Nonmyeloablative Stem Cell Transplantation Research Articles

Improved T-Cell Chimerism and Successful Withdrawal of Immunosuppression after Non-Myeloablative Stem Cell Transplantation for Sickle Cell Disease with Azathioprine/Hydroxyurea Preconditioning Added to Alemtuzumab/TBI Conditioning

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only established curative treatment option for sickle cell disease (SCD). In adult SCD patients, myeloablative conditioning is associated with significant toxicity, primarily because of cumulative organ damage. Recently, matched sibling donor (MSD) transplantation with non-myeloablative conditioning (alemtuzumab/3 Gy total body irradiation (TBI)) showed promising outcomes in adult SCD patients. This chemotherapy-free regimen, typically resulting in mixed chimerism, is associated with mild toxicity with no reports of graft-versus-host disease (GvHD). Despite mixed chimerism, the red blood cell (RBC) phenotype is completely donor-derived. However, in a large series, 13% of patients experienced graft failure. Another 8.2% of patients could not stop their immunosuppression (sirolimus) after one year, because of low donor T-cell chimerism (<50%). Reported mean donor T-cell chimerism at 12-months post-transplantation was 48% (Br J Haematol. 2021 Feb;192(4): 761-768). We hypothesized, that the addition of azathioprine and hydroxyurea as preconditioning to the alemtuzumab/TBI conditioning regimen will reduce the risk of graft failure and improve donor T-cell chimerism, enabling successful withdrawal of sirolimus in all patients. Aim: To investigate the effects of adding azathioprine/hydroxyurea preconditioning to alemtuzumab/TBI conditioning on donor chimerism levels and the occurrence of graft failure in adult SCD patients receiving non-myeloablative MSD-HSCT. Methods: Adult SCD patients with an available HLA-identical sibling donor were eligible for this treatment. All patients received three months of azathioprine 150mg qd and hydroxyurea 25mg/kg qd preconditioning. After exchange transfusion (target HbS <30%), conditioning with alemtuzumab 1mg/kg total dose and 3Gy TBI started on day -7, followed by unmanipulated peripheral hematopoietic stem cell infusion on day 0. Sirolimus as GvHD and rejection prophylaxis started on day -1. Results: Twenty SCD patients (median age 26 (range 19-49) years) were transplanted with a median follow-up of 24.5 months (range 1-52 months). Patient and transplant characteristics are shown in Table 1. Median donor myeloid and T-cell chimerism of engrafted patients was 100% (range 87-100%) and 68.5% (range 37-89%) at 12-months post-transplantation and 94% (range 86-100%) and 78.5% (range 68-88%) at 18-months post-transplantation, respectively (Figure 1). These donor T-cell chimerism percentages are higher than previously reported with alemtuzumab/TBI conditioning only. All engrafted patients had a corrected SCD phenotype with normalized hemoglobin levels. Importantly, all patients with a follow-up of ≥ 12 months (n=12) could successfully taper and stop sirolimus without decreases in donor chimerism. One year estimated disease-free survival and overall survival were 94.7%. and 93.3%, respectively. One patient (5%) experienced graft failure without autologous regeneration and subsequently died after a series of complications, including EBV reactivation, post-transplantation lymphoproliferative disease, and systemic aspergillosis. Acute gastrointestinal GvHD grade 2 occurred in one patient (5%) and resolved quickly after treatment with prednisolone. Summary/Conclusion: Azathioprine/hydroxyurea preconditioning prior to alemtuzumab/TBI resulted in improved donor T-cell chimerism, potentially reducing the risk of graft failure after non-myeloablatieve MSD transplantation in SCD patients. Importantly, all engrafted patients reached donor T-cell chimerism >50% and were able to stop immunosuppressives as scheduled. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcomes of non-myeloablative allogeneic stem cell transplant in older patients with acute myeloid leukaemia in first remission.

The benefits of non-myeloablative stem cell transplant in older patients with acute myeloid leukaemia are unclear. We compare the long-term outcomes of this regimen in those aged 55-65 years in first remission with a chemotherapy only cohort that achieved durable morphologic remission. Five-year overall survival was similar (32% vs 33%, P = 0.90), as was relapse-free survival (23% vs 20%, P = 0.37). There was a trend for decreased relapse that was balanced against increased non-relapse mortality with transplantation.

