Lost to Follow-up Rates Are Higher in Pediatric Than Adult Survivors, but Not By Transplant Type: A Report from the Center for International Blood and Marrow Transplant Research

Abstract Introduction Follow-up is an integral part of hematopoietic cell transplant (HCT) care which ensures accurate characterization of HCT-related outcomes as well as surveillance and intervention for complications. Despite the importance of follow-up of all HCT recipients at transplant centers, they may be lost to follow-up (LTFU). HCT recipients who are LTFU may be demographically or clinically distinct from HCT recipients who maintain regular center follow-up. Using population-based data from 17,550 adult and 4,279 pediatric HCT recipients from United States centers reported to the Center for International Blood and Marrow Transplant Research (CIBMTR), we characterize the incidence of, and predictors for, becoming LTFU. Methods The study included 2-year (yr) survivors of first allogeneic (10,367 adults and 3,865 children) or autologous (7,183 adults and 414 children) HCT for malignant and non-malignant disorders in the United States from 2002-2013 reported to the CIBMTR. LTFU was defined as a patient having missed 2 consecutive follow-up reporting periods. CIBMTR follow-up forms are collected annually for the first 6 yrs post-HCT and bi-annually thereafter. The cumulative incidence of LTFU HCT recipients was calculated. Marginal Cox models allowing adjustment for center effect were fit to evaluate risk factors for becoming LTFU among adults and pediatric allogeneic and autologous HCT survivors. Risk factors evaluated included: sociodemographic (age at HCT, sex, performance status, race, distance to center, income, health insurance, marital status) and disease/HCT-related (disease type, yr of HCT) factors. Results Among 2-yr allogeneic HCT survivors, the median age at the time of HCT was 49 yrs (range, 18-81) and 7 yrs (range, <1-18) for adult and pediatric recipients, respectively. Corresponding median follow-up was 75 months (mos) (range, 12-173) and 74 mos (range, 3-173). Health insurance coverage was public (23%) or private (64%) for adult recipients, and public (40%) or private (43%) for pediatric recipients. For 2-yr autologous HCT survivors, the median age at the time of HCT was 58 yrs (range, 18-82) and 4 yrs (range, <1-18) for the adult and pediatric recipients, respectively. Corresponding median follow-up was 76 mos (range, 3-174) and 73 mos (range, 6-173). Health insurance coverage was public (27%) or private (57%) for adult recipients, and public (48%) or private (39%) for pediatric recipients. The 10-year cumulative incidence of becoming LTFU among adult and pediatric allogeneic HCT recipients was 13% (95% CI, 12-14) and 25% (95% CI, 24-27), respectively. Among autologous HCT recipients, the 10-year cumulative incidence of becoming LTFU among adults and children was 15% (95% CI, 14-16) and 23% (95% CI, 19-28), respectively. (Figure 1) Among pediatric allogeneic HCT survivors, older age, non-white race, public or no insurance (referent: private), and earlier yr of HCT were significantly associated with increased LTFU risk. However, in adult allogeneic HCT survivors, younger age, non-malignant disease, public or no insurance (referent: private), living farther from the HCT center, and unmarried were significantly associated with higher risk of LTFU (Table 1). In pediatric autologous HCT survivors, males and Non-Hodgkin lymphoma (NHL)/Hodgkin lymphoma patients (referent: central nervous system tumors) were significantly associated with higher risk of becoming LTFU (Table 1), whereas for adult autologous HCT survivors, older age and multiple myeloma (referent: NHL) were significantly associated with decreased risk of LTFU. Conclusions The incidence of LTFU is significantly higher in pediatric than adult patients, with no difference between autologous and allogeneic HCT patients, regardless of age. We identified risk factors for LTFU that differed by age and HCT donor type. A national, comprehensive, risk-based approach to long-term follow-up focusing on minimizing the attrition in high-risk groups such as adolescent and young adult-aged HCT survivors and HCT survivors with non-private health insurance is needed. Future studies incorporating patient reported outcomes may help describe reasons for lack of long-term follow-up. Collection of accurate and meaningful epidemiologic and clinical data from all survivors can help develop and refine strategies to improve long-term outcomes of this population. Disclosures Parsons: Seattle Genetics: Research Funding.

