Adaptation of Coagulation and Fibrinolysis in Allogeneic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3023-3023
Author(s):  
Anne Pinomaki ◽  
Liisa Volin ◽  
Lotta Joutsi-Korhonen ◽  
Jussi Oskari Virtanen ◽  
Marja Lemponen labtech ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Thrombin Generation ◽  
Acute Gvhd ◽  
Conditioning Therapy ◽  
Pai 1 ◽  
D Dimer ◽  
Coagulation And Fibrinolysis

Abstract Allogeneic stem cell transplantation (SCT) seems to result in activation of coagulation and fibrinolysis. We characterised the outcome of SCT and graft versus host disease (GvHD) in association with the adaptive mechanisms of coagulation and fibrinolysis. 30 patients given myeloablative conditioning with cyclophosphamide and total body irradiation underwent allogeneic SCT for a hematological malignancy. 19 patients received the transplant from a sibling and 11 from an unrelated donor. GvHD prophylaxis consisted of cyclosporine and methotrexate, and in addition methylprednisolone in case of a sibling donor. Eight patients developed GvHD during the 3-month follow-up. Several coagulation and fibrinolysis activities were serially assessed: antithrombin, protein C (PC), FVIII, prothrombin fragments 1+2 (F1+2), D-dimer, tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1). During the conditioning therapy as an early sign of thrombin generation, F1+2 increased 3-fold and D-dimer 4-fold, compatible with enhanced fibrin turnover. The activity of tPA reached its maximum already before the engraftment and that of PAI-1 diminished accordingly. FVIII increased steadily from normal to reach maximum (up to 273% ±104%, median ±SD, p<0.001) after engraftment. Interestingly, the natural anticoagulant, PC rose (up to 189% ± 63%) in parallel with FVIII, but showed a 5-fold individual variability. After the engraftment the FVIII, PC and antihrombin levels were highly interrelated. Clinically relevant prognostic association was observed between early low PC activity and the appearance of GvHD: the level of PC lower than 90% during the conditioning therapy was associated and even predicted (p=0.007) acute GvHD (OR=16.7). After the transplantation the level of F1+2 over 2.5 nmol/l associated and predicted the non-relapse mortality (p=0.024). Three patients with the largest early thrombin generation all died during a longer follow-up (6–24 months). Also, elevated PAI-1 activity (>10 U/ml) predicted the non-relapse mortality (p=0.013). In conclusion, early activation of coagulation and fibrinolysis is followed by increased FVIII and PC activities in SCT. Early marked thrombin generation and elevated PAI-1 associated with the non-relapse mortality and low PC activity with the appearance of acute GvHD.

Tissue-Factor- and PSGL-1-Bearing Microparticles Are Strong Outcome Predictors in Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2263-2263
Author(s):  
Arne Trummer ◽  
Christiane De Rop ◽  
Michael Stadler ◽  
Stefanie Buchholz ◽  
Arnold Ganser
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Tissue Factor ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Annexin V ◽  
Conditioning Therapy ◽  
Cox Analysis

