Effect of T-Cell Dose On Outcomes After Peripheral Blood Allogeneic Hematopoietic Cell Transplantation in Hematological Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1171-1171
Author(s):  
Abraham S Kanate ◽  
Farhad Khimani ◽  
Aaron Cumpston ◽  
Kathy Watkins ◽  
Sonia Leadmon ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Hematopoietic Cell ◽  
Cell Dose ◽  
All Cause Mortality ◽  
Cd8 Cell ◽  
One Year

Abstract Abstract 1171 Poster Board I-193 Purpose: Peripheral blood allogeneic hematopoietic cell transplant (HCT) is used to treat various types of hematological malignancies. Current knowledge supports that increased CD34 + cell dose in the infusate is associated with earlier leukocyte recovery. The dose of CD3 +, CD4 + and CD8 + cells is largely disregarded except in T-cell depleted transplant. The correlation between various cell doses and outcomes is an area of great interest in HCT. Our analysis focuses on the impact of T-cell subset dosing, on outcomes after HCT, such as acute graft versus host disease (GVHD) and mortality. Methods: Retrospective analysis was conducted on 134 consecutive patients who underwent peripheral blood allogeneic HCT for various hematological malignancies in our institution between January 2003 and December 2008. Statistical analysis was performed using SPSS 15.0. The Chi - square test was used to determine any association between cell doses and the incidence of acute GVHD and all-cause mortality at one year of follow-up after transplant. Results were also compared with the association between CD3+ and CD8+ cell doses and incidence of acute GVHD as reported in 2007 by our institution. Results: A total of 134 patients were included in our analysis, consisting of 49 females and 85 males. The median age was 49 years (range 17-69). HCT was from matched related donors in 68 and from matched unrelated donors in 66 patients. A variety of conditioning regimens were used in preparation for the HCT. Overall survival at 1 year of follow-up was 60%, the incidence of acute GVHD was 52%, and chronic GVHD was 29%. All-cause mortality at one year follow up was found to be significantly higher when the CD3+ cell dose was < 30.5 × 107/kg IBW (49% vs. 29%, P = 0.018). All-cause mortality was also significantly increased when CD8+ cell dose was < 9.2 × 107/kg IBW (50% vs. 33%, P= 0.05). A CD8+ cell dose of < 9.2 × 107/kg IBW was also associated with an increased risk of grades 2-4 acute GVHD (48% vs. 22%, P = 0.026). There was no association of statistical significance between CD3+ and CD4+ cell doses and the incidence of acute GVHD. Conclusion: The data suggests a statistically significant inverse association between mortality and CD3+ cell dose of <30.5 × 107/kg IBW. A CD8+ cell dose of <9.2 × 107/kg IBW was also associated with increased all-cause mortality and acute GVHD (grades 2-4). Our institution reported in 2007, a significant association between the incidence of acute GVHD (grades 2-4) and CD3+ cell dose < 33.5 × 107/kg IBW and CD8+ cell dose of < 6.2 × 107/kg IBW, based on series of 66 patients. As we increased the sample size to 134, the association between CD3+ cell dose and acute GVHD was no more present. We conclude that T-cell dose is an important factor in terms of outcomes after all allogeneic HCT irrespective of preparative regimen. T-cell subsets likely play a pivotal role in transplant results, though it is not well described. Analysis of larger databases is required to substantiate our results. Disclosures: No relevant conflicts of interest to declare.

Haploidentical Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation (HCT) Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) Conditioning Protects Against Acute Graft Versus Host Disease (GVHD).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2904-2904 ◽  
Author(s):  
R. Lowsky ◽  
K. Heydari ◽  
B. Sahaf ◽  
J. Shizuru ◽  
G. Laport ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Acute Gvhd ◽  
Absolute Number ◽  
Hematopoietic Cell ◽  
T Cell Subsets ◽  
Cell Dose ◽  
Cell Engraftment ◽  
Nk T Cells ◽  
Anti Tumor Activity