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Predictors of Avascular Necrosis (AVN) of Bone after Long-Term Follow-Up of Allogeneic and Autologous Hematopoietic Cell Transplantation (HCT) for Malignant and Non-Malignant Disorders.

Blood ◽

10.1182/blood.v106.11.700.700 ◽

2005 ◽

Vol 106 (11) ◽

pp. 700-700

Author(s):

Liton Francisco ◽

Stephanie Campbell ◽

Andrea Carter ◽

Roberto Rodriguez ◽

Joseph Rosenthal ◽

...

Keyword(s):

Risk Factors ◽

Genetic Susceptibility ◽

Cumulative Incidence ◽

Systemic Steroids ◽

Allogeneic Hct ◽

Populations At Risk ◽

Increased Risk ◽

Autologous Hct

Abstract Patients undergoing allogeneic HCT are known to be at an increased risk of AVN. Chronic steroid use, to treat chronic graft vs. host disease (cGVHD) has been identified as a risk factor. Previous studies reporting AVN after allogeneic HCT are limited either due to small cohort size or reliance on registry data for passive reporting on outcomes such as AVN. Furthermore, little is known about the risk of AVN after autologous HCT. We report a retrospective chart review of 1595 consecutive patients undergoing HCT at City of Hope Cancer Center between 1976 and 1998, and surviving one or more years after HCT. The median age at HCT was 35 years (range, 0.6–71.5) and the median length of follow-up was 7.0 years (1–25.3). The cohort included 940 males (59%). In this cohort, 78 patients developed AVN of 163 joints, resulting in a mean of 2.1 affected joints per patient (range, 1 to 8). Diagnosis of AVN was confirmed by review of radiologic evidence of necrosis in the presence of clinical symptoms. The hip joint was the most common joint affected (70.5% of patients), followed by the knee (35%) and shoulder (26%). Symptoms developed a median of 38.7 months from HCT (12 to 199 months). The overall cumulative incidence was 6.2% at 15 years from HCT for the first reported AVN developing one or more years after HCT. Nineteen of 741 autologous HCT survivors developed AVN (cumulative incidence: 3.5% at 10 years), while 46 of the 746 allogeneic sibling donor HCT survivors (cumulative incidence, 6.2% at 10 years), and 12 of the 108 unrelated donor HCT recipients developed AVN (cumulative incidence 13.9% at 10 years, p<0.001). A multivariate analysis of the entire cohort identified exposure to cyclosporine, both for GVHD prophylaxis (relative risk (RR), 3.03, 95% confidence interval (CI), 1.4–6.5), and treatment of cGVHD (RR=4.1, 95% CI, 2.2–7.9), male sex (RR=2.1, 95% CI, 1.3–3.6), primary diagnosis of multiple myeloma (RR=7.5, 95% CI, 1.4–40.7) and Hodgkin disease (RR=10.8, 95% CI, 2.2–53.6) when compared with aplastic anemia to be independently associated with an increased risk of AVN after HCT. Among survivors of allogeneic HCT, presence of cGVHD (RR=4.2, 95% CI, 1.7–10.0), and treatment of cGVHD with a combination of systemic steroids, Cyclosporin, and Tacrolimus (RR=3.6, 95% CI, 1.7–7.7), compared to a combination of systemic steroids and Cyclosporin, were independently associated with an increased risk of AVN. Finally, no risk factors were identified for the development of AVN among autologous HCT recipients. AVN is a frequent and significantly debilitating consequence of HCT, frequently requiring surgical intervention, and potentially impacting the overall HRQL of the HCT survivors. This study describes the magnitude of risk in autologous and allogeneic HCT recipients and identifies cGVHD and use of immunosuppressive agents such as systemic steroids, Cyclosporin and Tacrolimus as risk factors, indicating the possible pathogenic role of Cyclosporin- and Tacrolimus-induced microangiopathy in the development of AVN in this population. Identification of genetic susceptibility and the role of interaction between therapeutic exposures and genetic susceptibility in handling these therapeutic exposures would further assist in identification of the populations at risk and the mechanistic pathways involved in the development of AVN in this population.

