Long Term Psycho-Social Aspects and Risk Factors for Severe Infections, Ocular, Pulmonary, Bone, Thyroid and Other Complications after Allogeneic Hematopoietic Stem Cell Transplantation for Children with Hematologic Malignancies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3371-3371
Author(s):  
Christèle Ferry ◽  
Gladys Gemayel ◽  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Hélène Esperou ◽  
...  

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for children with hematologic malignancies. However, many long term complications are observed with a longer follow-up. Few data is available analyzing psycho-social aspects and risk factors of various long term complications in a same cohort of children. We have reviewed the charts of 112 children younger than 16 years, transplanted for hematologic malignancies between 1985 and 2000 at Saint Louis Hospital, and who survived at least 1 year after transplant. Landmark analysis and cumulative incidence using death and relapse as competing events were used to calculate incidences of complications after one year of HSCT. Univariate analysis used the Fine and Gray test and multivariate Cox model was used with chronic GVHD (cGVHD) as time dependent variable. Results: Median age at transplant was 8.3 years (0.73–15 years), median follow-up from 1 year after transplantation was 8 years (0.3–16.5). Most frequently, children had acute leukemia (n=101, 90%) and 92 patients were transplanted with an HLA-identical sibling donor.Total body irradiation (TBI) was used in 87 patients as part of conditioning regimen and fractionated TBI was used since march 1994 in 37 patients. At 10 years, overall survival was 75±5%, transplant related mortality (TRM) was 18%±4 and relapse 14±3%. Ten year cumulative incidence of severe infections (mostly bacterial) was 31%±4 (n=33); it was 44±4% for cataract (n=48); 20±4% for pulmonary dysfunction (mostly restrictive abnormalities) (n=20); 29±5% for osteoarticular complications (mostly osteonecrosis) (n=27); 36±4% for hypothyroidism (n=36); 11±3% for cardiac complications and 7±3% for secondary malignancies (n=8). The number of complications per patient increased with time, from 1 at a median observation time of 73 months to 3 at a median of 120 months. Factors related to patient, disease, donor and transplant characteristics were analyzed in univariate and multivariate analysis for complications with at least 20 events. There was a trend of higher risk of TRM (p=0.06), osteoarticular complications (p=0.09) and infections (p=0.07) for patients presenting cGVHD. cGVHD was significantly associated with higher risk of pulmonary dysfunction (p=0.02). However, single dose TBI (sTBI) or only TBI was the most important factor among other factors that increased the risk of cataract (p<0.001), pulmonary (p=0.004), osteoarticular (p=0.04) and thyroid complications (p<0.0001).Concerning psychological health and social issues; half of the patients had psychological disturbance, 13 patients had signs of depression, 16 history of eating behavior disorders. Half of the patients who had more than 18 years had an employment, 36 patients achieved normal scholarship, 69 had scholar difficulties and 12 patients achieved superior level studies. In conclusion with a longer follow-up in survivors of HSCT long term complications become an important issue. These complications reached no plateau even after 10 years. Development of less toxic conditioning regimen, avoid sTBI and probably better control of cGVHD may prevent late effects and improve quality of life of long term survivors.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2137-2137
Author(s):  
Satomi Ito ◽  
Maki Hagihara ◽  
Kenji Motohashi ◽  
Atsuo Maruta ◽  
Yoshiaki Ishigatsubo ◽  
...  