Abstract Abstract 2263 Poster Board II-240 Objective There is compelling evidence that increased levels of Tissue-factor (TF) and TF-bearing microparticles (MPs) as well as P-selectin and its receptor P-selectin glycoprotein ligand 1 (PSGL-1) play an important role in disease progression, angiogenesis and cancer-related coagulopathy in solid and hematologic malignancies. We therefore hypothesized that numbers of circulating TF- and PSGL-1 bearing MPs might have substantial influence on outcome in allogeneic stem cell transplantation (alloSCT). Patients and Methods Blood samples were obtained from 33 patients with different hematologic diseases (AML=19, ALL=5, CML/MPS=2, CLL/lymphoma=2, myeloma=2, aplastic anemia=2) during the course of alloSCT at distinct time points: at admission (“start”), during conditioning therapy before anti-thymocyte globulin (ATG) infusion (“pre-ATG”), on day 3 of ATG infusion (“during-ATG”), before transplantation (“pre-Tx”), 1 h after transplantation (“post-Tx), on day 1 after transplantation (“d+1post-Tx”) and on day 1 after neutrophil engraftment (“engraftment”). Conditioning regimens included either standard therapies (n=17), FLAMSA (n=11) or other (n=5). GvHD prophylaxis consisted of either CsA/MTX/ATG (n=19), CsA/MMF/ATG (n=11) or CsA/Steroids (n=3). Typical patient and transplant risk factors were included in statistical analysis. Platelet-free plasma (PFP) was obtained by three-step centrifugation, snap-frozen in liquid nitrogen and stored at -80°C. After thawing, 50μl of PFP were resuspended in Annexin V binding or control buffer and labeled with 1μl Annxin V-Cy5 and 0.5μg of CD142-FITC (TF), CD162-FITC (PSGL-1) or isotype control. In flow cytometry MPs were gated by size (<1μm) and Annexin V positivity and Trucount tubes® were used for MP enumeration. Results Mean follow-up time was 759 (10-1305) days. 17 (51.5%) patients died, 9 due to TRM (27.3%), and 12 (36.4%) had recurrence or progression during follow-up. Median overall survival (OS) was 815 days, median disease-free or progression survival (DFS/PFS) 440 (10-1272) days and median time to progression (TTP) 365.5 (130-1183) days. MP counts are shown in table 1. There was a significant reduction (p<0.05) for Annexin V- and PSGL-1-MPs from “start” to “pre-Tx” and an increase after transplantation while TF-MPs had significant higher numbers at “d+1post-Tx” compared to “start” values. Univariate Cox analysis identified TF-MPs at “start” (p=0.011, HR=1.006 per 1 MP/μl) and “pre-ATG” (p=0.004, HR=1.011) to be significantly associated with OS. When corrected for known risk factors, TF-MPs “pre-ATG” remained the only independent predictive parameter for OS in multivariate Cox analysis s(p=0.036, HR 1.022). A cut-off value was determined for stratification of patients by calculating the AUC of a ROC–curve (p=0.030, AUC 0.762). Thus, Patients with TF-MP values >140/μl showed a significantly shorter survival time (p=0.007; mean OS: 469.4±160.0 vs. 1038.5±110.3 days). Same was done for DFS/PFS and again TF-MP values >140/μl were predictive of worse DFS/PFS (p=0.020, HR=3.61) in multivariate Cox regression with a shortened DFS/PFS (p=0.013; mean: 350.9±113.8 vs. 852.5±129.6 days). These findings were caused by an increased treatment-related mortality (TRM) with a cumulative incidence at 1 year of 55.5% vs. 13.3% for corresponding TF-MP groups (p=0.029). TRM was caused by infection (n=4), VOD (n=2) or other reasons (n=3). There was no significant association with relapse or acute GvHD. Furthermore, we found PSGL-1-MP counts below 250/μl “post-Tx” (and on “engraftment”) to be a significant predictor of relapse/progression (p=0.044, HR=4.91) with a cumulative incidence at 3 years of 81% (95%-CI: 61.9-100) vs. 11.1% (95%-CI: 1.8-70.5) and a mean TTP of 602±106.1 vs. 1140±104.5 days (p=0.027). Conclusions TF-bearing MPs before and during conditioning therapy are prognostic markers of OS and DFS/PFS due to increased TRM while PSGL-1 bearing MPs after transplantation and at engraftment predict relapse/progression and TTP. Course of MP counts suggests increased TF-MP release by monocytes, endothelial and stromal cell while significant differences in PSGL-1-MPs might rather be graft-related. Disclosures: Trummer: CSL Behring: Research Funding.

Allogeneic Stem Cell Transplantation of Mantle Cell Lymphoma - Results of the Prodpective Trials OSHO #060 and OSHO #074

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2014-2014
Author(s):  
William H Krüger ◽  
Carsten Hirt ◽  
Nadezda Basara ◽  
Dietger Niederwieser ◽  
Gerhard Behre ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Allogeneic Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Acute Gvhd ◽  
De Novo ◽  
Cell Lymphoma ◽  
Mantle Cell