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Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

Scientific Reports ◽

10.1038/s41598-021-89216-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Robert Terziev ◽

Dimitri Psimaras ◽

Yannick Marie ◽

Loic Feuvret ◽

Giulia Berzero ◽

...

Keyword(s):

Risk Factors ◽

Cumulative Incidence ◽

High Grade Glioma ◽

High Grade ◽

Nucleotide Polymorphisms ◽

Increased Risk ◽

Radiation Induced ◽

Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

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Malignant Neoplasms in Long-Term Survivors of Bone Marrow Transplantation – Follow up

Blood ◽

10.1182/blood.v112.11.453.453 ◽

2008 ◽

Vol 112 (11) ◽

pp. 453-453 ◽

Cited By ~ 1

Author(s):

Bernhard Heilmeier ◽

Nadine Stowasser ◽

Gerard Socie ◽

Maria Teresa van Lint ◽

Andre Tichelli ◽

...

Keyword(s):

Risk Factors ◽

Graft Versus Host Disease ◽

Cumulative Incidence ◽

Marrow Transplantation ◽

Malignant Neoplasms ◽

Host Disease ◽

Graft Versus Host ◽

Long Term Survivors

Abstract Patients who receive allogeneic hematopoietic stem cell transplants have an increased risk for new malignancies because of several risk factors, including conditioning with radiation and chemotherapy, immune modulation, and malignant primary disease. The frequency of and risk factors for malignant neoplasm in long-term survivors should be assessed. A former analysis of the EBMT observing the 1036 patients of this study with a median observation time of 10.7 years showed older patient age and immunosuppressive treatment of chronic graft-versus-host disease as main risk factors for secondary malignancies. We have tried to determine the cumulative incidence and define potential risk factors for new malignancies in long-term survivors after marrow transplantation in a retrospective multi center follow-up study. This study of the Late Effects Working Party was performed with 45 transplantation centers cooperating in the European Cooperative Group for Blood and Marrow Transplantation. 1036 consecutive patients who underwent transplantation for leukemia, lymphoma, inborn diseases of the hematopoietic and immune systems, or severe aplastic anemia. Patients were transplanted before December 1985 and had survived more than 5 years. Reports on malignant neoplasms were evaluated, and the cumulative incidence was compared to that in the matched general population. Patient age and sex, primary disease and disease stage at transplantation, histocompatibility of the donor, conditioning regimen, type of prophylaxis of graft-versus-host disease, development of acute and chronic graft-versus-host disease, and treatment of chronic graft-versus-host disease were evaluated as variables. Univariate analysis was performed using the log rank test for the time until malignancy occurred; significant risk factors were studied in multivariate analysis (Cox regression). Median follow-up since transplantation was 17.9 years (range, 5 to 32.3 years). Malignant neoplasms were seen in 114 patients; the cumulative incidence was 4.0% at 10 years, 8.5% at 15 years, 14.0% at 20 years and 21.0% at 25 years. The rate of new malignant disease was 6-fold higher than that in an age-matched control population (P <0.001). The most frequent malignant diseases were neoplasms of the skin (23 patients), breast (16 patients), thyroid gland (13 patients), oral cavity (12 patients), uterus including cervix (7 patients), and glial tissue (3 patients). Median ages of patients and their donors at the time of transplantation were 21 years for both groups (range 0.5 – 52 years). Follow up data were avaible in 636 patients, 100 patients were deceased at the time of prior analysis, 300 patients were lost to follow up. Compared with the analysis of the same cohort of patients 10 years ago, the most striking increase in secondary malignancies was seen in breast cancer (4-fold), thyroid cancer (3-fold) and neoplasms of the skin and oral cavity (2-fold). In multivariate analysis patient age above 30 years (hazard ratio 1.8, 95% CI 1.2 – 2.6; p=0.006), radiotherapy for conditioning (hr 2.3, CI 1.2 – 4.3; p=0.01) and immunosuppression (hr 1.5, CI 1.0 – 2.2; p=0.05) (in particular cyclosporine or methotrexate) were risk factors for new malignancies after hematopoietic stem cell transplantation. In conclusion longer followup shows the continuous increase of the cumulative incidence of secondary neoplasms in long-term survivors. With longer follow-up a shift in the risk factors occurs: Until 10–15 years after allogeneic transplantation immunosuppression is the major risk factor for new malignancies, whereas more than 15 years after transplantation radiotherapy becomes the dominant risk factor.