Long--Term Free Survival of Two Class III β-Thalassemic Patients after Non-Myeloablative Stem Cell Transplantation

At present, hematopoietic stem cell transplantation is the only curative treatment for β thalassemia patients. Conventional myeloablative stem cell transplantation is associated with significant morbidity and mortality, and non-myeloablative stem cell transplantation is associated with high graft failure rate. Some modification in this treatment approach can result in successful transplantation in thalassemia patients. Two successful Fludarabine-based non-myeloablative stem cell transplantation in two Class III β thalassemia patients are reported here. The first patient was a 14-year old girl that developed rapid engraftment and full chimerism after rapid tapering of cyclosporine as graft-versus-host disease (GVHD) prophylaxis drug according to our protocol. Another patient was a 24-year old female patient that developed cyclosporine toxicity, and early tapering of cyclosporine helped for rapid engraftment and successful transplantation. After these two successful experiments in non-myeloablative peripheral blood stem cell transplantation for our class III β thalassemia patients, we concluded that Fludarabine-based non-myeloablative stem cell transplantation with adequate number of stem cells at the time of transplantation and rapid tapering of GVHD prophylaxis drugs after transplantation can potentially help for rapid engraftment and successful stem cell transplantation in high risk β-thalassemia patients.

Risk factors associated with the development of moderate to severe chronic graft-versus-host disease after non-myeloablative conditioning allogeneic stem cell transplantation in patients with AML or MDS

Moderate to severe chronic graft-versus-host disease (cGVHD) is associated with high morbidity, hospital dependency and poor quality of life. In this study, we analyzed a well-defined consecutive series of 98 patients with acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) who received allogeneic stem cell transplantation with non-myeloablative (NMA) conditioning to determine risk factors associated with the severity of cGVHD. cGVHD was defined according to the 2005 National Institute of Health consensus criteria. Transfusions before transplantation, presence of HLA antibodies, composition of the graft (CD3+, CD19+, CD34+ cells), sibling or matched unrelated donor, female donor to male recipient, CMV serology and the development of acute GVHD (aGVHD), were considered potential risk factors. Multivariate Cox regression analysis identified the number of CD19+ 106/kg (HR 2.79; 95% CI 1.35–5.74), CD3+ 106/kg (HR 2.18; 95% CI 1.04–4.59) infused cells and the presence of patient HLA antibodies before transplantation (HR 2.34; CI 1.11–4.95) as significant risk factors for the development of moderate to severe cGVHD. In summary, we identified in a small, but well-defined cohort, 3 risk factors associated with the severity of cGVHD that should be validated in a larger multi-center study.

Characterization of Immune Cells Producing Regulatory Cytokines That Mediate Engraftment in Sickle Cell Disease Patients after Haploidentical Peripheral Blood Stem Cell Transplantation