Abstract Background: Late pulmonary dysfunction is a clinical problem influencing on quality-of-life (QOL) in long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). In this study we retrospectively assessed pulmonary function test (PFT) in patients surviving 5 years or more after HSCT with intensified conditioning regimen and identified pre-and post-transplant risk factors. Methods: Sixty-five long-term survivors transplanted between May 1994 and March 2003 (minimum 5 years follow-up after HSCT) were included in this analysis. There were 36 males and 29 females. Median age was 39 years, with a range of 16 to 53 years. All patients were transplanted because of hematologic malignancies (20 patients with AML, 16 with ALL, 9 with MDS, and 20 with CML). The pre-transplant conditioning regimen consisted of thiotepa (200 mg/m2 for 2 days), cyclophosphamide (2,000–2,250 mg/m2 for 2 days), and total body irradiation (12.5 Gy in five fractions). The prophylaxis of graft-versus-host disease (GVHD) consisted of short-term methotrexate and cyclosporine or tacrolimus. Bone marrow (BM) from related donor or unrelated donor, and peripheral blood stem cell (PBSC) from related donor were transplanted in 33 patients, 22, and 10, respectively. PFT was performed pre-conditioning and then post-transplant at 3 months, 1 year, and thereafter annually. Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC ratio were used to measure ventilatory capacity. Vital capacity (VC) and total lung capacity (TLC) were used to measure lung volumes. Diffusion capacity for carbon monoxide (DLCO) was determined by using a carbon monoxide single-breath technique with correction for hemoglobin concentration. Results: Seven (11%) patients showed abnormalities in PFT after HSCT. Temporary abnormality (restrictive pattern) within 1 year was detected in 2 patients. Five patients developed late-onset and continuous abnormality (restrictive pattern in 2 patients, obstructive in 2, and mixed in 2) with a cumulative incidence of 8%. These were clinically diagnosed as having bronchiolitis obliterans in 3 patient and interstitial pneumonia in 1. DLCO was significantly lower after transplantation of PBSC than after BM (P=0.02 at 3 year and P=0.00 3 at 5 year). More than 40 years old, female, high risk of disease status, and abnormal PFT pre-transplant were related with a decline of PFT within 1 year after HSCT, but there were no association with PFT abnormality at 3 or 5 years. The cumulative incidence of late PFT abnormality in patients with CML was significantly higher than that in those with other than CML (P=0.01).Other factors including age, sex, smoking, disease status, and donor sources were not significant for developing late pulmonary dysfunction. Extensive chronic GVHD was associated with late PFT abnormality with statistical significance (P=0.002 for VC and P=0.01 for FEV1). Three of 7 patients receiving immunosuppressant at 5 years after HSCT had pulmonary complication. Conclusions: The results showed relatively a low incidence of PFT abnormality in long-term survivors who received HSCT with intensified conditioning regimen. However, late pulmonary dysfunction lowers QOL in survivors despite long-term remission of leukemia Longer follow-up should be needed to determine whether more patients with chronic GVHD will develop PFT abnormality.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5752-5752
Author(s):  
Kirill Kirgizov ◽  
Elena Skorobogatova ◽  
Denis Fedorenko ◽  
Elvira Volkova ◽  
Alexey Polushin ◽  
...  

