Screening With Spirometry Is A Useful Predictor Of Later Development Of Non-Infectious Pulmonary Syndromes In Patients Undergoing Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4603-4603
Author(s):  
Thompson A Philip ◽  
Andrew B M Lim ◽  
Mark Tacey ◽  
Ramzi Hijazi ◽  
Ashley P. Ng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Lung Function ◽  
Stem Cell Transplantation ◽  
Airflow Obstruction ◽  
Disease Relapse ◽  
One Year ◽  
Fixed Airflow Obstruction ◽  
Median Change

Background Non-infectious pulmonary syndromes (NIPS) frequently complicate allogeneic stem cell transplantation (alloSCT). The most common and serious is the bronchiolitis obliterans syndrome (BOS), characterized by irreversible fixed airflow obstruction, impaired quality of life and a high mortality. Treatment for established symptomatic disease is relatively ineffective. Although changes in spirometry parameters at day 80 have been shown to correlate with poorer lung function at one year, no screening test has been proven to clearly predict for the development of NIPS. We sought to determine whether early changes in spirometry parameters predict later development of NIPS. Secondary objectives were to determine pre-transplant predictors of NIPS and the impact of NIPS on relapse, treatment-related mortality (TRM) and survival. Methods Spirometry and DLCO were performed pre-alloSCT, at day 100 (D100) and one year post-alloSCT. We retrospectively analyzed spirometry, CT and bronchoalveolar lavage results in consecutive patients having alloSCT from 2004-2010 to identify cases of NIPS. Cases of BOS and cryptogenic organizing pneumonia (COP) were defined as per published guidelines (NIH consensus guidelines, 2005). Spirometry trends and baseline variables were compared between patients with and without NIPS to identify early predictors and risk factors for NIPS. Results Pulmonary function 257 patients underwent allo-SCT during the study period. 235 survived to D100 and were thus assessable for chronic GVHD (cGVHD) and NIPS. Of these, 23 (9.8%) developed NIPS, 18 with BOS and 5 with COP. Median time of onset was day 367 (IQR 144-544 days). All but one case developed prior to two years post-alloSCT. Change in FEV1.0 (ΔFEV1.0), was the best predictor of later NIPS development, while change in pulmonary diffusion capacity for carbon monoxide was not predictive. Median ΔFEV1.0 from pre-transplant to D100 in patients later developing NIPS was -12% (IQR -25% to -1%) vs -1% (IQR -7% to +6%) in those who did not, p=0.002. From pre-transplant to 1 year, it was -19% (IQR -37% to -6%) vs -3% (-10% to +4%), respectively, p<0.001. Median FEV1.0 at diagnosis was 58% predicted (IQR 46-71%). Once fixed airflow obstruction was established, progressive deterioration in lung function with time was the rule; median change in FEV1.0 during follow-up, post-diagnosis of NIPS, was -2% per annum (IQR -7 to 0%). Median follow-up duration post-diagnosis of NIPS was 1 year, range 0-6 years. For those with BOS and >6 months of follow-up, median change in FEV1.0 per year during follow-up was -8% (IQR -14% to -2%). In contrast, 4 of the 5 patients with COP had substantial improvement in FEV1.0 (11-36%) with normalization of FEV1.0 in 3 of these 4. Pre-transplant risk factors Busulfan-based, but not total body irradiation (TBI)-based conditioning increased the risk of NIPS [OR=8.87, 95%CI 3.33-23.63, p<0.001]. No cases of NIPS were seen in 53 patients who received in vivo T-cell depletion with Thymoglobulin as part of their conditioning (p<0.0001). Survival At a median follow-up of 44 months, overall survival was 59.1%. There was a trend towards increased all-cause mortality in those patients developing NIPS [HR = 2.02, 95%CI 0.92-4.44, p=0.08] and an increase in TRM [HR = 5.96, 95%CI 2.14-16.62, p=0.001], with eight patients (35%) with NIPS experiencing TRM. No statistically significant difference in disease relapse was seen between those with and without NIPS [HR = 0.24, 95%CI 0.03–1.80], although only one patient with NIPS experienced disease relapse. This may reflect the small numbers of patients with NIPS. Conclusions Spirometry is a potentially useful screening test for identification of pre-symptomatic NIPS. We recommend 3-monthly spirometry surveillance for up to two years post-transplant, given the moderately severe obstruction at diagnosis (median FEV1.0 58% predicted) and the incidence of 50% of cases between one and two years post-allo-SCT. Our findings require prospective validation to identify patients in whom earlier intervention may potentially modify the natural history of this disease. Disclosures: No relevant conflicts of interest to declare.

Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gizem Guner Ozenen ◽  
Serap Aksoylar ◽  
Damla Goksen ◽  
Salih Gozmen ◽  
Sukran Darcan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Life Quality ◽  
Control Group ◽  
Hematopoietic Stem

Abstract Objectives The early and late complications after hematopoietic stem cell transplantation (HSCT) determine the patients’ prognosis and life quality. We aim to determine the metabolic syndrome development frequency after HSCT in children to find out the risk factors and compare them with healthy adolescents. Methods Thirty-six children who underwent HSCT at least two years ago were analyzed prospectively and cross-sectionally. Our study included 18 healthy children between the ages of 11 and 17 as a control group. All of the cases were assessed in terms of metabolic syndrome (MS) through the use of Modified WHO Criteria. Results The patients’ median age was 10.6 (5.1–17) years, the median time of follow-up after HCST was 4.1 (2–13.5) years and 70% were male. Two cases were diagnosed with MS (5.6%). When considered in terms of the sub-components of MS, 2 cases (5.6%) were found to have obesity, 17 cases (47%) abnormal glucose tolerance, 11 cases (30.7%) dyslipidemia, and 3 cases (8.6%) hypertension. The MS rate was not different when compared with the 11–17 year-old healthy control group (0 vs. 11%, p=0.48). Myeloablative conditioning regimen (65 vs. 20%) and the increased age at which HSCT was performed were considered to be risk factors in terms of insulin resistance (p=0.025 and 0.002). Conclusions Age and conditioning regimens were found to be the risk factors for insulin resistance development. The long-term follow-up of the cases who had undergone HSCT in childhood in terms of MS and its sub-components is important in order to increase life quality.

P1825ANALYSIS OF LATE RENAL COMPLICATIONS AND RISK FACTORS IN CHILDREN WITH HEMATOPOIETIC STEM CELL TRANSPLANTATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anar Gurbanov ◽  
Bora Gülhan ◽  
Barış Kuşkonmaz ◽  
Fatma Visal Okur ◽  
Duygu Uçkan Çetinkaya ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Renal Complications

Abstract Background and Aims The aim of the study is to investigate the incidence and risk factors of hypertension (HT) and chronic kidney disease (CKD) in patients who had hematopoietic stem cell transplantation (HSCT) during their childhood. Method Patients who had HSCT between January 2010-2019 with a minimum follow-up period of 6 months were included in the study. Data regarding renal complications were collected from the medical records of the patients. Guidelines of European Society of Hypertension (ESH) and American Academy of Pediatrics (APA) were used for the evaluation of hypertension. 24-hr ambulatory blood pressure monitoring (ABPM) was performed in children older than 5 years of age (68 patients). Ambulatory hypertension is diagnosed when systolic and/or diastolic blood pressure (BP) load is higher than 25%. Ambulatory prehypertension is diagnosed when mean systolic and/or diastolic BP is less than 95th percentile with systolic and/or diastolic BP load higher than 25%. Results A total of 72 patients (41 males and 31 females) were included in the study. The mean age of the patients at last visit was 10.8±4 years. ABPM revealed ambulatory HT in 6 patients (8.8%) and ambulatory prehypertension in 12 patients (17.6%). Office BP revealed HT in 3 patients (4.2%) and increased BP in four patients (5.6%) according to APA guideline (2017). In cohort, 12 patients with normal office BP (according to APA guideline) had ambulatory prehypertension or hypertension with ABPM. Office BP revealed HT in 1 patient (1.4%) and high-normal BP in 3 patients (4.2%) according to ESH guideline. In cohort, 15 patients with normal office BP (according to ESH guideline) had ambulatory prehypertension or hypertension with ABPM (Table 1). After a mean follow-up period of 4.4±2.5 years, CKD developed in 8 patients (11.1%). Patients with chronic graft-versus-host disease, with HLA-mismatched HSCT and/or transplantation of peripheric or cord blood hematopoietic stem cells had increased risk of CKD (p=0.041, p=0.033 and p=0.002, respectively). Conclusion Patients with HSCT should be regularly followed for the development of HT and ABPM should be used on regular basis. Patients with risk factors should be closely monitored for the development of CKD.

