). Seven (88%) of the 8 patients with gelsolin levels of less than 100 mg/L in the first month after HSCT died from IPS within 3 months; conversely, gelsolin levels fell to less than 100 mg/L in 7 (78%) of the 9 patients who died from IPS within 3 months of HSCT (P = .0007). These findings suggest that gelsolin levels shortly after allogeneic HSCT can predict the later development of fatal IPS. Gelsolin replacement in selected transplant patients may offer a novel strategy to prevent or reverse IPS.

scholarly journals Effect of Donor KIR2DL1 Allelic Polymorphism on the Outcome of Pediatric Allogeneic Hematopoietic Stem-Cell Transplantation

2013 ◽  
Vol 31 (30) ◽  
pp. 3782-3790 ◽  
Author(s):  
Rafijul Bari ◽  
Piya Rujkijyanont ◽  
Erin Sullivan ◽  
Guolian Kang ◽  
Victoria Turner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Allelic Polymorphism ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Donor Graft

Purpose Killer-cell immunoglobulin-like receptors (KIRs) that regulate natural-killer cells are highly polymorphic. Some KIR2DL1 alleles encode receptors that have stronger signaling function than others. We tested the hypothesis that the clinical outcomes of allogeneic hematopoietic stem-cell transplantation (HSCT) could be affected by donor KIR2DL1 polymorphism. Patients and Methods All 313 pediatric patients received allogeneic HSCT at a single institution. Donor KIR2DL1 functional allele typing was retrospectively performed using single nucleotide polymorphism assay. Results Patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R245) had better survival (P = .0004) and lower cumulative incidence of disease progression (P = .001) than those patients who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C245). The effect of KIR2DL1 allelic polymorphism was similar in patients with acute myeloid leukemia or acute lymphoblastic leukemia among all allele groups (P ≥ .71). Patients who received a KIR2DL1-R245–positive graft with HLA-C receptor-ligand mismatch had the best survival (P = .00003) and lowest risk of leukemia progression (P = .0005) compared with those who received a KIR2DL1-C245 homozygous graft. Conclusion Donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection.

scholarly journals Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Suk-young Lee ◽  
Naoki Kurita ◽  
Koichiro Maie ◽  
Masanori Seki ◽  
Yasuhisa Yokoyama ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myeloid

Although hematopoietic stem cell transplantation (HSCT) has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML), there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT) using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.

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