Abstract Murine models of transplantation established that nonmyeloablative conditioning using repeated low doses of irradiation targeted to lymphoid tissues (TLI) and depletive anti-T cell antibodies protects against GVHD by skewing residual host T cell subsets to favor regulatory natural killer (NK) T cells that suppress GVHD by polarizing donor T cells toward secretion of non-inflammatory cytokines such as IL-4. We recently translated the murine protocol to a clinical study using non-myeloablative TLI and ATG host conditioning with HLA matched related and unrelated donors, and showed a marked reduction in the incidence of acute GVHD while retaining graft anti-tumor activity (Lowsky et al., in Press NEJM). Engrafted donor CD4+ T cells showed a marked increase in IL-4 production as compared to CD4+ T cells from controls. We now adapted the TLI and ATG nonmyeloablative host conditioning regimen to a clinical study of allogeneic HCT using haploidentical matched (3/6 HLA matched) related donors to determine if it will result in donor hematopoietic cell engraftment and also protect against acute GVHD. Blood derived hematopoietic progenitor cells were collected by apheresis from donors mobilized with G-CSF and the product was T cell depleted using CD34+ selection. CD3+ T cells were added back to the donor inoculum according to a dose escalation schedule. The initial T cell dose was 1 x105 CD3+ cell/kg with designated increments based on clinical outcomes of up to a maximum of 1 x107 CD3+ cells/kg. The desired CD34+ cell dose was >5 x 106 CD34+ cells/kg for all patients. Seven patients were transplanted; the median age was 53 years (range 27 to 61 years). Five patients had acute myelogenous leukemia, two with disease in remission and three not in remission at the start of TLI and ATG, one with myelodysplastic syndrome, and one with progressive peripheral T cell lymphoma. The median follow-up for all patients is 265 days with three of seven patients alive and free of disease at the last observation period. Sustained donor hematopoietic cell engraftment was achieved in three of three patients only after the T cell dose was increased to 1 x107 CD3+ cells/kg. No patient developed acute GVHD. None of the three patients receiving the highest dose of T cells had any invasive fungal or viral infections. Monitoring of sorted host T cell subsets before TLI and ATG, and immediately after but before the infusion of donor cells, revealed in five of five patients a highly significant skewing of residual host T cells favoring invariant NK T (CD3+ CD161hi Va24 +Vb11 +) cells. The mean absolute number of host CD3+, and CD4+ and CD8+ T cells decreased by 99, 163 and 121 fold, respectively, immediately after conditioning compared to the absolute numbers before the start of TLI and ATG, whereas the mean absolute number of invariant NK T cells decreased by only 11%. In conclusion, we have determined the conditions for successful hematopoietic cell engraftment using a non-myeloablative regimen of TLI and ATG that appears associated with a reduced aGVHD risk yet retained graft anti-tumor activity. As in the pre-clinical model, we show direct evidence that the low incidence of aGVHD is associated with a significant alteration in residual host T cell subsets markedly favoring invariant NK T cells.

Balancing Acute Graft Versus Host Disease (aGVHD) and Survival after Peripheral Allogeneic Stem Cell Transplantation (SCT) in Hematological Malignancies: A Potential for Graft Engineering.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3285-3285
Author(s):  
Ayman Saad ◽  
Mohammed Almubarak ◽  
Abraham Kanate ◽  
Aaron Cumpston ◽  
Kathy Watkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Stem Cell ◽  
Survival Analysis ◽  
Acute Gvhd ◽  
Hematological Malignancy ◽  
P Value ◽  
Cell Dose ◽  
Cd8 Cell