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.

scholarly journals Outcomes of Autologous Stem Cell Transplantation in Elderly Mexican Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5812-5812
Author(s):  
Brenda Lizeth Lizeth Acosta-Maldonado ◽  
Liliana Rivera-Fong. ◽  
Juan Francisco Zazueta Pozos. ◽  
Jaime Eduardo Dulón Tarqui. ◽  
José Guadalupe Ríos. ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Neutropenic Fever ◽  
The Other ◽  
Line Treatment ◽  
Disease Relapse ◽  
One Year

Abstract Introduction Autologous hematopoietic stem cell transplantation (ASCT) is a treatment option for long-term remission in patients with multiple myeloma and recurrent non-Hodgkin´s lymphoma (NHL). The eligibility for ASCT is based on a risk-benefit assesssment of the disease, age has not been considered an exclusion criteria for ASCT where treatment related mortality are relatively low. The treatment-related morbidity is associated with toxicity of condition regimen and infections associated with the degree of immune deficiency. Outcome in elderly patients with multiple myeloma and recurrence of Hodgkin´s lymphomas with chemosensitive illness in ≥ 60 years patients undergo ASCT are limited and contradictory. For this reason the aims of the present study was to reviewed to identify patient with multiple myeloma and non-Hodgkin lymphoma undergoing ASCT at 60 or greater and describe the clinical data and outcome. Method: This work was a retrospective transversal study, 24 patients older than 60 years was enrolled and all of them were undergo ASCT al Instituto Nacional de Cancerologia, Mexico from 2005 to 2015. We assessed previous comorbidities, treatment lines, response prior to transplantation, treatment response, relapse free-survived and global survival, it was considered from the transplantation day until last visit at the hospital. Results Twenty-four patients were assessed, all were ≥60 years at the transplant moment. 16 of them had diagnostic of multiple myeloma and 8 with Non-Hodgkin's lymphoma (NHL). For the multiple myeloma group the median of age was 66 years (60-70 years), the 81% was male. At the transplant moment, two people in that group had hypertension, one had diagnosis of Diabetes Mellitus Diabetes II and the another did not have any other illness. At the transplant moment 62.5% of the patients had been treated with only one line treatment and 37.5% had been received two treatment lines. On the other hand, at the transplant moment 50% of the patients had completed response, 12% had partial response, 31.26% had very good partial responses and 6.25% had illness progression. Multiple myeloma patient was conditioned with melphalan 200mg/m2 in 95%. Neutrophils recovery was at 12 days. Fourty-three percent of the patient required transfusion. Neutropenic fever was presented in 43% of the patient. Fifty percent got completed response after ASCT and 20% with progression disease. Relapse disease was in 31% and mortality was 6.25%, there was not mortality associated with the process and 44% is alive without illness (Table 1). In patients with multiple myeloma the OS at two year was 100% and at three years 86%; for NHL patients OS at one year was 67% and at two years 33%. . For the NHL group the median of age was 67 years (61-72 years), the 50% was male, one person in that group had HTA at transplant moment, another one had diagnosis of MDII, another one had rheumatology disease and another one had long disease, and the other four did not have any other diseases. At the transplant moment 37.5% of the patients had been treated with only one line treatment, 37.5% had been received two treatment lines and 25% had been received three treatment lines. On the other hand, at the transplant moment 87.5% of the patients had completed response and 12.5% had partial response. NHL patients were conditioned with PEAM (cisplatin, etoposide, cytosine arabinoside and melphalan) 25%, Rituximab-PEAM in 62.5% and one patient with fludarabine with cyclophosphamide (FLUCY). Neutrophils recovery was at 12 days. Fourty-three percent of the patient required transfusion. Neutropenic fever was presented in 43% of the patient. Fifty percent got completed response after ASCT and 20% with progression disease. Relapse disease was in 31% and mortality was 6.25%, there was not mortality associated with the process and 44% is alive without illness (Table 1) For lymphoma, the relapse-free survival at one year 48.6%. For patients with multiple myeloma, the free illness survival at one year was 85.7%, at two years 77.9% and at four year 58.4%. Conclusion Autologous stem cell transplantion in older people is a good option for treatment without mortality asociated at process. The complications like neutropenic fever and transfusional requirement are similar with younger patients. In our population, age is not a limit to offer a treatment with high dose of chemotherapy and autologous. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cell Competition between Wild-Type and JAK2V617F Mutant Cells Prevents Disease Relapse after Stem Cell Transplantation in a Murine Model of Myeloproliferative Neoplasm