Sickle cell disease (SCD) is an inherited blood disorder in which red blood cells are sickle-shaped as a result of an amino acid alteration from glutamate to valine at the sixth position of the β-globin chain. Hematopoietic stem cell transplant (HSCT) is a curative option for SCD, with both HLA-matched and haploidentical transplant being viable approaches. Stable mixed chimerism and tolerance induction are sufficient to reverse the sickle phenotype. Graft rejection and graft versus host disease may occur following nonmyeloablative haploidentical peripheral blood stem cell transplantation (PBSCT). Various regulatory cytokines have been identified as biomarkers of engraftment in graft transplantation. Previously, we observed that TGF-β, interleukin (IL)-7, and IL-10 cytokines were elevated in engrafted SCD patients as compared to those who rejected their grafts following haploidentical PBSCT. Now, we aim to identify the immune cell populations responsible for producing the above cytokines in both engrafted and rejected patients. The plasma samples of 21 SCD patients who underwent nonmyeloablative haploidentical PBSCT at the National Institutes of Health between March 2010 and September 2015 were evaluated previously by multiplexed magnetic bead enzyme linked immune sorbent assay. Here, we analyzed various immune cells which produce the above regulatory cytokines through multi-color flow cytometry in 8 out of the 21 patients (four engrafted and four rejected). We evaluated the cytokine producing capabilities via intracellular cytokine detection among T regulatory (Treg, CD3+CD4+CD25+Foxp3+) cells, Type 1 regulatory (Tr1, CD3+CD4+Foxp3-CD45RA-CD49+LAG3+) T cells, T helper 1 (Th1, CD3+CD4+Foxp3-CD45RO+CXCR3+) cells, T helper 17 (Th17, CD3+CD4+Foxp3-CD45RO+CCR6+) cells, natural killer (NK, CD3-CD56+NKG2D+) cells, B regulatory (Breg, CD3-CD56-CD19+CD24hiCD38hi)cells, polymorphonuclear-myeloid derived suppressor cells (PMN-MDSCs, CD45+CD14-CD15+CD11b+), monocytic-MDSCs (CD45+CD14+CD15-HLADRlow), early-MDSCs (CD45+Lin-HLADR-CD11b+CD33+), myeloid dendritic cells (mDCs, CD45+CD3-CD56-HLADR+CD11c+CD123-), and plasmacytoid dendritic cells (pDCs, CD45+CD3-CD56-HLADR+CD11c-CD123+). Cytokine producing cell frequencies were measured at five timepoints: baseline (day 0) and days 30, 60, 100, and 180 post-transplant (PT). Percentages of intracellular cytokine and cell population frequencies were assessed through flow cytometry analysis and statistical significance was determined by Student's t-test. We noted IL-10-producing Tregs were significantly elevated in engrafted patients at PT day 100 (p&amp;lt; 0.01, see Figure 1). Further, IL-10-producing Th1 cells were significantly higher in engrafted patients on PT day 30 (p&amp;lt; 0.01) and day 100 (p&amp;lt; 0.01). However, rejected patients had significantly higher amounts of IL-10-producing PMN-MDSCs (p&amp;lt; 0.01), and myeloid DCs (p&amp;lt; 0.01, see Figure 2), but their levels were lower than IL10-producing Tregs and Th1 cells of engrafted patients. There were no significantly different alterations of IL-10-producing cell frequencies among other cell populations (Tr1, Th17, NK, Breg, early-MDSCs, monocytic-MDSCs, and pDCs). In addition, there were no significant variations in TGF-β- and IL-7-producing cell frequencies in any of the immune cell populations tested. Overall, the engrafted patients showed higher IL-10-producing Tregs and Th1 cells at PT day 30 and/or day 100, which suggest that the immunosuppressive cytokine IL-10 may play an important role in engraftment. Further analyses with a larger sample size are indicated to evaluate whether IL-10 producing immune regulatory cells may serve as a biomarker to predict transplant outcome. Taken together, continuous regulatory cytokine analysis at serial time points pre- and post-transplant may aid in establishing mechanisms of successful engraftment and tolerance induction. Disclosures No relevant conflicts of interest to declare.

Hematopoietic Stem Cell Transplantation and Disease Progression in Relapsing-Remitting MS

To compare nonmyeloablative hematopoietic stem cell transplantation (HSCT) to standard multiple sclerosis (MS) disease-modifying therapies (DMTs),

Patients´ experiences and perspectives of challenges and needs related to nonmyeloablative stem cell transplantation: Involving patients in developing a targeted rehabilitation programme.