Abstract Purpose: Peripheral allogeneic SCT is used to treat different types of hematologic malignancies. The target CD34 stem cell dose is 2 -5 x 106/Kg. The dose of CD3+ cells in the infusate is not taken into account except in T-depleted transplant. T-cell dose in peripheral blood stem cell collections is at least 10-fold more than that in a bone marrow harvest. Regulatory T cells (CD4+, CD25+), which comprises 5–10% of CD4 + T cells have been correlated with less incidence of aGVHD. In our study we are trying to determine the impact of T-cell dosing on the overall survival and incidence of aGVHD after peripheral allogeneic SCT in a group of patients with hematological malignancy. Methods: A retrospective study of 66 consecutive patients who underwent peripheral allogeneic SCT for hematological malignancy in our institution between January 2003 and April 2006. The median duration of follow up after SCT was 12.6 months (range 0.2–53). Duration of follow up was compromised only in a subset of patients who had early mortality following SCT. Proportional hazard model was used to define the cutoff value of CD3, CD4, and CD8 cell dose that separate 2 groups of patients with highest statistically significant difference in terms of incidence of aGVHD. Kaplan-Meier Survival Analysis was used for correlate the overall survival (calculated from date of transplant) among these groups subdivided in terms of CD3, CD4, and CD8 cell doses. Results: The 66 patients (6 females, and 60 males) with median age of 48 years (range: 19–63 years) had different malignancies; 6 ALL, 34 AML, 1 biphenotypic leukemia, 1 CLL, 11 CML, 5 Hodgkin lymphoma, 8 NHL. The SCT was from matched related donors in 39 patients, and from matched unrelated donors in 27 patients. The incidence of aGVHD (grade 2–4) was statistically significantly less among those who received CD3 dose < 33.5 × 107/kg IBW (P value: 0.04), tended to be less among those who received CD4 dose < 32.6 × 107/kg IBW (P value: 0.06), and was statistically significantly less among those who received CD8 dose < 6.2 × 107/kg IBW (P value: 0.04). Survival analysis showed no statistically significantly difference in the overall survival (OS) among all patients groups. Median OS was 10.5 months for those who received CD3 dose ≤ 33.5 ×107/kg IBW and 17 months for those who received > 33.5 ×107/kg IBW (P value: 0.35). Median OS was 12 months for those who received CD4 dose ≤ 32.6 ×107/kg IBW and 16.3 months for those who received > 32.6 ×107/kg IBW (P value: 0.8). Median OS was 6 months for those who received CD8 dose ≤ 6.2 ×107/kg IBW and 14.4 months for those who received > 6.2 ×107/kg IBW (P value: 0.13). Conclusions: In our series, CD3 dose less than 33.5 ×107/kg IBW and CD8 dose less than 6.2 ×107/kg IBW were associated with statistically significant reduced risk of grade 2–4 acute GVHD following peripheral allogeneic SCT. Overall survival was not statistically different among these groups of patients. These data suggest that, in addition to considering CD34 dose required for engraftment in allogeneic transplant, the CD3 dose and its subsets CD8 and CD4 may need to be considered to try to minimize the risk of acute GVHD without compromising survival after transplant.

Higher Infused CD34+ Cell Dose Improves Survival In Patients Undergoing In Vivo T-Cell Depleted, but Not T-Cell Replete Peripheral Blood Hematopoietic Cell Transplant

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1272-1272
Author(s):  
Abraham S Kanate ◽  
Salman Osman ◽  
Aaron Cumpston ◽  
Gerry Hobbs ◽  
Sonia Leadmon ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Univariate Analysis ◽  
Cell Depletion ◽  
Cell Transplant ◽  
Cellular Composition ◽  
T Cell Depletion ◽  
Cell Dose ◽  
Cd8 Cell