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1468-1468
Author(s):  
Haotian Zhang ◽  
Melissa Castiglione ◽  
Lei Zheng ◽  
Huichun Zhan
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Disease Relapse ◽  
Wild Type ◽  
Cell Competition ◽  
Donor Cells ◽  
Significant Difference ◽  
Mutant Cells

Abstract Introduction Disease relapse after allogeneic stem cell transplantation is a major cause of treatment-related morbidity and mortality in patients with myeloproliferative neoplasms (MPNs). The cellular and molecular mechanisms for MPN relapse are not well understood. In this study, we investigated the role of cell competition between wild-type and JAK2V617F mutant cells in MPN disease relapse after stem cell transplantation. Methods JAK2V617F Flip-Flop (FF1) mice (which carry a Cre-inducible human JAK2V617F gene driven by the human JAK2 promoter) were crossed with Tie2-cre mice to express JAK2V617F specifically in all hematopoietic cells and vascular endothelial cells (Tie2FF1), so as to model the human diseases in which both the hematopoietic stem cells and endothelial cells harbor the mutation. Results To investigate the underlying mechanisms for MPN disease relapse, we transplanted wild-type CD45.1 marrow directly into lethally irradiated Tie2FF1 mice or age-matched control mice(CD45.2). During a 6-7mo follow up, while all wild-type control recipients displayed full donor engraftment, ~60% Tie2FF1 recipient mice displayed recovery of the JAK2V617Fmutant hematopoiesis (mixed donor/recipient chimerism) 10 weeks after transplantation and developed a MPN phenotype with neutrophilia and thrombocytosis, results consistent with our previous report. Using CD45.1 as a marker for wild-type donor and CD45.2 for JAK2V617F mutant recipient cells, we found that the wild-type HSCs (Lin -cKit +Sca1 +CD150 +CD48 -) were severely suppressed and the JAK2V617F mutant HSCs were significantly expanded in the relapsed mice; in contrast, there was no significant difference between the wild-type and mutant HSC numbers in the remission mice. (Figure 1) Cell competition is an evolutionarily conserved mechanism in which "fitter" cells out-compete their "less-fit" neighbors. We hypothesize that competition between the wild-type donor cells and JAK2V617F mutant recipient cells dictates the outcome of disease relapse versus remission after stem cell transplantation. To support this hypothesis, we found that there was no significant difference in cell proliferation, apoptosis, or senescence between wild-type and JAK2V617F mutant HSPCs in recipient mice who achieved disease remission; in contrast, in recipient mice who relapsed after the transplantation, wild-type HSPC functions were significantly impaired (i.e., decreased proliferation, increased apoptosis, and increased senescence), which could alter the competition between co-existing wild-type and mutant cells and lead to the outgrowth of the JAK2V617F mutant HSPCs and disease relapse. (Figure 2) To understand how wild-type cells prevent the expansion of JAK2V617F mutant HSPCs, we established a murine model of wild-type and JAK2V617F mutant cell competition. In this model, when 100% JAK2V617F mutant marrow cells (from the Tie2FF1 mice) are transplanted alone into lethally irradiated wild-type recipients, the recipient mice develop a MPN phenotype ~4wks after transplantation; in contrast, when a 50-50 mix of mutant and wild-type marrow cells are transplanted together into the wild-type recipient mice, the JAK2V617F mutant donor cells engraft to a similar level as the wild-type donor cells and the recipient mice displayed normal blood counts during more than 4-months of follow up. In this model, compared to wild-type HSPCs, JAK2V617F mutant HSPCs generated significantly more T cells and less B cells in the spleen, and more myeloid-derived suppressor cells (MDSCs) in the marrow; in contrast, there was no difference in T, B, or MDSC numbers between recipients of wild-type HSPCs and recipients of mixed wild-type and JAK2V617F mutant HSPCs. We also found that program death ligand 1 (PD-L1) expression was significantly upregulated on JAK2V617F mutant HSPCs compared to wild-type cells, while PD-L1 expression on mutant HSPCs was significantly decreased when there was co-existing wild-type cell competition. These results indicate that competition between wild-type and JAK2V617F mutant cells can modulate the immune cell composition and PD-L1 expression induced by the JAK2V617F oncogene. (Figure 3) Conclusion Our study provides the important observations and mechanistic insights that cell competition between wild-type donor cells and JAK2V617F mutant recipient cells can prevent MPN disease relapse after stem cell transplantation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Increased Mortality in Patients with Autoimmune Hemolytic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2512-2512
Author(s):  
Meng Wang ◽  
Wenjia Wang ◽  
Ayesha Abeywardane ◽  
Malinthi Adikarama ◽  
Donal McLornan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Autoimmune Hemolytic Anemia ◽  
Hazard Ratio ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Overall Mortality