To explore patients' experiences and perspectives of their challenges and needs regarding their return to everyday life after allogeneic nonmyeloablative haematopoietic stem cell transplantation (NMA-HSCT). NMA-HSCT can cure patients with malignant blood diseases, but during the following years, the majority of patients suffer from serious side effects and complications. Hence, it is a major challenge for patients treated with NMA-HSCT to rehabilitate, maintain physical and psychosocial functioning and return to a life in restored balance. The design was qualitative using the interpretive description methodology, and the theoretical framework symbolic interactionism inspired the interview guide and analysis. Between April to May 2017, five focus group interviews were conducted with 15 outpatients in a haematological ward in Denmark. The patients were treated with NMA-HSCT 8-30months prior to the interviews. The study adheres to the Consolidated Criteria for Reporting Qualitative Research guidelines. The impaired functioning was the overarching theme and seemed to be the trigger entailing rehabilitation needs related to the following main themes: realising decline, adapting to changes, the meaning of motivation and reliance on relations. These findings seemed to affect and influence the patients' struggle for a return to an everyday life like before being diagnosed or just before undergoing NMA-HSCT. This study adds to our understanding of important elements to consider when developing a targeted rehabilitation programme. Based on our findings, the rehabilitation programme should encompass: extensive variation regarding how to address the impaired functioning through individualised approaches, multimodal interventions, interventions through several months with varying intensity, an interdisciplinary team approach supporting motivation and visualisation of every progress by tangible goal setting, communication regarding hope and support, extended supportive care for patients living alone and finally increased adherence through social sessions with relatives and fellow patients.

Fludarabine/cyclophosphamide (Flu/Cy) non-myeloablative allogeneic stem cell transplant for aplastic anemia and hypoplastic myelodysplasia: A single institution experience.

e19021Background: Allogeneic hematopoietic stem cell transplant (HSCT) is a potentially curative option for severe aplastic anemia (SAA) or hypoplastic myelodysplasia (h-MDS). However, there is no ...

OR10 Analysis of engraftment kinetics of donor-type chimerism in lineage-specific cell populations after allogeneic hematopoietic stem cell transplantation

Aim The aim was to monitor the engraftment patterns and outcome of the graft by quantitative lineage chimerism testing based on short tandem repeats (STR), focusing on a longitudinal analysis post allogeneic myeloablative (MA) and nonmyeloablative (NMA) hematopoietic stem cell transplantation (HSCT). Methods The study was conducted on a cohort of 45 patients who received an allogeneic HSCT. All grafts were from a HLA ‘full house’ matched related donor. Post-transplant peripheral blood samples were collected from the recipient at D + 21, D + 30, D + 60, D + 90, D + 120, D + 180 and D + 365. Whole blood mononuclear cells was fractionated into CD3+, CD15 + and CD56 + cells using magnetic beads with sequential positive selection before extracting DNA. Sixteen STR (microsatellite) loci (D8S1179, D21S11, D7S820, CSS1PO, D3S1358, THOI, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, Amelogenin, FGA and D5S818) were amplified by multiplex PCR and the amplicon resolved on DNA sequencer. Results Post-transplant at D + 21 the percentage of donor T-cell chimerism was 100% in 17.9% cases whereas, the myeloid and NK cell donor chimerism was found to be 65% and 47.3% respectively. Overall the NK cell chimerism pattern closely approximated myeloid cell chimerism, while T cell recovery was distinctly different. In the MA category the donor chimerism reached >90% earlier than the NMA group. At D + 21 in the MA cohort, the average percentage of donor cells in CD3+, CD56+, CD15 + lineages was 84.12%, 93.92% and 97.61% whereas in the NMA cohort it was 79.4%, 85.7% and 90.99% respectively. The donor chimerism in MA group at D + 90 was >97% in all lineages, whereas in NMA group the donor cells in the three lineages were CD3 90.5%, CD56 92.8% and CD15 98.9%. The percentage of CD15 cells was higher at all-time points as compared to CD56 and CD3. In relapse the T cell chimerism showed maximum variation while myeloid cells demonstrated a more stable graph. No definite chimerism pattern was detected in the three lineages in ac GVHD. Conclusions This study establishes that, longitudinal chimerism testing is an important parameter for surveillance of engraftment and provides important information on disease recurrence or graft loss in HSCT. As a monitoring approach, it exploits the ability of the STR technique to compare numerical results between samples.

Role of non-myeloablative allogeneic stem cell transplant in chronic lymphocytic leukemia and its implications in current era: A systematic review.

e18536Background: TP53 mutated or del(17p) chronic lymphocytic leukemia (CLL) has high incidence of transformation to high-grade lymphoma. Ibrutinib is approved as first line agent for these high r...

Long-term outcomes of non-myeloablative allogeneic stem cell transplantation (alloSCT) in patients with relapsed mantle cell lymphoma (MCL).