Abstract Abstract 2014 Introduction: Mantle cell lymphoma (MCL) has a poor prognosis under conventional therapy. Allo-SCT after conventional or reduced-intensity conditioning is here a promising approach. Methods: Two prospective trials were conducted to investigate the efficacy of chemotherapy-based conditioning followed by allo-SCT for treatment of MCL: Trial #074 was open for patients with de-novo MCL and #060 for patients requiring salvage therapy. At least a pR to (re)-induction therapy was mandatory for proceeding to allo-SCT. Conditioning consisted of treosulfan (12g/m2) and fludarabin (150mg/m2). Busulphan (16mg/kg) and cyclophosphamide (120mg/kg) was optional for younger patients. ATG was given prior to mismatched or mud SCT. Assessment of minimal residual disease was performed with real-time PCR-amplification of t(11;14) or of specific CDR3-sequences. Results: 39 patients have been recruited into both trials (#060: n=15, #074: n=24). 31 patients are male and 8 are female with a median age of 59y (33–69). In de-novo patients the median MIPI was 5 (2–9). Salvage patients were pre-treated with 8 (6–13) cycles chemotherapy. (Re)-Induction prior to TX consisted mainly of R-CHOP or R-DHAP. 33 patients proceeded to allo-TX from mrd or mud. 2 patients died from progressive disease prior to TX, 1 patient had no suitable stem cell donor, in one case the diagnosis was revised and 2 patients were withdrawn. 26 patients (79%) were conditioned with Treo/Flu and 7 (21%) with Bu/Cy. 76% (n=25) of patients received a graft from an unrelated donor. Toxicity was moderate and incidence of acute GvHD was 51%. The median follow-up after allogeneic stem cell transplantation was 18 months with a range from 0,26 to 113,7 months. The median disease-free and median overall survivals have not been reached. Three patients have relapsed after transplantation between 5,4 and 26,7 months after transplantation. One of these suffered from blastic variant of MCL. 26 patients are alive with a median KI of 100% (range 50%-100%) after SCT with a median follow-up of 18 months (0,3–114) without differences between both trials (p=0,67). 6 patients have died from infections and cerebral bleeding (n=1) and one from infection related to an acute GvHD IV° due to DLI for relapse (blastic variant) ten months after SCT in CR of MCL. Molecular analyses showed a 2–4log reduction of circulating lymphoma cells after chemotherapy alone. Blood became negative by qPCR after allo-SCT in all 5 patients analysed so far. An intermediate increase of circulating lymphoma cells in 4 patients was successfully treated by rituximab, withdrawal of Cy-A and DLI. Conclusion: Allo-SCT is a standard salvage therapy for suitable patients and an option for patients with de-novo MCL. Long-term remissions can be reached and negativity of mrd analyses by qPCR strongly supports curative potential of allo-SCT. GvL-effect has curative potential even in the case of relapsed blastic variant of MCL. Disclosures: Sayer: Medac:.

Allogeneic Stem Cell Transplantation Following Reduced Intensity Conditioning Regimen for Treatment of Refractory Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4425-4425
Author(s):  
Jieling Jiang ◽  
Chun Wang ◽  
Shike Yan
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity ◽  
Related Mortality

Abstract Objective To evaluate the efficacy of allogeneic stem cell transplantation (allo-HSCT) following reduced intensity conditioning (RIC) regimen in the treatment of relapsed and refractory leukemia. Methods Fourteen patients with acute myeloid leukemia, eleven patients with acute lymphocyte leukemia and two patients with chronic myeloid leukemia blast phase received allo-HSCT following RIC regimen consisting of fludarabine and small or moderate dose total body irradiation (TBI). Patients received mobilized peripheral stem cell from HLA matched siblings (n=11), at least 5/6 matched unrelated donor (n=10) or haploidentical related donor (n=6). All patients were in advanced disease before transplantation. Graft versus host disease (GVHD) prophylaxis program consist of cyclosporin A plus mycophenolate mofetil or short-term methotrexate, or these three drugs combination; CD25 monoclone antibody and ATG were also used in patients with unrelated or haploidentical donors. Results Sustained engraftment was attained in 22 patients, the median time to ANC &gt;0.5×109/L was 13 days (range: 11~17days), and the median time to BPC &gt; 50×109/L was 19 days (range: 12~42days). Detected by short tandem repeat (STR)-PCR, complete donor chimerism was comfirmed in 20 patients with a median of 14days (range: 7~70 days). With a median follow-up of 9 months (range, 1~44months), the incidences of acute GVHD and chronic GVHD were 50% (11/22) and 41.2% (8/17) respectively. The transplant related mortality was 25.9% (7/27), mainly from graft failure (n=4), intracranial hemorrhage (n=1), acute GVHD (n=1), and severe infection(n=1). At the time of last follow up, ten patients relapsed, eleven patients were alive and leukemia free. Probabilities of overall survival for AML and ALL patients were (51.9±13.4)% and (32.7±15.0)% at 2 years, respectively. It seems that AML patients had a better outcome than ALL patients, but there was no significant difference (289). Conclusion Allogeneic stem cell transplantation following fludarabine and TBI based RIC regimen could be used in the treatment of relapsed and refractory leukemia with well tolerance and low transplant related mortality from which patients may be benefit.