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Long-term Risk of Advanced Neoplasia After Colonic Low-grade Dysplasia in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz114 ◽

2019 ◽

Vol 13 (12) ◽

pp. 1485-1491 ◽

Cited By ~ 8

Author(s):

Michiel E De Jong ◽

Sanne B Van Tilburg ◽

Loes H C Nissen ◽

Wietske Kievit ◽

Iris D Nagtegaal ◽

...

Keyword(s):

Risk Factors ◽

Cumulative Incidence ◽

Low Grade ◽

Advanced Neoplasia ◽

Inflammatory Bowel ◽

Independent Risk Factors ◽

Male Sex ◽

Low Grade Dysplasia

AbstractBackground and AimsThe long-term risk of high-grade dysplasia [HGD] and colorectal cancer [CRC] following low-grade dysplasia [LGD] in inflammatory bowel disease [IBD] patients is relatively unknown. We aimed to determine the long-term cumulative incidence of advanced neoplasia [HGD and/or CRC], and to identify risk factors for advanced neoplasia in a nationwide IBD cohort with a history of LGD.MethodsThis is a nationwide cohort study using data from the Dutch National Pathology Registry [PALGA] to identify all IBD patients with LGD between 1991 and 2010 in the Netherlands. Follow-up data were collected until January 2016. We determined the cumulative incidence of advanced neoplasia and identified risk factors via multivariable Cox regression analysis.ResultsWe identified 4284 patients with colonic LGD with a median follow-up of 6.4 years after initial LGD diagnosis. The cumulative incidence of subsequent advanced neoplasia was 3.6, 8.5, 14.4 and 21.7%, after 1, 5, 10 and 15 years, respectively. The median time to develop advanced neoplasia after LGD was 3.6 years. Older age [≥ 55 years] at moment of LGD (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.44–2.06), male sex [HR 1.33, 95% CI 1.10–1.60], and follow-up at an academic [vs non-academic] medical centre [HR 1.37, 95% CI 1.07–1.76] were independent risk factors for advanced neoplasia following LGD.ConclusionsIn a large nationwide cohort with long-term follow-up of IBD patients with LGD, the cumulative incidence of advanced neoplasia was 21.7% after 15 years. Older age at LGD [≥55 years], male sex and follow-up by a tertiary IBD referral centre were independent risk factors for advanced neoplasia development after initial LGD.

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Encoraging Results after Alternative Donor Transplantation for Myelodysplastic Syndrome.

Blood ◽

10.1182/blood.v112.11.1964.1964 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1964-1964

Author(s):

Franco Locatelli ◽

Adrienne Moreno-Madureira ◽

Pierre Teira ◽

Mary Eapen ◽

Mei-Jie Zhang ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Cumulative Incidence ◽