7551Background: Patients with relapsed MCL remain incurable, especially if their tumors have a Ki-67 > 30%. We analyzed the long-term survival outcomes of 75 recipients of alloSCT. Methods: Patient...

HLA-Mismatched Microtransplantation Vs HLA-Matched Nonmyeloablative Transplantation for Acute Myeloid Leukemia in Intermediate-Risk: Comparable Survival but Avoids of Gvhd

The optimal therapy for intermediate-risk patients with acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Recent studies shown that microtransplantation (MST) can improve survival in AML-CR1 patients. However, a comparison study between the MST and nonmyeloablative stem cell transplantation (NST) is lacking. 156 intermediate-risk AML-CR1 patients aged 9 to 59 years were enrolled in this study. 57 patients who had a HLA-identical donors were assigned to receive NST therapy with graft-versus-host disease (GVHD) prophylaxis. The other 99 who had no HLA-identical donors including 86 family-related, 9 distantly related and 4 unrelated donor were assigned to receive MST therapy but without GVHD prophylaxis. The probabilities of 10-year overall survival and leukemia-free survival was comparable in the MST-group and NST-group (70.7% vs. 61.4% and 59.6% vs. 57.9%). The NST-group exhibited a higher full donor chimerism (96.5%) and higher GVHD (33.3%), whereas the MST-group produced a higher donor microchimerism (75%), slightly higher relapse (32.3% vs. 22.8%) and significantly lower non-relapse mortality (6.9% vs. 19.3%, P=0.021) but without GVHD. In the MST-group, the patients with increase of WT1+ CD8+ T cells exhibited significantly higher leukemia-free survival and lower relapse than those without (92.0% vs. 40.0%, P=0.003; 8.0% vs. 50%, P=0.009). These results indicate that, compared to NST, MST produced a comparable survival, less transplantation-related mortality, avoidance of clinical GVHD and overcome limitations of HLA-barrier, suggesting a much safe and effective therapy for intermediate-risk AML-CR1, particularly for those without a HLA-identical donor. DisclosuresNo relevant conflicts of interest to declare.

Outcomes of Salvage Stem Cell Transplantation in Hodgkin Lymphoma in a Single Institution in the Modern Era

Background: Though overall Hodgkin lymphoma (HL) carries one of the best outcomes among lymphoma, about 40% of patients relapse and/or fail to respond to initial therapy. Out of those about half can be cured with salvage therapy followed by high dose therapy and autologous stem cell transplantation (ASCT) while eligible patients who fail and/or relapse after HDT-ASCT are offered nonmyeloablative stem cell transplantation. Achieving a negative PET response prior to ASCT correlate with superior outcome in HL regardless of their clinical presentation. More recently novel therapies have emerged in the field from brentuximab vedotin approved in r/r setting in HL as well as checkpoint inhibitors currently in trials with very promising results. This study analyzed a cohort of HL pts transplanted at our institution over the last 5 years to identify potential new patterns in the evolving landscape of HL.Methods: We performed a retrospective analysis of r/r HL pts referred to our center for salvage therapy at our institution between 2009 and 2014 using the Blood and Bone marrow transplant database at HUMC.Results: A total of 66 patients with r/r HL transplanted at HUMC were identified. Baseline characteristics were as follows: male 57%, female 43%, median age 36.8y (range 16-66), Frontline therapy was ABVD in all but one pt who received Gemzar, Vinorelbine, Doxil; and 27% pts received consolidation w/ radiation. Median time to relapse was 7mo (range 0.93-87mo), stage at first relapse I-0, II-33%, III-20%, IV-23%, NA 24%. The salvage regimen used was ICE in 54 pts, brentuximab vedotin in 8 pts and HCVAD in 4 pts. Involved field radiation was used in 10% at salvage prior to HDT-ASCT. Responses after first salvage were as follows: PET-CR 59%, CT-CR 5%, PR-14%, PD-12%, NA-10%. As per our practice, pts not in CR after first salvage continue to the next salvage until they reach a CR. Pts not in CR after 2 lines of salvage were considered for allogeneic stem transplantation (alloSCT). Conditioning regimen was BEAM prior to ASCT, reduced intensity (fludarabine-based) prior to alloSCT. Source of allo stem cells was: MRD in 7 pts, MUD in 3 pts, haploidentical donor in 2 pts. A total of 59 pts had ASCT, 6 pts had alloSCT as first transplant (primary refractory), while 6 pts underwent alloSCT for relapse after ASCT. Disease status post first transplant was as follows: PET-CR 76%, CT-CR 17%, PR-1%, PD-6%. All 6 alloSCT pts are alive in remission, while 13 out of 59 ASCT pts have relapsed, 7 relapses occurred within the first year, 3 within the second year post ASCT. Out of 6pts with alloSCT after ASCT relapse, 4 pts are alive in CR, one died from PD, one died from PTLD (in CR from HL). After a median follow up of 24.5 mo (3.7-70), the 3y PFS and OS are 73% and 95% respectively. For CR and PR after first salvage to SCT pts, median PFS and OS has not been reached. For SD/PD after first salvage therapy pts median PFS is 14.5mo, median OS 47mo. No significant difference in mPFS and mOS is seen in pts who received one vs more than one salvage therapy prior to ASCT or had radiation as part of frontline or salvage therapy.Conclusion: We report on a consecutive series of high-risk r/rHL. Our results demonstrate an improved outcome compared to historical data. Pts requiring more than one salvage prior to SCT while having mPFS of only 14.5 mo, have prolonged survival at median 47 mo.While the number is small, selected young pts with high risk relapsed HL may benefit from alloSCT. Strategy of requiring CR prior to SCT, and alloSCT (instead of ASCT) in pts requiring more than 2 consecutive salvage regimens, availability of novel agents, diminishing use of RT may have contributed to observed improved outcomes. DisclosuresFeldman:Pharmacyclics/JNJ: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau. Vesole:Idera Pharmaceuticals: Research Funding; Celgene Corporation: Speakers Bureau. Skarbnik:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau. Goy:Acerta: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/JNJ: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease

Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely performed in adult patients with sickle cell disease (SCD). We utilized the chemotherapy-free, alemtuzumab/total body irradiation 300 cGy regimen with sirolimus as post-transplantation immunosuppression in 13 high-risk SCD adult patients between November 2011 and June 2014. Patients received matched related donor (MRD) granulocyte colony–stimulating factor–mobilized peripheral blood stem cells, including 2 cases that were ABO incompatible. Quality-of-life (QoL) measurements were performed at different time points after HSCT. All 13 patients initially engrafted. A stable mixed donor/recipient chimerism was maintained in 12 patients (92%), whereas 1 patient not compliant with sirolimus experienced secondary graft failure. With a median follow-up of 22 months (range, 12 to 44 months) there was no mortality, no acute or chronic graft-versus-host disease (GVHD), and no grades 3 or 4 extramedullary toxicities. At 1 year after transplantation, patients with stable donor chimerism have normalized hemoglobin concentrations and improved cardiopulmonary and QoL parameters including bodily pain, general health, and vitality. In 4 patients, sirolimus was stopped without rejection or SCD-related complications. These results underscore the successful use of a chemotherapy-free regimen in MRD HSCT for high-risk adult SCD patients and demonstrates a high cure rate, absence of GVHD or mortality, and improvement in QoL including the applicability of this regimen in ABO mismatched cases (NCT number 01499888).

Dietary created niche for non-myeloablative hematopoietic stem cell transplantation

Dietary created niche for non-myeloablative hematopoietic stem cell transplantation

Impact of outpatient non-myeloablative haematopoietic stem cell transplantation in quality of life vs. conventional therapy