Abstract Abstract 1272 Introduction: Allogeneic hematopoietic cell transplant (HCT) remains a potentially curative modality for various hematological disorders. The cellular composition of the infused allograft has important ramifications for transplantation outcomes, for example higher infused CD34+ cell doses have previously been shown to be is associated with early engraftment, improved survival and possibly increased acute graft-versus-host disease (GVHD) following HCT. The influence of cellular composition of infused allograft on transplant outcomes has been the subject of many previous studies. There is paucity of data on the impact of cellular composition of allograft on transplant outcomes of patients undergoing HCT with in vivo T-cell depletion (TCD) compared to patients receiving T-cell replete allografts. We report here a comparative analysis of the impact of CD34+, CD3+, CD4+ and CD8+ cell doses and survival outcomes of allogeneic, peripheral blood HCT patients receiving in vivo T-cell depletion with alemtuzumab or anti thymocyte globulin (TCD group) versus patients who underwent T-cell replete HCT (non-TCD group). Methods: The study cohort includes 150 consecutive patients who underwent allogeneic HCT between January 2003 through December 2009. All patients received peripheral blood allografts from matched sibling or unrelated donors (URD). In vivo T-cell depletion consisted of alemtuzumab 40mg in two divided doses on days -4 and -1 (n=39) or Thymoglobulin at a total dose of 6 mg/kg for ablative and reduced intensity conditioning (RIC) transplants and 7.5 mg/kg total dose for non myeloablative allografts (n=51). 4 patients received Atgam at 30mg/kg on days -5, -4 and -3. Impact of CD34+, CD3+, CD4+ and CD8+ cell doses divided into two groups; >/= 50th and < 50th percentile on overall survival (OS), progression free survival (PFS) and non relapse mortality (NRM) was initially measured by univariate analysis. Multivariate logistic regression analysis was constructed for variables showing significance on univariate analysis (p<0.1). Cellular components of allografts was done by standard flow cytometric techniques. Results: Of the 150 patients, 94 (62.7%) were males. Median age was 49 (range 17–69). Baseline diagnosis included acute leukemia and myelodysplastic syndrome (n=88; 58.6%), chronic myeloid leukemia (n=19; 12.7%), non-Hodgkin lymphoma (n=27; 18%) and others (10.7%). There were 95 patients (63.3%) in the TCD group and 55 (36.7%) in the non-TCD group. The baseline characteristics of the TCD group and non-TCD group were well matched except that significantly more patients in the TCD group had high risk disease (86.3% vs. 61.8%, p = 0.0005) and received allografts from unrelated donors (62.1% vs. 29.1%, p < 0.001). Median doses of the infused cellular components in the allograft were; CD 34+ = 5.8 × 106/Kg (range 1.2 – 16), CD3+ = 30.8 × 107 (4.5 – 100.8), CD4+ = 18.6 × 107 (1.9 – 63) and CD8+ = 11.3 × 107 (0.8 – 52.4). Median follow-up time for surviving patients was 3 years. In the TCD group, multivariate analysis showed that CD34+ cell doses >/= 5.8 × 106 was associated with improved OS (p=0.0085; CI 0.28–0.83), PFS (p=0.03; CI 0.31–0.93) and NRM (p=0.02; CI 0.21–0.89). Multivariate analysis also showed that CD3+ cell dose >/= 30.8×107 improved OS (p=0.03; CI 0.25–0.92), but not PFS (p=0.14; CI 0.16–1.31) and NRM (p=0.15; CI 0.23–1.26). No association was noted between CD4+ and CD8+ cell doses and OS, PFS and NRM (p>0.05), in the TCD group. In the non-TCD group, univariate analysis of CD34+, CD3+, CD4+ and CD8+ cell doses failed to show any statistical significance for NRM, OS and PFS (p>0.1). Conclusion: Our limited, retrospective analysis of 150 peripheral blood allogeneic HCT shows improved OS, PFS and NRM in patients receiving CD34+ cell dose >/= 5.8×106/Kg and improved OS with CD3+ dose >/= 30.8×107/Kg, limited only to the TCD group. No such association was seen in the non-TCD group. We hypothesize that higher CD34+ in TCD transplants probably improved survival by rapid engraftment and by robust immune reconstitution thereby reducing infectious complication otherwise associated with TCD. Disclosures: Abraham: Genentech: Membership on an entity's Board of Directors or advisory committees. Hamadani:Celgene: Honoraria, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau.

Outpatient Haploidentical Peripheral Blood Stem-Cell Transplantation with Post-Transplant Cyclophosphamide in Children and Adolescents

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4389-4389
Author(s):  
Oscar Gonzalez-Llano ◽  
Elias Eugenio Gonzalez-Lopez ◽  
Ana Carolina Ramirez-Cazares ◽  
Edson Rene Marcos-Ramirez ◽  
Guillermo J. Ruiz-Arguelles ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Children And Adolescents ◽  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
High Dose ◽  
Post Transplant