scholarly journals The Burden of Survivorship on Hematological Patients—Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5640
Author(s):  
Michael Oertel ◽  
Jonas Martel ◽  
Jan-Henrik Mikesch ◽  
Sergiu Scobioala ◽  
Christian Reicherts ◽  
...  
Keyword(s):  
Stem Cell ◽  
Side Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Total Body Irradiation ◽  
Whole Body ◽  
Total Body

Total body irradiation is an effective conditioning modality before autologous or allogeneic stem cell transplantation. With the whole body being the radiation target volume, a diverse spectrum of toxicities has been reported. This fact prompted us to investigate the long-term sequelae of this treatment concept in a large patient cohort. Overall, 322 patients with acute leukemia or myelodysplastic syndrome with a minimum follow-up of one year were included (the median follow-up in this study was 68 months). Pulmonary, cardiac, ocular, neurological and renal toxicities were observed in 23.9%, 14.0%, 23.6%, 23.9% and 20.2% of all patients, respectively. The majority of these side effects were grades 1 and 2 (64.9–89.2% of all toxicities in the respective categories). The use of 12 Gray total body irradiation resulted in a significant increase in ocular toxicities (p = 0.013) and severe mucositis (p < 0.001). Renal toxicities were influenced by the age at transplantation (relative risk: 1.06, p < 0.001) and disease entity. In summary, total body irradiation triggers a multifaceted, but manageable, toxicity profile. Except for ocular toxicities and mucositis, a 12 Gray regimen did not lead to an increase in long-term side effects.

scholarly journals Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center

2021 ◽  
Vol 27 ◽  
Author(s):  
A. Kopińska ◽  
A. Koclęga ◽  
A. Wieczorkiewicz-Kabut ◽  
K. Woźniczka ◽  
D. Kata ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Disease Status ◽  
Term Survival ◽  
Entire Cohort

Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach.Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting.Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18–44) underwent allo-SCT between 2002 and 2020.Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%.Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.

scholarly journals Pilot Study on Frailty and Functionality on Routine Clinical Assessment in Allogeneichematopoietic Cell Transplantation to Predict Outcomes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 380-380 ◽  
Author(s):  
Maria Queralt Salas ◽  
Eshetu G Atenafu ◽  
Ora Bascom ◽  
Leeann Wilson ◽  
Arjun Law ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pilot Study ◽  
Stem Cell Transplantation ◽  
Grip Strength ◽  
Cell Transplantation ◽  
Waiting Time ◽  
Acute Gvhd ◽  
Number Of Patients ◽  
And Function

