Impact of CD3/T Regs Ratio in Donor Graft On Survival Rates in Allogeneic Peripheral Blood Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2030-2030
Author(s):  
Mario Delia ◽  
Domenico Pastore ◽  
Anna Mestice ◽  
Paola Carluccio ◽  
Tommasina Perrone ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Survival Rates ◽  
Significant Difference ◽  
Donor Graft ◽  
The Impact

Abstract Abstract 2030 Background: The therapeutic efficacy of allogeneic stem cell transplantation (alloSCT) for hematological malignancies relies largely on the graft versus leukemia (GvL) effect exerted by the donor CD3 cells, but an uncontrolled graft-versus-host-disease (GvHD) bears a risk of complications. On the other hand, T regs cells (CD4+CD25high Foxp3+) are believed to maintain tolerance and to inhibit GvHD after alloSCT; also, the Foxp3 gene encodes a transcription factor that is a key for thymic development, so T regs cells could preserve an optimal microenviroment for the reconstitution of functional immunity after alloSCT. Moreover, when looking at post allotransplant patients' outcomes, while it is largely known the impact of acute GVHD (triggered by CD3 donor T cells) on survival, there is no evidence that donor graft CD3/T regs ratio may determine an effect in terms of OS, NRM and relapse free survival rates so far. Patients and Methods: In this study we analyzed the graft CD3+/Tregs ratio (gCD3/Tregs R) and determined its impact on acute GVHD (aGVHD), immunological recovery and survival rates (OS, NRM and Relapse) after myeloablative alloPBSCT. We analyzed 74 consecutive patients transplanted with unmanipulated peripheral blood stem cells from an HLA identical related donor (n=48) or an HLA identical unrelated donor (n=26); diagnoses were acute myeloid leukaemia (n=62), acute lymphoblastic leukaemia (n=13). The median CD3+ and Tregs dose administered was 238 (range (r): 67–550) and 12,5×106̂/Kg (r: 2–21), respectively; the median gCD3/Tregs R was 19 (r: 8–250). Patients were subdivided into a high gCD3/Tregs R (>=36) group (HR group n= 30) and a low gCD3/Tregs R (<36) (LR group n=44). Results: The incidence of aGVHD (grade II-IV) in the low gCD3/Tregs R (LR) group was lower than in the high gCD3/Tregs R (HR) group (4/30 or 13% vs 36/44 or 82%, p<.001). The OS, NRM and relapse rate at 3 years was 54,29 and 34%, respectively. Comparing LR with HR group a statistically significant difference is demonstrated for OS and NRM rates (65 vs 31%,p<.004; 3 vs 71%, p<.001), respectively, but not for the R one (35 vs 30%, p=ns). Comparing aGVHD+ with aGVHD- group OS, NRM and relapse were always statistically significant different (39 vs 65%,p<.005; 61 vs 7%,p<.001; 9 vs 53%,p<.002). Conclusions: Taken together, our data may suggest that Tregs content is able to mediate protective effects against aGVHD, while preserving GvL effects as demonstrated by relapse rate comparison between H and LR groups. However, larger studies are needed to understand the real contribution of gCD3/Tregs R on survival rates. Disclosures: No relevant conflicts of interest to declare.

Improved Immune Reconstitution Following Pre-Emptive CD8-Depleted Donor Lymphocyte Infusions (DLIs) after Haploidentical Stem Cell Transplantation (SCT) Using a Reduced-Intensity Conditioning (RIC) Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2908-2908
Author(s):  
Paolo Corradini ◽  
Anna Raganato ◽  
Matteo Carrabba ◽  
Lorenza Gandola ◽  
Claudia Lombardo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Total Dose ◽  
Cell Transplantation ◽  
Immune Reconstitution ◽  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Immune Recovery ◽  
Grade Ii ◽  
The Impact