Chronic Gvhd ◽

Marrow Transplant ◽

Hematopoietic Stem ◽

Monosomy 7 ◽

Neutrophil Recovery ◽

Blood And Marrow Transplant

Abstract Hematopoietic stem cell transplantation (HSCT) remains the treatment of choice for children with myelodysplastic syndromes (MDS). Umbilical cord blood (UCB) represents an alternative source of hematopoietic stem cells for transplantation in children without a HLA-matched sibling. We examined risk factors influencing outcomes after UCB transplantation (UCBT) in 70 children (40 males and 30 females; median age 7 years, range 0.8–18) with MDS reported to the European Working Group of MDS in Childhood, the Center for International Blood and Marrow Transplant Research or the Eurocord-European Blood and Marrow Transplant Group. Excluded were patients who had received prior autologous/allogeneic HSCT and those with Down syndrome, Fanconi anemia, or MDS that evolved to AML prior to HSCT. Patients had refractory cytopenia (RC, n=31), refractory anemia with excess blasts (RAEB, n=30), and RAEB in transformation (RAEB-t, n=9). All patients received a single UCB unit and myeloablative preparatory regimen. Karyotype analysis (available for 68 of 70 patients) was normal in 22 patients, while the remaining 46 had cytogenetic abnormalities, the most frequent being monosomy 7 (n= 23). In all pairs but one, donor-recipient histocompatibility was determined by serology (low-resolution typing) for HLA-A and -B and allele-level typing for DRB1. UCB units were HLA matched (A, B, DRB1) in 4 cases, 1-locus, 2-loci and 3-loci mismatched in 34, 26 and 5 cases, respectively. The day-60 probability of neutrophil recovery was 76%; in multivariate analysis, transplantation of HLA matched or 1-locus mismatched UCB, irradiation-containing preparatory regimen, cell dose ≥ 6x107/kg (pre-cryopreservation) and monosomy 7 were associated with faster neutrophil recovery. The 100-day probability of grade II-IV acute graft-versus-host disease (GVHD) was 30% (95% CI, 20–41). The 3-year cumulative incidence of chronic GVHD was 23% (95%CI 14–33). Five of 16 patients with chronic GVHD had limited and 11 extensive chronic GVHD. Twenty-nine patients died from transplantation-related complications, the 3-year cumulative incidence of transplantation-related mortality (TRM) was 41% (95% CI 29–52). Three deaths were related to GVHD. In multivariate analysis, TRM was lower when transplants were performed after 2001 (HR 0.41, 95%CI 0.20–0.84, p=0.015). Thirteen patients had recurrent disease and 11 were dead at last follow up. No variable predicted disease recurrence. With a medium follow-up of 39 months (range 10 – 105), the 3-year probability of disease-free survival (DFS) for the entire cohort was 39%; it was 50% when transplantation was performed after 2001 compared to 27% in the earlier period (p=0.02). After 2001, patients received UCB containing higher cell doses and the interval from diagnosis to transplantation was shorter. The 3-year DFS was 61% for the 23 patients with monosomy 7 compared to 30% for patients with other karyotypes (p=0.042). In multivariate analysis, year of transplantation (prior to 2001) and cytogenetic abnormalities other than monosomy 7 were independent risk factors predicting treatment failure, HR 2.38, (95% CI: 1.14–5.0, p=0.02) and HR 2.04,(95% CI: 1.11–3.70, p=0.02), respectively. The 3-year DFS was not influenced by MDS variant. Given the relatively small sample size the influence of MDS variant on transplant-outcome requires validation in a larger series. These data indicate that UCBT is an acceptable alternative in children with MDS without a HLA-matched related or unrelated adult bone marrow donor. The results of UCBT have improved in recent years and monosomy 7 does not confer an unfavourable outcome.

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Hematopoietic Stem Cell Transplantation As a Successful Salvage Strategy for Relapsed Acute Promyelocytic Leukemia (APL): A Mayo Clinic Series

Blood ◽

10.1182/blood.v124.21.3995.3995 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3995-3995

Author(s):

Gita Thanarajasingam ◽

James M. Foran ◽

Vivek Roy ◽

Lisa Sproat ◽

William J. Hogan ◽

...

Keyword(s):