Introduction: Frailty can adversely affect the outcomes of allogeneic hematopoietic stem cell transplantation (alloHSCT) but is difficult to measure in busy transplant clinics. The limited published studies have used dedicated trained persons and comprehensive geriatric assessment (GA) tools, which are time consuming (Muffly LS, Haematologica 2014; Holmes HM, J Geriatr Oncol 2014; Rodrigues M, J Geriatr Oncol 2019). The difficulty in application of GA tools by transplant clinicians, residents and nurses in their clinics has resulted in low adoption rates in routine practice. At our center we adopted selected tests for frailty and function which could be conducted during pre-transplant consultation in a busy clinic, without extra waiting time for patients, and using existing staff. The Timed up and Go test (TUGT) was adopted as it could be done in any closed clinic room, without need for a corridor. Thus it was considered safer than a gait speed test and was even applicable to patients in "isolation". We aim to share a preliminary analysis of the applicability and correlation between our selected frailty assessment with transplant outcomes and complications. Methods: Patients referred for transplant underwent the following assessments conducted by different providers. All ages were included. Relevant tests and source of data are as follows: Frailty and function by clinician evaluating (a) Clinical Frailty scale (CFS) with 9 points based on clinical judgement (Rockwood 2005) (b) Lawton's Instrumental activities of daily living (IADL). Objective physical performance by nursing BMT coordinator using (a) TUGT and (b) Grip strength using hydraulic "Jamar" hand dynamometer conducted in clinic room at time of documentation. Self assessment by patient completing (a) Self-rated health (SRH) question and (b) a question on falls. Blood tests (a) CRP (b) Albumin. The present study is a single center prospective observational study. Patients who did not proceed to transplant were excluded. Ninety-six consecutive adult allo-HSCT patients were eligible for the present analysis, updated on July 2019. The parameters were individually correlated with overall survival (OS), non-relapse mortality (NRM), cumulative incidence (cum.Inc) of acute GVHD, median time of transplant hospitalization and readmissions. Multivariate analysis was not performed in this pilot study due to limited number of patients and low frequency of adverse events. Results: Baseline characteristics and main post-transplant information are noted in Table 1. Median follow up of cohort was 5 months. Table 2 shows the main outcomes (with normal values). For the entire cohort the median OS at 6 months was 73.9% (range 61.7-82.8), NRM at day+100 was 8.7% (range 2.6-14.7), Cum.Inc of Acute GVHD 41.1% (range 30.1-52.1), Cum.Inc gr II-IV acute GVHD was 25.7% (range 15.6-35.9). Relapse occurred in 8 cases (8.3%) and deaths in 23 (23.9%). A TUGT of more than 10 seconds and raised CRP predicted poor OS (p&lt;0.05). Abnormal TUGT, SRH question score of &lt;A (excellent), lower albumin levels and raised CRP levels correlated with high NRM (p&lt;0.05). A Clinical Frailty Score of more than 2, limitations of 1 or more IADLs, Grip strength below normal for age and sex, TUGT &gt;10 seconds, SRH question &lt;A, and lower albumin level were significant predictors for a longer median duration of transplant hospitalization. No frailty or functionality parameter correlated significantly with the Cum.Inc of any grade of acute GVHD, grade II-IV acute GVHD or the risk of rehospitalization after alloHSCT. Conclusions: Our pilot study shows that with selected brief tools, frailty and functionality can be assessed as part of routine clinical practice in allogeneic-stem cell transplantation in all age groups without extra waiting time for patients or additional human resources. TUGT is a useful prognostic tool which can be conducted in a clinic room and correlates with OS, NRM, and duration of hospitalization. Larger number of patients and longer follow-up will help to evaluate the different assessment modalities as prognostic tools in allo-HSCT and their wider applicability. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Gilead: Honoraria; Celgene: Honoraria; Therakos: Honoraria.

scholarly journals Long-Term Outcome of Allogeneic Stem Cell Transplantation in Patients with Paroxysmal Nocturnal Hemoglobinuria with or without Aplastic Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2195-2195
Author(s):  
Sung-Eun Lee ◽  
Sung Soo Park ◽  
Young-Woo Jeon ◽  
Jae-Ho Yoon ◽  
Byung Sik Cho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Pnh Clone