Abstract Allogeneic stem cell transplantation (SCT) from an haploidentical family donor has been reported as a viable option in acute leukemias when matched donors are unavailable. However, the extensive T-cell depletion (TCD), required to prevent graft-versus-host disease (GVHD), is associated to delayed immune recovery and high transplant-related mortality. In an ongoing phase I–II trial for patients (pts) with advanced hematological malignancies, we combined a RIC regimen, including thiotepa (10 mg/kg), fludarabine (120 mg/ms), cyclophosphamide (60 mg/kg) and TBI (2 Gy), with pre-emptive administration of CD8-depleted DLIs (starting from 1x104 up to 1x105 cells/kg). Ex-vivo and in-vivo TCD were carried out by CD34+ cell selection using the CliniMACS device and alemtuzumab (30 mg day −2), respectively. The aim of the study was to investigate in a dose finding study the safety and the impact on immune-reconstitution of CD8-depleted DLIs. Six-teen pts with hematological malignancies (n=14 NHL/HD, n=1 ALL, n=1 AML) were included, median age was 35 years (range, 15–65), 10 (63%) were chemorefractory, and 68% and 75% had failed a previous auto or at least 3 CT lines, respectively. Pts received a median of 10.6 x106/Kg CD34+ and 1x104/kg CD3+. All pts engrafted with full donor chimerism from day +30. At a median follow-up of 9 months, 12 pts were alive and 4 died (n=1 infection, n=3 disease). The estimated OS at 2 years was 58%; 7 of 16 (44%) relapsed at median time of 100 days after SCT. CD8-depletion of 14 donor lymphocyte aphereses was performed with a new depletion protocol (Clinimacs CD8-Microbeads) that reduces the content of CD8+ cells by at least 3 logs. The median CD3+, CD4+, CD56+/CD3+, CD20+ cell recovery were 62% (range, 35–91%), 88% (63–128%), 51% (8–78%), 76% (33–128%), respectively. Before DLIs, only 1 of 16 pts (6%) developed de novo acute GVHD (grade II). A total of 22 CD8-depleted DLIs were administered to 9 of 16 pts without any engraftment problem. The first cohort of pts (n=5) received a total dose of 3–6x104/kg CD8depleted DLIs starting at day +45 divided in 3 monthly infusions: none of them developed aGVHD. Given no toxicity, we escalated doses and the second cohort (n=4) received a total dose of 10–25x104/kg CD8-depleted DLIs divided in 3 monthly infusions: 3 pts had acute GVHD (grade II). Overall, the incidence of acute GVHD was higher (75% vs 0%, P&lt;0.04) in pts receving larger numbers of donor cells. Interestingly, the median values of CD4+/ul and CD8+/ul were 98 (range, 8–612) and 150 (range, 15–988) at 4 months; 247 (range, 55–333) and 235 (range, 3–1000) at 5 months after SCT. The median value of CD19+/ul cells were 134 (range, 0–292) and 160 (range, 0–256) at 4 and 5 months, respectively. NK cells remained between the value of 394/ul and 569/ul in the first 6 months after SCT. Our results suggest that: (1) haploidentical SCT with RIC regimen is feasible with a high rate of engraftment and a low acute GVHD incidence; (2) pre-emptive CD8-depleted DLIs are feasible without GVHD until the total dose of 6 x104/kg; 3) higher doses can induce acute GVHD, but no grade III–IV was observed; 4) despite the limited number of pts, we observed a faster immune recovery and a relatively low mortality rate for infections.

Prognostic Impact of the Detection of the WT1 Gene mRNA with Peripheral Blood in Adult Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3289-3289
Author(s):  
Shuichi Miyawaki ◽  
Nahoko Hatsumi ◽  
Toshiharu Tamaki ◽  
Tomoki Naoe ◽  
Keiya Ozawa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Consolidation Therapy