The role of outpatient hematopoietic stem cell transplantation (HSCT) as a therapeutic tool has been strengthened significantly because of the increasing number of patients undergoing this treatment. Due the very nature of this procedure, one of the aspects that should not be overlooked is the quality of life (QOL) of patients undergoing HSCT. Thus, one must consider not only health status after treatment, but also, the psychosocial implications for the patient. This is an observational, longitudinal, and prospective study to assess QOL in patients undergoing outpatient HSCT vs. similar patients receiving medical treatment (MxTx). By applying the COOP/WONKA charts on five occasions (pre-HSCT/initial, post-HSCT/first month, and at 3, 6, and 9 months), thirty-eight patients were analysed, 19 with HSCT and 19 with MxTx with no differences in age, gender or diagnosis. The initial survey found significant differences only in pain perception, which was higher in the HSCT group (p = .08); at the first month, there was a greater tendency for feelings of depression or anxiety in the HSCT group (p = .016), with more limitations in social (p = .003) and daily (p = .044) activities. From 3 months post-HSCT, the results were very similar. The differences persisted only in the area of social activities. Four patients developed graft-versus-host disease with no significant difference in the scores obtained compared to other transplant patients at 3, 6, and 9 months (p = .26) of follow-up.

782 Renal cancer treatment with recipient lymphocyte infusion enhanced the antitumor effect of nonmyeloablative allogeneic stem cell transplantation

782 Renal cancer treatment with recipient lymphocyte infusion enhanced the antitumor effect of nonmyeloablative allogeneic stem cell transplantation

Nonmyeloablative Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Nonmyeloablative hematopoietic stem cell transplantation (HSCT) has been hypothesized to reset the immune system and provide long-term benefit in some

Clinical Comparison of Non-Myeloablative Conditioning with Anti-Thymocyte Globulin and Fludarabine for Patients with Hematologic Malignancies

BackgroundThe influence of different non-myeloablative conditioning regimens on clinical outcome remains undefined.Material/MethodsWe retrospectively analyzed the hematopoietic reconstitution, graft-versus-host disease (GVHD), and quality of life (QOL) in 56 patients with hematologic malignancies who underwent non-myeloablative stem cell transplantation (NST) with a conditioning regimen based on anti-thymocyte globulin (ATG), followed by donor lymphocyte infusion (n=24), or Fludarabine (FLU) (n=32). Hematopoietic stem cells were derived from low-resolution HLA-matched identical sibling donors.ResultsThe blood type transformation and platelet reconstitution presented significantly earlier in the FLU group than the ATG group (P<0.05). Within 100 days post-transplantation, the incidence of grade I–IV acute GVHD was significantly lower in the ATG group than the FLU group (P<0.05). After 100 days post-transplant, extensive chronic GVHD (cGVHD) was more prevalent in the ATG group than the FLU group (P<0.05). There were lower cumulative risk of relapse and higher non-relapse-related mortality in the ATG group, but better QOL in the FLU group within 24 months, and no difference in 3-year disease-free survival (DFS) or overall survival (OS) between the 2 groups (P>0.05).ConclusionsThe FLU-based conditioning regimen improved hematopoietic reconstitution and decreased extensive cGVHD, but there was no difference in 3-year DFS or OS between the 2 groups.

Renal cancer treatment with recipient lymphocyte infusion enhanced the antitumor effect of nonmyeloablative allogeneic stem cell transplantation

BackgroundNonmyeloablative allogeneic stem cell transplantation (SCT) is an option for the treatment of metastatic renal cancer. Mature donor T cells cause graft versus-host disease (GVHD) although they are also the main mediators of the beneficial graft-versus-tumor (GVT) activity associated with this treatment. Hence, the segregation of GVT activity from GVHD is an important challenge in managing the clinical course of treatment. We previously reported a series of studies regarding the allograft tolerance induced by allogeneic spleen cells (with bone marrow cells) and cyclophosphamide in mice. MethodsThe aim of the present study was to modify the cyclophosphamide-using cell therapy to reduce the risk of GVHD while preserving the antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma with recipient lymphocyte infusion (RLI). ResultsRegarding the in vivo antitumor effect, there was a significant difference between RLI and no lymphocyte infusion after the cyclophosphamide treatment, whereas the histologic findings of the small intestine showed that the cyclophosphamide-using cell therapy with RLI decreased the risk of GVHD as compared with donor lymphocyte infusion. In addition, the acquired immunity against RENCA was clearly observed in RLI-treated mice. ConclusionsOur results show that RLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate GVT effects from GVHD by reducing the risk of GVHD. We considered that this was the first report to provide the evidence of nonmyeloablative allogeneic SCT with RLI for the treatment of renal cell carcinoma which never induce complete chimerism.