Abstract Background: Although recently, Eculizumab, humanized monoclonal antibody directed against complement component C5, has used increasingly for the patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH), allogeneic stem cell transplantation (allo-SCT) can be curative treatment option especially for PNH patients with combined aplastic anemia (AA). The aim of the present study was to evaluate long-term outcome of allo-SCT in patients with AA/PNH. In addition, patients with classic PNH who underwent allo-SCT in the pre-eculizumab era were also evaluated. Methods: Total of 33 patients with PNH clones underwent allogeneic SCT at our institution between Jan 1998 and Jan 2016. Among them, seven patients had classic PNH and 26 patients with cytopenia had AA/PNH (with bone marrow evidence of a concomitant AA). Results: There were 21 male and 12 female patients with a median age of 34 years (range, 13-56 years). Pre-transplant GPI-AP deficient neutrophils and erythrocytes were 5.6% (0-92) and 21% (0-98.5), respectively. Median white blood cell, absolute neutrophil count, hemoglobin, and platelet at transplant were 2.4×109/L, 0.8×109/L, 7.7 g/dL, and 27×109/L, respectively. Median LDH level was 727 U/L (232-7721 U/L) and 19 (58%) patients had LDH ≥1.5x upper limit of normal. Classic PNH (n=7) and AA/PNH [SAA (n=15), VSAA (n=9), or non-SAA (n=2)] received SCT from HLA-matched sibling (MSD, n=24), unrelated (URD, n=7), or haplo-identical donor (Haplo-SCT, n=2). Since 2003, the conditioning regimen for MSD-SCT was changed from Busulfex (12.8 mg/kg) + cyclophosphamide (CY, 120 mg/kg) to fludarabine (180 mg/m2) + CY (100 mg/kg) + rATG (10 mg/kg). The conditioning regimen for URD-SCT and Haplo-SCT were TBI (800 cGy) + CY (100-120 mg/kg) ± rATG (2.5 mg/kg) and TBI 600cGy + Fludarabine (150 mg/m2) + rATG (5 mg/kg), respectively. After a median follow-up of 57 months (range 6.0-151.3), the 5-year estimated OS rates were 87.9 ± 5.7%. Four patients died of treatment-related mortality (TRM), including acute GVHD (n=1), pneumonia (n = 2), and cerebral hemorrhage (n=1), respectively. Except one patient with early TRM, 32 patients engrafted. Two patients who experienced delayed graft-failure received second transplant and recovered. The cumulative incidence of acute GVHD (≥grade II) and chronic GVHD was 27.3 ± 7.9% and 18.7 ± 7.0%, respectively. Among 25 patients with available follow-up data, PNH clone disappeared at median 3.0 months (range 0.7-45.5) after SCT and reemerging of PNH clones was observed in two patients; one patient showed re-appearance of 2.6% GPI-negative neutrophils at 12 months without PNH symptoms, but disappeared again at 21 months. Another patient suffered from labile graft and received a booster with peripheral blood stem cells. Conclusion: This study showed that long-term transplant outcome in patients with AA/PNH were comparable to that of allogeneic SCT in SAA (the 3-year estimated OS rates were 92.7 and 89 % for MSD-SCT and URD-SCT, respectively) at our institution (ASH Annual Meeting Abstracts 2012;120:4151). Reduced-intensity conditioning regimen was sufficient for the eradication of PNH clone in allogeneic SCT. Therefore, application of allogeneic SCT should be considered in PNH patients with AA in case of availability of well matched donor. Disclosures No relevant conflicts of interest to declare.

scholarly journals Preconditioning Serum Levels of Endothelial Cell-Derived Molecules and the Risk of Posttransplant Complications in Patients Treated with Allogeneic Stem Cell Transplantation

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Roald Lindås ◽  
Tor Henrik Andersson Tvedt ◽  
Kimberley Joanne Hatfield ◽  
Håkon Reikvam ◽  
Øystein Bruserud
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Serum Levels ◽  
Population Based ◽  
Biologically Active ◽  
Cell Adhesion Molecule 1

Endothelial cells are involved in the pathogenesis of acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. These cells express several molecules that can be detected as biologically active soluble forms; serum levels of these molecules may thereby reflect the functional status of endothelial cells. Furthermore, acute GVHD is an inflammatory reaction and endothelial cells function as local regulators of inflammation. We therefore investigated whether differences in preconditioning/pretransplant serum levels of endothelium-expressed molecules (i.e., endocan, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin) were associated with a risk of posttransplant GVHD. Our study should be regarded as a population-based study of consecutive and thereby unselected patients (n=56). Analysis of this pretreatment endothelium biomarker profile by unsupervised hierarchical clustering identified a subset of patients with increased early nonrelapse mortality. Furthermore, low endocan levels were significantly associated with acute GVHD in the liver and gastrointestinal tract, whereas high VCAM-1 levels were associated with acute GVHD in the skin only. Our study suggests that the preconditioning/pretransplant status of endothelial cells (possibly through altered trafficking of immunocompetent cells) is important for the risk and the organ involvement of later acute GVHD.

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