Abstract Background: Approximately 70–80% of all newly diagnosed patients with adult AML achieve a complete remission (CR). However, only about one third of those pts remain free of disease for more than 5 years. It is therefore important to predict which pts are most likely to suffer a relapse and thus perform alternative treatments such as stem cell transplantation in order to improve the prognosis of AML. We evaluated the impact of the detection of Wilms’ tumor gene1 (WT1) mRNA in the peripheral blood on the prognosis of AML pts. Patients and Methods: From June 1, 2001 to October 30, 2003 a study was performed on 191 pts with AML which evaluated the clinical usefulness of a WT1 mRNA assay kit for the early detection of relapse in AML pts (submitted in Rinsho Ketsueki). From these 191 pts, we selected the subjects for this study. All selected subjects achieved a complete remission, and also had their WT1 expression analyzed after consolidation therapy. The pts were excluded if they had received a stem cell transplantation before relapse. The WT1 mRNA levels were determined using the WT1 mRNA assay kit (Otsuka Pharmaceutical Co. Ltd) in accordance with the standard operating procedures using peripheral blood. The lower limit of detection was 50 copy/μgRNA. Therefore, less than 50 copy/μgRNA was judged as negative. All induction, consolidation and maintenance therapies were performed according to institutional standards. Results: Of 118 pts who achieved a complete remission, 50 pts (median age: 56 yrs 22–86) were evaluable. Their median WT1 mRNA levels before induction therapy was 48327 copy/μgRNA (137–329185). The WT1 mRNA levels at diagnosis did not correlate with either the relapse rate, DFS or OS, respectively. After CR, the WT1 mRNA level ranged from &lt;50 copy/μg to 30732 copy/μgRNA. Thirty-four (69.4%) pts were positive and 15 pts (30.6%) were negative for the WT1 mRNA. The relapse rate of the positive pts and of the negative pts was 73.5% and 40.0% (P=0.0248 sensitivity=80.6 % specificity=50.0%), respectively. The OS rate at 3 years was 53.1% in the positive pts and 79.0% in the negative pts (P=0.1227), respectively. The DFS rate at 3 years was 30.0% in the positive pts and 60.0 % in the negative pts (P=0.0906), respectively. After consolidation therapy, the WT1 mRNA level ranged from &lt;50 copy/μgRNA to 49174 copy/μgRNA. The WT1 positive pts numbered only 15 pts (32.6%) and the negative pts numbered 31 (67.4%). The relapse rate of the positive pts and the negative pts was 80.0% and 54.8% (P=0.0974), respectively. The OS of rate at 3 years was 42.8% in the positive pts and 69.8% in the negative pts (P=0.0381), respectively. The DFS rate at 3 years was 20.0% in the positive pts and 50.0% in the negative pts (P=0.0116). The rate of relapse within 1 year was 73.3% in the positive pts and only 33.3% in the negative pts (P= 0.0116). Conclusion: This study shows that the detection of the WT1 mRNA in the peripheral blood after treatment closely correlated with the prognosis in AML.

Impact of the New Anti-Myeloma Drugs on Outcome of Allogeneic Stem-Cell Transplantation with Reduced-Intensity Conditioning in Patients with High-Risk Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4456-4456
Author(s):  
Jean El-Cheikh ◽  
Roberto Crocchiolo ◽  
Jean Marie Boher ◽  
Sabine Furst ◽  
Anne Marie Stoppa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Graft Versus Host ◽  
Significant Difference ◽  
The Impact ◽  
Reduced Intensity