Abstract Introduction Autoimmune hemolytic anemia (AIHA) is the most commonly reported autoimmune complication following hematopoietic stem cell transplantation (HSCT) with incidence of 2-6%. The risk factors and pathogenesis remain poorly understood. Treatment often requires multiple therapeutic agents with variable efficacy and outcome. However no study to date has shown whether AIHA directly results in increased mortality. In order to better understand the risk factors, mortality and management of post-HSCT AIHA, we carried out a retrospective analysis of 533 allogeneic HSCTs in adult patients performed at King's College Hospital between 2005-2011. Method The median follow-up period after HSCT was 31 months (range 2.9 – 100 months). The primary endpoint was the onset of AIHA, defined by positive direct agglutinin test (DAT) arising after the HSCT, with biochemical markers of hemolysis (raised serum lactate dehydrogenase (LDH), reduced haptoglobin, or spherocytes on the blood film). Hemolysis was considered significant if the drop in hemoglobin was more than 20 g/l. Cases of DAT positivity due to ABO antibodies, as well as those with history of AIHA or positive DAT prior to HSCT were excluded. Potential risk factors for development of AIHA were calculated with univariate followed by multivariate analysis comparisons of incidence of AIHA for each clinical stratum. Kaplan-Meier method was used to compare mortality caused by AIHA against overall mortality (OM), and transplant-related mortality (TRM). AIHA was modelled as a time-dependent variable when estimating mortality. All patients alive at last follow-up who did not develop AIHA were censored. Results We identified 19 cases of AIHA following HSCT (overall incidence 3.6%). The median time to onset from HSCT to AIHA was 202 days. AIHA was associated with HSCT from unrelated donors (p = 0.026; Hazard Ratio = 5.28, 95% CI = 1.22 – 22.9), and concordant sex between HSCT recipients and donors (p = 0.045; Hazard Ratio = 3.52; 95% CI = 1.03 – 12.1). No significant association was observed between AIHA and the following eight factors: recipient gender; primary hematological disease; source of hematopoietic stem cells; conditioning regimen (alemtuzumab/ATG versus non-alemtuzumab/ATG, and reduced intensity versus myeloablative); HLA mismatch between donor/recipient; ABO mismatch; recipient CMV status; and concurrent chronic GvHD. AIHA patients also exhibited high frequency of simultaneous alloimmunization to Rh antigens coinciding with the onset of AIHA, which was not due to difference in transfusion rates, and not observed in the population who tested negative for DAT. Majority of AIHA patients (14/19; 72%) required multiple agents for treatment, but only 9/19 (47%) cases achieved complete resolution of AIHA (1 with intravenous immunoglobulin; 2 with prednisolone alone; 6 with rituximab in combination with other agents). The median survival from onset of AIHA was 487 days (range 26 – 1977 days). We compared the mortality of the AIHA versus non-AIHA population that survived beyond the median time of onset for AIHA (202 days). Patients with post-transplant AIHA had a higher OM (p = 0.006, Hazard Ratio = 2.37, 95% CI = 1.28 – 4.39), 1-year OM of 22% versus 10% (p = 0.04) and 1-year TRM of 18% versus 4% (p = 0.001), respectively (Figure 1). 36% (4/11 cases) of deaths were attributable to AIHA. Conclusion The overall incidence of AIHA following allogeneic HSCT in our study was 3.6%. The risk factors associated with AIHA were receiving HSCT from unrelated donors, and matched gender between the donor/recipient, which has not been previously reported. We observed an association between allo and autoimmunization in the AIHA patients, suggesting a common immune defect underlying both phenomena. The most effective treatment was a combination regimen of rituximab with prednisolone or other immunosuppressive agents. The overall mortality rate for our AIHA patients was high at 53% (10/19 cases), with AIHA as a cause of death in 36% of deceased patients. We have shown that AIHA following HSCTs indeed leads to increased mortality with over 2 fold higher OM in the patients with AIHA. Figure 1 Figure 1. Disclosures McLornan: Novartis: Research Funding.