Abstract Patients with high-risk hematological malignancies have a poor prognosis without a hematopoietic stem cell transplant. An HLA- haploidentical donor is available in 95% of the cases, and post-transplant cyclophosphamide permits the use of T-cell replete grafts in settings were ex-vivo manipulation is not available. The experience with HLA-haploidentical HSCT with PBSC and post-tranplant Cy in the pediatric and adolescent population is limited; we report the following experience. We retrospectively collected data on 25 patients (0 to 21 years old) with hematological malignancies, who underwent ambulatory haploidentical HSCT with post-transplant Cy from November 2011 to November 2014. The different conditioning regimens are described in Table 1. All patients received high-dose Cy(50mg/kg) on days +3 and +4. Cyclosporine A (CYA; 6mg/kg/d per os) and mycophenolate mofetil (MMF; 15mg/kg two times daily per os) were started on day +5. MMF was discontinued on day +35 and tapering of cyclosporin started day +90 in the absence of GVHD. All patients received anti-microbial prophylaxis for bacteria, fungal, herpes infection and Pneumocystis jiroveci according to institutional practices. First chimerism was performed at day +30, and second chimerism at day +100. Primary graft failure was defined when neutrophil counts did not exceed 0.5 x 109/L by day +30. Acute and chronic GVHD were graded according to NIH criteria. Patient, donor and stem-cell harvest characteristics are described in Table 1. All patients had high risk hematological malignancies. There were 5 patients who underwent their first transplant on 1st CR, 4 with ALL with high risk cytogenetics and 1 with AML. All other patients were defined as high risk because they were refractory/relapsed. Twenty-three patients (92%) had neutrophil engraftment after a median 17 (7-24) days. Platelet engraftment was observed in 20 (80%) patients after a median of 14.5 (11-23) days, 3 (12%) patients did not have platelet counts below 20,000/mcL. One patient was catalogued as a primary failure for not achieving neutrophil and platelet engraftment by day +30. One patient died before engraftment at day +10 of septic shock. Four patients (16%) died before day +30. The only patient that did not have a complete chimerism, had a diagnosis of AML and 30% of donor cells by day +30, by day +45 relapse of disease was documented. After a median follow-up of 157 days, 13 patients (52%) remain alive, with an estimated 1-year OS of 52% (95%CI: 30.4 - 65.6%).Nine patients (36%) died of complications (mainly infectious) not related to relapse at a median time of 66 days (10-579 days) from stem cell infusion. Nine patients (36%) relapsed in a median time of 105 days (45-288 days); three of those patients died at days +150, +113 and + 370 from transplant. Estimated 1 year event-free survival is 40.2% (95%CI: 41.3 - 75.8%) (Figures 1 and 2). Patients transplanted on 1st CR had a median follow-up of 664 days with an OS and EFS of 80% (4 patients), which was statistically different from the rest of the population (p=0.03) (Figure 3). Among those who engrafted (n=21), 9 cases (42.9%) had grade 2-4 acute GVHD and 4 cases (19%) of grade 3-4 acute GVHD. Three patients (14.3%) developed chronic GVHD, two had mild skin or liver cGVHD. One patient had severe (NIH stage 3) skin cGVHD, she was alive and with a grade 2 cGVHD until last follow up at day +893. Outpatient procedure, HLA-haploidentical HSCT including PBSC as a stem cell source, and post-transplant T-cell in vivo depletion using high-dose cyclophosphamide is feasible in children and adolescents, with acceptable rates of response and GVHD. Table 1. Patient, donor and harvest characteristics Variable N=25 Age, median(range in years) 10 (1-21) Gender, n(%) Male Female 17 (68%) 8 (32%) Diagnosis, n(%) ALL-B ALL-T AML CML 16 (64%) 2 (8%) 5 (20%) 2 (8%) Time from diagnosis to transplant (months) 17.2 (1.9-153.5) Conditioning regimen, n(%) Cy 1500mg/m2 + Flu 75mg/m2 + Bu 9.6mg/kg (IV) Cy 1050mg/m2 + Flu 75mg/m2 + Bu 12 mg/kg (oral) Cy/VP-16/RT Cy/Flu/Mel 16 (64%) 6 (24%) 2 (8%) 1 (4%) Donor, n(%) Mother Father Sister 20 (80%) 3 (12%) 2 (8%) Donor age, median(range in years) 38 (17-49) Infused CD34+ x 106/kg, median(range) 11 (3.2-20) Disclosures No relevant conflicts of interest to declare.

scholarly journals Post-Transplant Cyclophosphamide and Tacrolimus—Mycophenolate Mofetil Combination Governs GVHD and Immunosuppression Need, Reducing Late Toxicities in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors

2021 ◽  
Vol 10 (6) ◽  
pp. 1173
Author(s):  
Fabrizio Carnevale-Schianca ◽  
Daniela Caravelli ◽  
Susanna Gallo ◽  
Paolo Becco ◽  
Luca Paruzzo ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

Combined direct antineoplastic activity and the long-lasting immunological effects of allogeneic hematopoietic cell transplant (HCT) can cure many hematological malignancies, but broad adoption requires non-relapse mortality (NRM) rates and graft-versus-host disease (GVHD) control. Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given with tacrolimus/mofetil mycophenolate (T/MMF) showed activity following allogeneic peripheral blood stem cell transplantation (alloPBSCT). Here, we report the experience of a larger cohort (85 consecutive patients) and expanded follow-up period (03/2011–12/2019) with high-risk hematological malignancies who received alloPBSCT from Human-Leukocyte-Antigens HLA-matched unrelated/related donors. GVHD-prophylaxis was PTCy 50 mg/kg (days+3 and +4) combined with T/MMF (day+5 forward). All patients stopped MMF on day+28 with day+110 = median tacrolimus discontinuation. Cumulative incidences were 12% for acute and 7% for chronic GVHD- and no GVHD-attributed deaths. For surviving patients, the 12, 24, and 36-month probabilities of being off immunosuppression were 92, 96, and 96%, respectively. After a 36-month median follow-up, NRM was 4%; median event-free survival (EFS) and overall survival (OS) had yet to occur. One- and two-year chronic GVHD-EFS results were 57% (95% CI, 46–68%) and 53% (95% CI, 45–61%), respectively, with limited late infections and long-term organ toxicities. Disease relapse caused the most treatment failures (38% at 2 years), but low transplant toxicity allowed many patients (14/37, 38%) to receive donor lymphocyte infusions as a post-relapse strategy. We confirmed that PTCy+T/MMF treatment effectively prevented acute and chronic GVHD and limited NRM to unprecedented low rates without loss of disease control efficacy in an expanded patient cohort. This trial is registered at U.S. National Library of Medicine as #NCT02300571.