Abstract Abstract 4456 The increasing use of the novel agents, lenalinomide and bortezomib, in the treatment of multiple myeloma (MM) has contributed to higher complete remission (CR) rates and longer overall (OS) and event free survival (EFS). We assessed the impact of these drugs on the outcome of high-risk MM patients treated with allogeneic stem-cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) over the last 10 years in our program. This retrospective study compared 45 patients (group1) transplanted in our centre between January 1999 and January 2006 and who had not received either novel agent prior to transplant (as induction or relapse therapy) with 34 patients (group 2) transplanted between January 2006 and June 2010 who received either one or both drugs before allo-SCT. The median time between diagnosis and Allo-SCT was 37 months (6–161) and 41 months (9–145) in the two groups respectively (p=NS). The median time between auto-SCT and allo-SCT was 9 months (2–89) and 27 months (2–49) respectively (p<0.0001). 36 patients (80%) in the first group vs. 8 patients (24%) in the second group received a tandem auto allo-SCT (p<0.0001). The disease status at transplantation was in CR in 2 patients (4%) vs. 10 patients (29%) and PR or stable disease in 35 patients (78%) vs. 21 patients (62%) in the first and the second group respectively (p<0.0033). in the table 1 we resumed some important data. Table 1Table 1:Patients Characteristic:Characteristics n=791999-2006 n=45 (57%)2006-2010 n=34 (43%)Fisher, p valueMedian age years (range)51 (27-65)55 (39-67)Number of prior therapies 1 2318 (40) 17 (38) 10 (22)8 (24) 18 (52) 8 (24)0.1509Cytogenetics at diagnosis Normal Del(13) Del (17) t (4;14) NA5 (11) 4 (9) 36 (80)3 (9) 12 (35) 19 (56)0.00504Disease status CR ou VGPR PR ou SD PD or refractory2 (4) 35 (78) 8 (18)10 (29) 21 (62) 3 (9)0.003359Donor type Matched Sibling Unrelated Donor45 (100) 021 (62) 13 (38)0.0004517Conditioning treatment With TBI With ATG19 (42) 26 (58)9 (26) 25 (74)0.1632Legend: Allo-SCT, allogeneic stem cell transplantation; Auto-SCT, autologous stem cell transplantation; CR, complete response; VGPR, very good partial response; PR, partial response; SD, stable disease; PD, progressive disease. GVHD indicates graft-versus-host disease; CSP, cyclosporine; MMF, mycofenolate mofetyl; TBI, total-body irradiation; ATG, anti-thymoglobulin; TRM, Transplant related mortality. Groups differ in several aspects: In recent years allogeneic transplant was considered rather as salvage therapy in patients relapsing after auto-SCT than in a tandem auto-allo strategy, patients with cytogenetic aberrations (p<0.005), and stem cell source from unrelated donor (13 patients (38%) vs. none) (p<0.0004), and two days of anti-thymoglobuline (ATG 2,5mg/kg/day). (P<0.001), in the second group. Table 1 The median follow-up after transplant was 45 (2–127) and 16 (3–39) months in the first and second group respectively (p<0.001). The cumulative incidence of acute graft versus-host disease (GVHD) tended to be higher before 2006 (47% vs. 24%; p=0.0584). The cumulative incidence of chronic GVHD was statistically different (56% vs. 30%; p=0.0241). The estimated probability of TRM at day 100 was 12% in the first group vs. 0 % in the second group (p=0.077) and did not differ between groups at 2 years. (18% vs. 23% (p =0.537)). The overall survival (OS) at two years was 60% vs 70% in the first and second group respectively (p=0.1784). The progression-free survival (PFS) tended to be different at 2 years (45% vs. 65% (p=0.056)). The median of PFS is 22 months for patients transplanted prior 2006 and is not reached in the second group (p=0.1811). In our study there was no significant difference in OS or TRM between the 2 groups in multivariate analysis; only the number of previous auto-SCT with more than two high dose chemotherapies has a negative impact on the OS. There was a significant difference in the incidence of relapse between the 2 groups in the multivariate analysis. Although we cannot carry out the impact of other changes related to our practice in the same period, these data suggests an impact in transplant outcomes of novel drugs introduced in the therapy of MM (lower TRM, GVHD and higher disease control). This piece of information, if confirmed, should be taken into considerations for present and future approaches. Disclosures: No relevant conflicts of interest to declare.