scholarly journals Risk Factors and Outcomes for Patients With Follicular Lymphoma Who Had Histologic Transformation After Response to First-Line Immunochemotherapy in the PRIMA Trial

2016 ◽  
Vol 34 (22) ◽  
pp. 2575-2582 ◽  
Author(s):  
Clémentine Sarkozy ◽  
Marek Trneny ◽  
Luc Xerri ◽  
Nick Wickham ◽  
Pierre Feugier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
International Prognostic Index

Purpose To study the outcome of histologic transformation (HT) in a large prospective cohort of patients with follicular lymphoma (FL) who previously responded to immunochemotherapy. Patients and Methods After a median 6-year follow-up of 1,018 randomly assigned patients from the PRIMA trial, disease progression was observed in 463 patients, 194 of whom had histologic documentation. Results Forty patients had histology consistent with HT, and 154 had untransformed FL (median time to recurrence, 9.6 v 22.8 months, respectively; P = .018). Thirty-seven percent of biopsies performed during the first year of follow-up showed HT corresponding to 58% of all HTs. Altered performance status, anemia, high lactate dehydrogenase level, “B” symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis were identified as HT risk factors. Response (complete v partial) to immunochemotherapy or rituximab maintenance had no impact on the risk of HT. After salvage treatment, patients with HT had less frequent complete response (50.3% v 67.4%; P = .03) and more disease progression (28.2% v 9.6%; P < .001) than patients without HT. Estimated overall survival for the patients with HT was poorer (median, 3.8 v 6.4 years; hazard ratio, 3.9; 95% CI, 2.2 to 6.9). Autologous stem cell transplantation improved the outcomes of patients with HT (median overall survival, not reached v 1.7 years) but not of patients with persistent FL histology. Conclusion HT in patients with FL who previously responded to immunochemotherapy is an early event associated with a poor outcome that may deserve intensive salvage with autologous stem cell transplantation. These data emphasize the necessity for biopsy at the first recurrence of FL.

Comparison of Lung Function after Nonmyeloablative Versus Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5105-5105
Author(s):  
Jason W. Chien ◽  
Michael B. Maris ◽  
Tanyalak Parimon ◽  
Brenda M. Sandmaier ◽  
David G. Maloney ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lung Function ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lung Function Decline ◽  
Hematopoietic Stem ◽  
Before And After ◽  
One Year

Abstract Lung function decline is a well-recognized occurrence after myeloablative hematopoietic stem cell transplantation (HCT) that has not been studied after nonmyeloablative conditioning regimens. We examined the lung function of patients before and after receiving nonmyeloablative and myeloablative preparative regimens. Before HCT, nonmyeloablative patients had lower baseline values of percent of predicted FEV1 (pFEV1) and FVC (pFVC), reflecting their greater ages and often, poorer, medical conditions. However, nonmyeloablative patients experienced a slower overall rate of pFEV1 decline after HCT (4% ± 17 versus 12.7% ± 32 per year, P = 0.001), with patients &gt;50 years of age having the lowest risk for rapid pFEV1 decline in a multivariable model. Rapid pFEV1 decline was associated with both total body irradiation (TBI) and non-TBI based myeloablative regimens. These findings were evident even one year or more after HCT. Myeloablative patients had a higher risk for death based upon pretransplant pFEV1 (HR 7.2 versus 3.9), with a 2-year survival rate of 0% among myeloablative patients with a pretransplant pFEV1 &lt;60% (30% among nonmyeloablative patients). These results suggested that despite having worse lung function, patients receiving the nonmyeloablative regimen might experience less pulmonary toxicity and had a lower risk of mortality associated with abnormal pretransplant lung function.

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