Induction Therapy ◽

Mayo Clinic ◽

Disease Status ◽

Patient Characteristics ◽

Single Institution ◽

Hematopoietic Stem ◽

Allogeneic Hct ◽

Autologous Hct

Abstract Background: Relapse after ATRA-based induction therapy is relatively uncommon in patients with acute promyelocytic leukemia (APL). Long term follow up studies have estimated a 15-25% relapse rate. Autologous and allogeneic hematopoietic stem cell transplantation (HCT) has been used as an effective salvage strategy. We present a single institution study of the outcomes of patients with relapsed APL that underwent HCT. Methods: After due IRB approval, the Mayo Clinic Transplant Database was retrospectively reviewed to identify all patients across three Mayo Clinic sites with relapsed APL that underwent HCT from 1995-2013. Data was abstracted at diagnosis and at relapse. The aims of this study were to report the descriptive characteristics of patients, with a focus on HCT outcomes. Results: Baseline Patient Characteristics A total of 15 patients (9 (60%) males) with relapsed APL that underwent HCT were identified. Median age was 36 years (range: 19-63) and median follow up from diagnosis was 8.8 years (range: 1.7-17). 2 (13%) deaths (1 from relapse) were recorded. 14 (93%) received ATRA and anthracycline-based induction therapy and 1 received anthracycline-based induction without ATRA. All relapsed patients achieved a complete remission (CR) after induction. Median time to relapse was 1.6 years (range: 0.6-3.9). 10 (67%) patients had a medullary relapse (hematologic-7(70%), cytogenetic -2 (20%) and molecular-1(10%)), 3 (20%) had additional extramedullary (EM) disease (CNS-2, myeloid sarcoma-1), while 2 (13%) presented with EM disease only (CNS-2). Salvage regimens included ATRA in 5 (33%) patients and arsenic trioxide (ATO) in 8 (53%) patients. 12 (80%) patients were transplanted in CR2 and 1 in CR3 (7%), while 2 (13%) had persistent disease (PD) at time of HCT. Allogeneic HCT 4 (27%) patients with a median age of 37 years (range: 33-49) underwent allogeneic HCT. 2 (50%) patients received myeloablative (MA) conditioning and 2 received reduced-intensity conditioning (RIC). 2 patients who underwent MA HCT had PD at time of transplant, while 1 patient in CR3 received a RIC. 2 (50%) patients developed acute GVHD while 2 (50%) had extensive stage chronic GVHD. At a median follow up of 2.6 years (range: 0.3-10.9), 3 (75%) patients remain alive and disease-free. 1 patient died of infectious complications within 100 days of transplant. Autologous Transplantation 11 (73%) patients with a median age of 40 years (range: 23-68) underwent autologous HCT with MA conditioning. 7 (64%) patients were in molecular remission at time of HCT, 3 (27%) patients transplanted before 2004 were in cytogenetic remission and information about type of remission was unavailable in 1 patient. At a median follow up of 6.8 years (range: 0.5-16) since HCT, 1 (9%) patient had a documented relapse at 175 days after HCT and died of disease-related complications. 10 (91%) are alive and in remission. Conclusions: Our single-institution study reaffirms the efficacy of HCT for APL patients with medullary and EM relapse. Autologous HCT has excellent long-term results in selected patients in CR2. Allogeneic HCT was mainly reserved for patients with high risk disease (CR3) and persistent disease at time of HCT. Table 1: Baseline Patient Characteristics N (%) Number of patients 15 Follow up (years) (median, range) 8.8 (1.7-17) Age at diagnosis (years) (median, range) 36 (19-53) Gender Male 9 (60%) Female 6 (40%) Sanz risk score High 4 (29%) Intermediate 8 (57%) Low 2 (14%) Induction Regimen ATRA + anthracycline 14 (93%) Anthracycline-based 1 (7%) Response to induction therapy CR 15 (100%) Time from diagnosis to relapse (years) (median, range) 1.6 (0.6 - 3.9) Type of relapse Hematologic 7 (47%) Cytogenetic 2 (13%) Molecular 1 (7%) Hematologic and EM 3 (20%) CNS only 2 (13%) Salvage regimen ATRA-based 5 (33%) ATO-based 8 (53%) Chemotherapy only 2 (13%) Table 2: Outcomes at HCT N (%) Age at HCT (years) (median, range) 38 (23-68) Disease status at HCT CR2 12 (80%) CR3 1 (7%) PD 2 (13%) Type of HCT Allogeneic 4 (27%) Autologous 11 (73%) Conditioning regimen Myeloablative 13 (87%) Non-myeloablative 2 (13%) Follow up since HCT (years) (median, range) 4.5 (0.3 - 16.3) Disease status at last follow up CR 13 (86%) Relapsed disease 1 (7%) Unable to assess 1 (7%) Alive at last follow up 13 (87%) Disclosures No relevant conflicts of interest to declare.

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Health-Related Quality of Life (HRQL) in Adult Long-Term Hematopoietic Cell Transplant (HCT) Survivors: A Report from the Bone Marrow Transplant Survivor Study.

Blood ◽

10.1182/blood.v104.11.2254.2254 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2254-2254

Author(s):

Smita Bhatia ◽

Liton Francisco ◽

Andrea Carter ◽

K. S. Baker ◽

Stephen J. Forman ◽

...