Impact of Early Blast Clearance Following Induction Chemotherapy On the Outcome of Patients with Acute Myelod Leukemia Undergoing Allogeneic Stem Cell Transplantation in First Complete Remission

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1998-1998
Author(s):  
Philipp G. Hemmati ◽  
Theis H. Terwey ◽  
Philipp le Coutre ◽  
Gero Massenkeil ◽  
Bernd Dörken ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Allogeneic Stem Cell Transplantation ◽  
High Dose ◽  
Significant Difference ◽  
The Impact ◽  
First Complete Remission

Abstract Abstract 1998 Purpose: In patients with newly diagnosed acute myeloid leukemia (AML) rapid achievement of remission by induction chemotherapy is an important predictor for long-term disease control. In turn, patients who fail to attain early blast clearance after the first chemotherapy course have an inferior outcome. Here, we investigated the impact of early blast clearance on the overall outcome of patients with AML undergoing allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1) as consolidation therapy. Patients and Methods: 169 (90 female, 79 male) patients with AML who underwent alloSCT in CR1 at our center between 1994 and 2011 were included. Data were prospectively recorded in our transplant data base and retrospectively analyzed as of December 31st, 2011. In detail, 107 patients (64%) had de novo AML, 31 patients (18%) had AML evolving from myelodysplastic syndrome (MDS), and 31 patients (18%) had therapy-related AML. According to the criteria of the SWOG/ECOG, cytogenetic risk was either favorable (6 patients, 4%), intermediate (104 patients, 62%), or poor (47 patients, 27%). Prior to alloSCT all patients were treated in a German multicenter AML trial and received at least two courses of induction chemotherapy, i.e. either standard “7+3” (daunorubicin 60 mg/m2, day 3–5 and Ara-C 100 mg/m2, day 1–7) or a “high-dose Ara-C” containing regimen (Ara-C 1–3 g/m2). In 98 patients (58%) induction chemotherapy resulted in blast clearance after the first course, whereas 71 patients (42%) failed to achieve early remission, but entered remission after 1 or 2 subsequent courses. Median age at transplantation was 47 years (range: 17–69 years). In 146 patients (86%) alloSCT was performed using peripheral blood stem cells (PBSCs), whereas 23 patients (14%) received a bone marrow (BM) graft. Conditioning consisted of standard myeloablative conditioning (MAC: 6 × 2 Gy TBI and 2 × 60 mg/m2 cyclophosphamide) in 81 patients (48%), whereas 86 patients (52%) received reduced intensity conditioning (RIC: busulfan 2 × 4 mg/kg, fludarabine 6 × 30 mg/m2 and ATG 4 × 10 mg/kg). A matched related donor was available in 82 patients (49%), whereas 68 patients (40%) or 19 patients (11%) were transplanted from a matched-unrelated or mismatched unrelated donor. Results: After a median follow-up of 45 months (range: 3–196 months) for the surviving patients, 91 patients (54%) are alive and in continuous remission. Causes of death were relapse in 38 patients (22%) or NRM in 33 patients (19%). At 1, 3 or 5 years projected overall survival (OS) was 72±6%, 58±6%, or 54±8% for all patients. Probability of relapse or non-relapse mortality (NRM) at 1, 3, and 5 years was 20±10% (20±11%), 31±12% (20±11%), and 34±12% (20±11%). Although there was no statistically significant difference in OS at 3 and 5 years between patients who achieved early blast clearance as compared to patients who failed to do so (p=0.09), disease-free survival (DFS) and probability of relapse differed significantly between the two groups at 3 years (77±8% vs 55±14%) or 5 years (75%±9% vs 52%±14%) following alloSCT (p=0.02). There was no significant difference in NRM between the two subgroups. Likewise, there was no statistically significant difference between patients conditioned with either MAC or RIC. In multivariate analysis cytogenetic risk group and remission status were identified as independent prognostic factors for DFS and probability of relapse. Conclusions: These results suggest that in patients with AML undergoing alloSCT in CR1 early blast clearance, i.e. following the first course of induction chemotherapy, predicts a very favorable outcome. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of Age in Allogeneic Stem Cell Transplantation with Thiotepa Busulfan and Fludarabine (TBF) for Myelofibrosis : A Retrospective Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4858-4858
Author(s):  
Federica SORA ◽  
Patrizia Chiusolo ◽  
Sabrina Giammarco ◽  
Idanna Innocenti ◽  
Francesco Autore ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Total Dose ◽  
Cell Transplantation ◽  
Older Patients ◽  
Research Funding ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) currently remains the only curative therapy for intermediate or high risk disease.myelofibrosis (MF). We are reporting 56 patients (pts) who underwent an allogeneic HSCT in our Centre between 2016 and 2020, and assessed factors predictive of outcome. The median age was 59 years (36-72). Most patients (72%) were JAK2+ and had int2-high DIPSS (92%). The conditioning regimen consisted of thiotepa, busulfan , fludarabine (TBF). All pts received thiotepa 10 mg/kg and fludarabine 150 mg/m^2. The dose of busulfan was adjusted considering the age and the comorbidity score. One pt received 3 days of busulfan (total dose 9.6 mg/kg); 47 received 2 days (total dose 6.4 mg/kg) and 8 received one day of busulfan iv (3.2 mg/kg). Donor was an identical sibling in 13 pt, haploidentical in 18, matched unrelated donor (UD) in 18 and a mismatchedUD in 7. Thus we had 31 HLA matched and 25 HLA mismatched grafts. Fortytwo patients received post-transplant cyclophosphamide (PTCy)-based GVHD (Graft versus host disease ) prophylaxis with cyclosporine and mycophenolate mofetil , and 14 patients received a standard GvHD prophylaxis (CSA+MTX+ATG). The 2 year survival (OS) was 73 % and disease free survival (DFS) was 66 % and the cumulative incidence (CI) of TRM was 23% and of relapse 11%. The incidence of acute GvHD grade II-IV was 22% in HLA matched and 50% in HLA mismatched pts (p=0.022), grade III-IV was 6% and 25% respectively (p=0.042) . The incidence of moderate-severe chronic GvHD was 25% in HLA matched and 36% in HLA mismatched grafts (p=0.36). HLA had a major impact on survival : 85% vs 49% survival for matched vs mismatched patients (p=0.01). Patients age &gt;60 years had a major impact on outcome, with a 2 year survival of 51% vs 88% in patients over (n=24) or under 60 years of age (n=32) (p=0.007; the DFS was 46 % and 80% respectively and the CI of TRM was 42% vs 9% (p=0.003). As to the total dose of busulfan, we found 26% TRM in patients receiving busulfan for 2 days (total doe 6.4 mg/kg) (n=47) and 0% in older patients receiving 1 day only (total dose 3.2 mg/kg) (n=8) ; relapse rate was 10% and 20% respectively. In multivariate cox analysis including age, spleen size ,DIPSS score, number of transfusion received and donor type, only HLA matching influenced the incidence of acute GvHD; transfusion burden and age plays a role in NRM and OS; DIPSS predicts relapse . In conclusion: older patients with MF have a high NRM and need to be prepared with a milder conditioning regimen. Disclosures Laurenti: Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