Abstract Rationale. More than 70 000 of patients registered with multiple sclerosis (MS) registered in Russia annually. Some of adults and children with CNS autoimmune disorder (AD) require hematopoietic stem cell transplantation (HSCT). We analyzed long-term outcomes and late effects in adults and children with MS and neuromyelitis optica (NMO) after HSCT treated in three Russian centers. Patients and Methods. Sixteen children were treated in the Russian Children's Research Hospital in collaboration with Dmitry Rogachev Center: MS - 13, NMO - 3. MS: female (F) - 9, male (M)- 4; NMO: all females. MS median age - 16,8±1,6 y.o., median Expanded Disability Status Scale (EDSS) 6,16±0,2. NMO pts median age - 12,7±1,4 y.o. All patients had severe refractory disease. MS children received Cyclophosphomide and horse ATG, NMO - Treosulfan, Fludarabine, Rituximab and horse ATG. Nighty nine MS adults received HSCT in National Pirogov Medical Surgical Center with reduced-intensity BEAM-like conditioning regimen in mean age-35 y.o.; M:F=39:60; median EDSS = 3.5; disease status - 43 relapsing/remitting MS, 56 progressive MS. Thirty-two MS adult patients were transplanted in Raisa Gorbacheva Research Institute during 2 periods of time: 25 patients in 2000 - 2010 (mean age - 34,4 y.o., M:F=12:13, mean EDSS=4,3) with conditioning regimen BEAM and horse ATG and in 2018 (mean age - 36 y.o., M:F=3:4, mean EDSS=4.5) with conditioning regimen based on Cyclophosphomide and horse ATG. Results. Rapid improvement of EDSS registered in children - EDSS decreasing on 3,1±0,3 during first 60 days. Median follow-up - 52,1 ± 2,3 months (12-86 months). Two MS patients relapsed (clinical and MRI). Almost all NMO patients stopped the progression and improved neurologically (clinical and MRI) except 1 pt - died due to refractory ADV-infection. Median follow-up - 24,2±4,5 months (1- 62 months). MS patients late effects cardio-vascular - 5 pts, endocrine - 3 pts (all females). NMO patients late effects: cardio-vascular - 2 pts., late immune reconstitution - 1 pt. In Pirogov Medical Surgical Center group at 6 months post-transplant, neurological improvement or stabilization was observed in all the patients except one. Cumulative incidence of disease progression was 16.7 % at 8 years after HSCT. Sixty-four patients who did not progress during the first 3 years post-transplant and were monitored for more than 3 years were included in long-term outcome analysis. At the median long-term follow-up of 62 months, 47 % of patients improved by at least 0.5 points on the EDSS as compared to baseline and exhibited improvement during the entire period of follow-up; 45 % of patients were stable. In Raisa Gorbacheva Research Institute 50% of patients (group transplanted in 2000 - 2010) relapsed, group transplanted in 2018 - 4 patients were improved on therapy and 3 - stabilized. Conclusions. HSCT is used both for children and adults in Russia. It is successful approach for refractory MS and pediatric NMO treatment. In-time HSCT can significantly improve the outcome. Late effects can be found in these patients, so it's important to find it and give adequate rehabilitation. Thus, the risk/benefit ratio of HSCT in our population of these patients are very favorable. Disclosures No relevant conflicts of interest to declare.


Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 125-133 ◽  
Author(s):  
André Tichelli ◽  
Alicia Rovó ◽  
Alois Gratwohl

Abstract Non-malignant late effects after hematopoietic stem cell transplantation (HSCT) are heterogeneous in nature and intensity. The type and severity of the late complications depend on the type of transplantation and the conditioning regimen applied. Based on the most recent knowledge, we discuss three typical non-malignant complications in long-term survivors after HSCT, namely pulmonary, cardiovascular and renal complications. These complications illustrate perfectly the great diversity in respect of frequency, time of appearance, risk factors, and outcome. Respiratory tract complications are frequent, appear usually within the first two years, are closely related to chronic graft-versus-host disease (GVHD) and are often of poor prognosis. Cardiac and cardiovascular complications are mainly related to cardiotoxic chemotherapy and total body irradiation, and to the increase of cardiovascular risk factors. They appear very late after HSCT, with a low magnitude of risk during the first decade. However, their incidence might increase significantly with longer follow-up. The chronic kidney diseases are usually asymptomatic until end stage disease, occur within the first decade after HSCT, and are mainly related with the use of nephrotoxic drugs such as calcineurin inhibitors. We will discuss the practical screening recommendations that could assist practitioner in the follow-up of long-term survivors after HSCT.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4692-4692
Author(s):  
Jan Moritz Middeke ◽  
Regina Herbst ◽  
Stefani Barbara Parmentier ◽  
Gesine Bug ◽  
Mathias Hänel ◽  
...  