Keyword(s):

Quality Of Life ◽

Risk Factors ◽

Health Insurance ◽

Relative Risk ◽

Return To Work ◽

Household Income ◽

P Value ◽

Allogeneic Hct

Abstract We describe HRQL reported by adult survivors of autologous and allogeneic HCT and the risk factors associated with poor HRQL. Eligible subjects were individuals undergoing HCT at either City of Hope or the University of Minnesota between 1974 and 1998, and surviving two or more years after HCT. We analyzed the data from 1003 HCT survivors older than 21 years enrolled in a retrospective cohort study who had completed a validated City of Hope HCT-QOL tool. Of these, 54.5% were males, 80.2% were Caucasians, and 55% had received allogeneic HCT. The primary diagnoses included CML (n=233), AML (n=241), NHL (n=200), ALL (n=99), HD (n=88), and other (n=142). The median age at HCT was 35.4, median age at study participation: 43.4 years, and the median length of follow-up: 9.4 (2 to 28 years). Survivors’ responses were compared with those of the population norms in Physical, Psychological, Social and Spiritual domains, and overall quality of life (QOL). Poor QOL was defined as QOL scores less than two standard deviations below that reported for the tool norms. Using this definition, 9.2% of this cohort was identified to have poor overall QOL; 13.7% with poor Physical; 10% with poor Psychological; 6.7% with poor Social; and 4.3% with poor Spiritual well-being. Table below shows the results of the risk factors identified for poor QOL by multivariate analysis. Age, sex, type of HCT, and time since HCT were not associated with poor QOL. Thus, overall 9% of the long-term HCT survivors report poor overall QOL. Certain vulnerable sub-populations exist, specifically, low household income, difficulty in obtaining health insurance, inability to return to work, and the presence of pain and anxiety that impact upon the HRQL of this population, and require additional attention and possible intervention. Predictors of Poor Risk Factors for Poor QOL Overall QOL Physical Psychological Social Spiritual Relative Risk (p-value) Relative Risk (p-value) Relative Risk (p-value) Relative Risk (p-value) Relative Risk (p-value) Non-white race 2.1 (0.06) 2.4 (0.005) 1.6 (0.1) 2.0 (0.06) 0.5 (0.2) Inability to return to work 3.4 (0.003) 4.9 (<0.001) 3.6 (<0.001) 3.6 (0.002) 0.8 (0.7) Inability to return to school 2.4 (0.2) 4.6 (0.005) 5.2 (0.002) 1.1 (0.8) 0.9 (0.9) Difficulty in obtaining health insurance 1.7 (0.1) 1.9 (0.04) 0.9 (0.9) 3.6 (<0.001) 2.2 (0.05) Absence of health insurance 2.6 (0.05) 1.3 (0.6) 0.7 (0.5) 1.6 (0.4) 4.2 (0.005) Household income <$20k 3.0 (0.04) 0.9 (0.9) 4.4 (0.006) 2.2 (0.1) 3.1 (0.05) CGVHD 2.1 (0.02) 1.8 (0.02) 1.9 (0.04) 1.4 (0.3) 1.5 (0.3) Severe pain 8.8 (<0.001) 12.6 (<0.001) 2.4 (0.07) 5.4 (0.001) 2.8 (0.07) Severe anxiety 240.2 (<0.001) 5.3 (0.001) 60.2 (<0.001) 7.8 (<0.001) 19.7 (<0.001)

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Delayed Chronic Kidney Disease (CKD) after Hematopoietic Cell Transplantation (HCT).

Blood ◽

10.1182/blood.v108.11.552.552 ◽

2006 ◽

Vol 108 (11) ◽

pp. 552-552

Author(s):

Andrea R. Carter ◽

Michael Choi ◽

Can-Lan Sun ◽

Liton Francisco ◽

Stephen J. Forman ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Unrelated Donor ◽