scholarly journals AL Amyloidosis: The Effect of Maintenance Therapy on Autologous Stem Cell Transplantation Outcomes

2020 ◽  
Vol 9 (11) ◽  
pp. 3778
Author(s):  
Michael Ozga ◽  
Qiuhong Zhao ◽  
Don Benson ◽  
Patrick Elder ◽  
Nita Williams ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Prognostic Significance ◽  
Al Amyloidosis ◽  
Effective Treatment Option ◽  
Significant Difference ◽  
The Impact

Background: Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic light chain (AL) amyloidosis. While maintenance post ASCT in multiple myeloma is now standard, the decision to utilize maintenance in AL amyloidosis remains largely unexplored. The present study aims to determine the prognostic significance of utilizing maintenance therapy following ASCT and assess the impact of fluorescent in situ hybridization (FISH) abnormalities, bone marrow plasma cell burden (BMPC), and degree of organ involvement on this decision. Methods and results: This is a retrospective analysis of fifty AL amyloidosis patients who underwent ASCT at The Ohio State University. Twenty-eight patients received maintenance and twenty-two did not. Kaplan–Meier survival analysis was used to compare the effect of maintenance therapy with no significant difference in PFS (p = 0.66) and OS (p = 0.32) between the two groups. There was no difference in survival based on maintenance when further categorized by FISH, PFS (p = 0.15), and OS (p = 0.65); BMPC ≥ 10%, PFS (p = 0.49), and OS (p = 0.32); or with 2 or more organs involved, PFS (p = 0.34) and OS (p = 0.80). Conclusion: Maintenance therapy post ASCT did not impact PFS or OS when categorized by FISH abnormalities, increasing BMPC, or ≥2 organs involved in AL amyloidosis patients.

Incompatibilities of HA-1 and CD62L Polymorphic Adhesion Molecule Induce Graft-versus-Leukemia Effect Rather Than GVHD Resulted in Long-Term Survival in HLA Identical Myeloablative Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1639-1639
Author(s):  
Takamasa Katagiri ◽  
Shintaro Shiobara ◽  
Tatsuo Furukawa ◽  
Jyunichi Tsukada ◽  
Shinji Nakao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Survival Rate ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Acute Gvhd ◽  
Term Survival ◽  
Standard Risk ◽  
Better Than

Abstract Mismatches of minor histocompatibility antigen ( mHag) between HLA identical stem cell donor and host are known as a major risk factor for graft-versus-host disease (GVHD). We determined alleles of 5 polymorphic molecules including HA-1 and 4 adhesion molecules for 107 patients stem cell transplanted from HLA identical donors and investigated the association of their mismatches with relapse rate and GVHD. All of 107 recipients received stem cell transplantation ( SCT) after myeloablative conditioning regimen from 1978 to 2002, 89 received marrow, 15 received PBSC and 3 received both. Stage of the disease at SCT was 63 in standard risk and 43 in high risk. After SCT, 37 developed acute GVHD( ≥2), 50 developed chronic GVHD and 31 relapsed during at least 2 years follow up period. We observed 16.1% of relapse rate in patients with at least one or more incompatibilities and 39.3% of relapse rate without incompatibilities (P= 0.018). Relapse rate of patients with CD62L, HA-1, CD31 at codon 563, CD31 at codon 125 and 49b incompatibilities are as followed 6.1%, 14.3%, 11.7%, 20% and 40% respectively. No difference of acute GVHD was observed in patients with and without incompatibilities. Among standard risk patients, 11 patients with HA-1 incompatibility showed 0% of relapse rate which was better than 45% (P= 0.003) in 47 patients without HA-1 incompatibility. In addition, 10 year survival rate was 100% in the former patients which was better than 52% of survival rate (p=0.03) in the latter patients. These data suggests that polymorphic molecules of HA-1 and CD62L contribute to GVL effect rather than the developing of GVHD which resulted in long term survivor after HLA identical stem cell transplantation. Mhag analysis of donor and host in addition to HLA antigen will help a patient to find a suitable donor in HLA identical family and voluntary donor. Figure Figure

Prevention of Acute GVHD with Sirolimus Does Not Abrogate the Risk of Chronic GVHD.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3317-3317
Author(s):  
Corey Cutler ◽  
Shuli Li ◽  
Haesook T. Kim ◽  
Edwin Alyea ◽  
Vincent Ho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Serum Level ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Tissue Injury ◽  
Chronic Gvhd ◽  
Effective Prevention ◽  
Gvhd Prophylaxis