Abstract In patients with relapsed or refractory (r/r) Acute Myeloid Leukemia (AML), allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered to be the only treatment providing long-term disease control for fit patients. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy prior to HSCT in patients with r/r AML. Here, we report the long-term follow up of this Phase II, multi-center, Intent-To-Transplant study and the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range 40 - 75) were enrolled. Patients were scheduled for at least one cycle of salvage therapy with CLARA (clofarabine 30 mg/m2 and cytarabine 1 g/m2, days 1-5). Chemo-responsive patients with a donor received HSCT after first CLARA. In the event of a prolonged donor search, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine 30 mg/m2, day -6 to -3, and melphalan 140 mg/m2 on day -2. The ECOG score, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and Cumulative Illness Rating scale (CIRS) were obtained at study enrolment as well as prior to HSCT. Sixty-seven percent of the patients received HSCT within the trial. After a median follow up of 40months (95% CI, 38-49 months), the estimated 4-year OS (Figure 1) for all enrolled patients was 38% (95% CI, 28-50%) and Disease-Free Survival for transplanted patients was48% (95% CI, 36-64%). The CIR at four years was 30% (95% CI, 17-43%) and the NRM 22% (95% CI, 10-33%).Those patients who received an allogeneic HSCT within the trial had a median HCT-CI at the time of study enrollment of 1 (range, 0 - 6) compared to a median of 2 (range, 0 - 6) for those who did not proceed to allogeneic HSCT (p = .17). Corresponding figures for the CIRS were a median of 2 (range, 0 - 9) compared to 4 (range, 0 - 8) (p = .09). The median ECOG score was 1 (range, 0 - 3) in both groups. Compared to the time point of study enrollment, both the HCT-CI as well as the CIRS increased to a median of 2 (observed range of score, 0 - 7) and a median of 4 (observed range of score, 0 - 12), respectively, at the time of start of the conditioning regimen. This was almost exclusively due to an increase in infectious complications (Figure 2). Inmultivariate analysis, both the baseline HCT-CI and the ECOG score had a statistically significant impact with a HR of 1.22 (p = .025) and 1.72 (p = .001), respectively, on OS. Using a clofarabine-based salvage therapy combined with early allogeneic HSCT we were able to achieve good long-term results for patients with r/r AML. In this cohort, both the HCT-CI and the ECOG score gave prognostic information on OS, showing feasibility of comorbidity evaluation at the time of diagnose of r/r AML. Figure 1 OS of all enrolled patients Figure 1. OS of all enrolled patients Figure 2 Changes of the HCT-CI at baseline to HSCT Figure 2. Changes of the HCT-CI at baseline to HSCT Disclosures Middeke: Sanofi: Honoraria. Rösler:Janssen: Consultancy, Other: Travel/Accommodation/Expenses. Thiede:AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4438-4438
Author(s):  
Juan Xu ◽  
Tong Wu ◽  
Li Su ◽  
Bing Xin Ji ◽  
Wu Han Hui