scholarly journals Long-Term Mixed Chimerism After Ex Vivo/In Vivo T Cell-Depleted Allogeneic Hematopoietic Cell Transplantation in Patients With Myeloid Neoplasms

2021 ◽  
Vol 11 ◽  
Author(s):  
Leo Ruhnke ◽  
Friedrich Stölzel ◽  
Uta Oelschlägel ◽  
Malte von Bonin ◽  
Katja Sockel ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hematopoietic Cell Transplantation ◽  
Ex Vivo ◽  
Hematopoietic Cell ◽  
Myeloid Neoplasms

In patients who have undergone allogeneic hematopoietic cell transplantation (HCT), myeloid mixed donor chimerism (MC) is a risk factor for disease relapse. In contrast, several studies found favorable outcome in patients with lymphoid MC. Thus far, most studies evaluating MC focused on a short-term follow-up period. Here, we report the first case series of long-term survivors with MC. We screened 1,346 patients having undergone HCT for myeloid neoplasms at our center from 1996 to 2016; 443 patients with data on total peripheral blood mononuclear cells (PBMC)/CD4+/CD34+ short tandem repeat (STR) donor chimerism (DC) and follow-up ≥24 months post-HCT were included. We identified 10 patients with long-term MC (PBMC DC &lt;95% at ≥12 months post-HCT). Median follow-up was 11 years. All patients had received combined ex vivo/in vivo T cell-depleted (TCD) peripheral blood stem cells; none experienced ≥grade 2 acute graft-versus-host disease (GVHD). The mean total PBMC, CD4+, and CD34+ DC of all patients were 95.88%, 85.84%, and 90.15%, respectively. Reduced-intensity conditioning (RIC) was associated with a trend to lower mean total DC. Of note, two patients who experienced relapse had lower CD34+ DC but higher CD4+ DC as compared with patients in continuous remission. Bone marrow evaluation revealed increased CD4+/FOXP3+ cells in patients with MC, which might indicate expansion of regulatory T cells (Tregs). Our results support known predictive factors associated with MC such as RIC and TCD, promote the value of CD34+ MC as a potential predictor of relapse, highlight the potential association of CD4+ MC with reduced risk of GVHD, and indicate a possible role of Tregs in the maintenance of immune tolerance post-HCT.

scholarly journals Aspartate aminotransferase to alanine aminotransferase ratio is associated with frailty and mortality in older patients with heart failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daichi Maeda ◽  
Nobuyuki Kagiyama ◽  
Kentaro Jujo ◽  
Kazuya Saito ◽  
Kentaro Kamiya ◽  
...  
Keyword(s):  
Heart Failure ◽  
Older Patients ◽  
Early Recognition ◽  
Walk Distance ◽  
Failure Data ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
One Year ◽  
Independent Marker

AbstractFrailty is a common comorbidity associated with adverse events in patients with heart failure, and early recognition is key to improving its management. We hypothesized that the AST to ALT ratio (AAR) could be a marker of frailty in patients with heart failure. Data from the FRAGILE-HF study were analyzed. A total of 1327 patients aged ≥ 65 years hospitalized with heart failure were categorized into three groups based on their AAR at discharge: low AAR (AAR < 1.16, n = 434); middle AAR (1.16 ≤ AAR < 1.70, n = 487); high AAR (AAR ≥ 1.70, n = 406). The primary endpoint was one-year mortality. The association between AAR and physical function was also assessed. High AAR was associated with lower short physical performance battery and shorter 6-min walk distance, and these associations were independent of age and sex. Logistic regression analysis revealed that high AAR was an independent marker of physical frailty after adjustment for age, sex and body mass index. During follow-up, all-cause death occurred in 161 patients. After adjusting for confounding factors, high AAR was associated with all-cause death (low AAR vs. high AAR, hazard ratio: 1.57, 95% confidence interval, 1.02–2.42; P = 0.040). In conclusion, AAR is a marker of frailty and prognostic for all-cause mortality in older patients with heart failure.

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