Abstract Chronic graft-vs.-host-disease (cGVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation. The pathophysiology of cGVHD is poorly understood, but allogeneic T and B cells are thought to be important mediators of tissue injury. Risk factors for cGVHD include mismatched or unrelated transplantation, the use of peripheral blood stem cells, increased age and sex mismatching. Prior acute GVHD (aGVHD) is the most important risk factor and therefore strategies that reduce aGVHD are expected to reduce cGVHD as well. We have described a novel GVHD prophylaxis regimen comprised of sirolimus and tacrolimus that is effective in reducing aGVHD. Here, we report cGVHD outcomes with this novel regimen. Methods: 53 patients underwent HLA-matched sibling peripheral blood stem cell transplantation using cyclophosphamide and TBI conditioning. The GVHD prophylaxis regimen was comprised of sirolimus (target serum level 3–12 ng/ml) and tacrolimus (target serum level 5–10 ng/ml) without methotrexate. Median follow-up is 11 months from transplantation. Results: The incidence of grade II-IV aGVHD was 19%. Of the 10 patients with aGVHD, only 3 developed cGVHD. In these three patients, aGVHD had resolved entirely. In total, 21 patients developed cGVHD at a median of 231 days from transplantation, 18 of whom had no prior aGVHD. The cumulative incidence of cGVHD was 63% when relapse and death were considered as competing risks. At the time of cGVHD diagnosis, 10 patients were off all immunosuppressive medications, 6 patients were on sirolimus, either alone(2) or in combination with tacrolimus(4). 3 patients were on tacrolimus, either alone (2) or with prednisone(1), 1 patient was on prednisone alone and information was unavailable for 1 patient. cGVHD end-organ involvement included liver(13), skin(12), oral mucosa(12), eye(6), musculoskeletal(5), hematologic(1), lung(1) and serosa(1). 3 patients had isolated, limited hepatic cGVHD. Therapy included the re-institution of prednisone alone(5) or with mycophenolate(6), sirolimus(4), tacrolimus(2), rituximab(1) or multiple agents(1). One patient began on mycophenolate alone and 1 patient required no therapy. 4 patients had a complete response to immunosuppressive therapy. Only 1 patient died after the diagnosis of cGVHD while still on immunosuppression. No patient with cGVHD had malignant disease relapse. Conclusions: Despite effective prevention of aGVHD with sirolimus and tacrolimus, cGVHD was not prevented in this patient cohort. This argues that the pathophysiologic mechanisms involved in tissue injury in aGVHD and cGVHD may be different, or that methotrexate may be important in the prevention of cGVHD. Since the development of antibodies directed against minor histocompatibility antigens has been correlated with the development of cGVHD, novel strategies designed to interfere with B cell immunity after transplantation may be required to prevent cGVHD.

A Possible Association between the Presence of Interleukin-4-Secreting Cells and a Reduction in the Risk of Acute Graft-Versus-Host Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4968-4968
Author(s):  
Maki Takabayashi ◽  
Heiwa Kanamori ◽  
Hirotaka Takasaki ◽  
Satoshi Yamaji ◽  
Hideyuki Koharazawa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Interleukin 4 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract We monitored interleukin-4 (IL-4), interferon-gamma (IFN-g), and tumor necrosis factor alpha (TNF-a)-secreting cells using an enzyme-linked immunospot (ELISPOT) assay in a prospective study to assess the cytokine network after transplantation. Peripheral blood mononuclear cells were collected from 23 patients who received allogeneic stem cell transplantation, from before the preconditioning regimen to 56 days after transplantation. The frequency of IL-4-secreting cells was significantly higher in 5 patients receiving peripheral blood stem cell transplantation (PBSCT) than that in 18 patients who received bone marrow transplantation (BMT). Based on IFN-g and TNF-a release, there was a trend toward a decrease in the number of cytokine-secreting cells in PBSCT. Furthermore, patients who did not develop acute graft-versus-host disease (GVHD, n = 5) showed a significantly higher number of IL-4-secreting cells compared with those who developed acute GVHD (n = 18). These results indicate that the high percentage of IL-4-secreting cells may be responsible for the inhibition of acute GVHD. In addition, the increased percentage of IL-4-secreting cells may be responsible for the unexpected low incidence of acute GVHD in PBSCT, despite the presence of large numbers of mature T cells in the donor infusion.

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