Abstract Background Progressive multiple sclerosis (MS) is going with continuously disability and unresponsive to high dose steroid and immunomodulation. The autologous hematopoietic stem cell transplantation (ASCT) has been introduced in treatment of the forms of multiple sclerosis. Due to hematopoitic stem cell transplantation involved two processes that are conditioning with high dose immunosuppressive agents and stem cell transfusion. The short term outcomes (within 2 years after transplantation) do not preclude the immunosuppressant roles of conditionings, therefore the long term clinical outcomes after ASCT were evaluated for patients with progressive MS. Methods From Nov. 2001 to Jun. 2008, 34 patients with secondary progressive MS were treated with ASCT in our hospital. Of which, 26 patients were followed up more than 2 years till now. The median follow-up time was 40 months (3–83). There were 25 females (73.5%) and 9 males (26.5%). The median age of the patients was 36(20–51) years. Medium duration of disease was 36 months (15–156), and medium attacking interval time was 6.5 months (4–12). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. BEAM, Tiniposide(600 mg/m2), melphalan(140mg/ m2), carmustin (300 mg/m2)and cytosine arabinoside (800 mg/m2), were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale (EDSS). No maintenance treatment was administered if no disease progression. Results No deaths occurred following the treatment. All patients were observed into two groups, active-free group and activity group. The former include neurological improvement and neurological stabilization after transplantation. The latter include activity with progression and relapse without progression after improvement. Among 34 patients, 27 patients were in active-free group. Of twenty-one patients were with continuous neurological improvement without any active events. Median EDSS scores decreased from 6.0 (4.5–7.5) at transplantation to 2.0 (1.0–5) at last follow-up(p=0.000). Six patients remained neurological stable compared between the time of transplantation and last follow-up. There were 7 patients were in activity group. Of which, five patients had experience of neurological relapse during the follow-up period. However, the EDSS at relapse was lower than pre-transplantation, as well as the interval time between active events was longer than pre-transplantation. The low doses steroid relieved the symptoms in clinical. It seems to back to relapse and remission phase. There are two patients experienced neurological deterioration within 7 months after transplantation and need further immnosuppression treatment. The confirmed active-free survival rate was 79.14% and progression-free survival rate was 94.12% at 83 months according to Kaplan and Meier survival curve. Median remission-lasting time reached 63 months (95%CI 52–74). It was a significant difference compared with 7 months (95%CI 6–7) of pre-transplantation (P=0.000). We compared disease activity with attacking interval time, disease duration, patient’s age and EDSS of pre-transplantation. There is a relationship between active-free event and attacking interval time, OR=5.454, P=0.01(95% CI: 1.499 to 19.844,) and without relationship with duration of disease (OR=1.009, p=0.758), patient’s age (OR=1.136, P=0.147 and EDSS (OR=1.178, p=0.864) before transplantation. Conclusions ASCT with conditioning regimen of BEAM were able to improve or stabilize of neurological manifestations in most of progressive MS patients with failure of conventional therapy in long-term. The disease activitivy of post transplantation has a relationship with attacking interval time of pre-transplantation.


Author(s):  
Maria Otth ◽  
Sophie Yammine ◽  
Jakob Usemann ◽  
Philipp Latzin ◽  
Luzius Mader ◽  
...  

AbstractLongitudinal data on pulmonary function after pediatric allogeneic or autologous hematopoietic stem cell transplantation (HSCT) are rare. We examined pulmonary function and associated risk factors in 5-year childhood cancer survivors (CCSs) longitudinally. We included 74 CCSs diagnosed between 1976 and 2010, treated with HSCT, and with at least two pulmonary function tests performed during follow-up. Median follow-up was 9 years (range 6–13). We described pulmonary function as z-scores for lung volumes (forced vital capacity [FVC], residual volume [RV], total lung capacity [TLC]), flows (forced expiratory volume in 1 s [FEV1], maximal mid-expiratory flow [MMEF]), and diffusion capacity for carbon monoxide (DLCO) and assessed associations with potential risk factors using multivariable regression analysis. The median z-scores for FEV1, FVC, and TLC were below the expected throughout the follow-up period. This was not the case for RV, MMEF and DLCO. Female gender, radiotherapy to the chest, and relapse were associated with lower z-scores of FEV1, FVC, MMEF, RV or DLCO. Childhood cancer survivors after HSCT are at risk of pulmonary dysfunction. The complex and multifactorial etiology of pulmonary dysfunction emphasizes the need for longitudinal prospective studies to better characterize the course and causes of pulmonary function impairment in CCSs.


Author(s):  
Gizem Guner Ozenen ◽  
Serap Aksoylar ◽  
Damla Goksen ◽  
Salih Gozmen ◽  
Sukran Darcan ◽  
...  

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.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anar Gurbanov ◽  
Bora Gülhan ◽  
Barış Kuşkonmaz ◽  
Fatma Visal Okur ◽  
Duygu Uçkan Çetinkaya ◽  
...  

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.


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