Transplant Recipients ◽

Increased Risk ◽

Autologous Hct ◽

One Year

Abstract Exposure to pre-transplant nephrotoxic agents, total body irradiation (TBI), and presence of chronic graft-versus-host disease (cGVHD) have been identified as risk factors for developing CKD after HCT. However, small sample size, short follow-up post-HCT, and varying definitions of CKD have precluded a precise estimation of the magnitude of risk and associated risk factors. The aim of the current study was to describe the incidence and risk factors associated with the development of delayed CKD in HCT survivors. Eligible subjects underwent HCT for hematological malignancies or severe aplastic anemia at City of Hope, survived at least one year post-transplant, and were free of CKD at one year post-HCT. Information on pre-transplant therapeutic exposures and post-transplant CKD was obtained via medical record abstraction. All CKD cases were defined according to the National Kidney Foundation’s definition based on glomerular filtration rate (GFR) values. The endogenous filtration marker creatinine was used to estimate GFR values. CKD was defined as a sustained elevation of serum creatinine which infer a GFR of less than 60 mL/min/1.73 m2 for 3 months or longer. The equation used to calculate GFR was as follows: GFR = 186 x (Pcr) −1.154 x (age) − 0.203 (x 0.742 if female) (x 1.210 if African American). Totally, 1,546 eligible subjects were identified (median age at HCT of 34.4, median length of follow-up 6.2 years; autologous HCT in 718 patients [46%], related donor HCT in 726 patients [47%], and unrelated donor HCT in 102 patients [7%]; 59% of subjects (n=913) were male). A total of 65 patients were identified with CKD, resulting in a cumulative incidence of 3.6% [95% confidence interval (CI), 2.6% to 4.6%] at five years post–HCT and 4.8% at 10 years (autologous HCT: 2.9% at five years; matched sibling HCT: 4.1%; matched unrelated donor HCT: 10.5%, p<0.05). In allogeneic transplant recipients, older age at HCT (RR per increase of five years, 1.34; 95% CI, 1.30 to 1.38), prophylaxis/treatment of GvHD with cyclosporine and/or tacrolimus (RR, 4.32; 95% CI, 1.25 to 14.89), and a primary diagnosis of Multiple Myeloma (RR=5.38, 95% CI=1.79 to 16.15) were associated with increased risk. For autologous transplant recipients, older age at HCT was associated with increased risk (RR per increase of five years, 1.33; 95% CI, 1.29 to 1.38). Of note, use of TBI, and chemotherapeutic agents for conditioning, and a history of fungal infection were not associated with risk of delayed CKD development. This study describes the magnitude of risk of delayed chronic kidney disease in a large cohort of long-term survivors of autologous and allogeneic HCT, as well as identifies high risk groups in this population, thus setting the stage for appropriate long-term follow-up of the vulnerable sub–groups. Incidence of Chronic Kidney Disease in 1+ Year Survivors of HCT Incidence of Chronic Kidney Disease in 1+ Year Survivors of HCT Incidence of Chronic Kidney Disease in 1+ Year Survivors of HCT (by Type of Transplant) Incidence of Chronic Kidney Disease in 1+ Year Survivors of HCT (by Type of Transplant)

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Cardiovascular Risk Factors in Hematopoietic Cell Transplantation (HCT) Survivors: Role in Development of Subsequent Cardiovascular Disease

Blood ◽

10.1182/blood.v118.21.330.330 ◽

2011 ◽

Vol 118 (21) ◽

pp. 330-330

Author(s):

Saro H. Armenian ◽

Can-Lan Sun ◽

Tabitha Shannon ◽

Emily Blum ◽

Liton Francisco ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Cumulative Incidence ◽

Chronic Gvhd ◽

Allogeneic Hct ◽

Increased Risk ◽

History Of

Abstract Abstract 330 Introduction: Advances in transplantation strategies and supportive care have resulted in a growing number of long-term HCT survivors. In the general U.S. population, cardiovascular disease is a leading cause of morbidity and mortality, and cardiovascular risk factors (CVRFs), including diabetes hypertension and dyslipidemia are well-established modifiers of the risk. There is increasing evidence that HCT survivors may be at risk for CVRFs that can potentially result in an increased risk of cardiovascular morbidity. However, there is a paucity of knowledge regarding the magnitude of risk and associated risk factors for CVRFs after HCT, and the role these CVRFs play in the subsequent development of cardiovascular disease such as stroke, myocardial infarction, and congestive heart failure, in long-term survivors of HCT. Methods: A retrospective cohort study design was used to describe the cumulative incidence of CVRFs and cardiovascular disease in 1+year survivors of HCT, taking into consideration the competing risk of death. Cox proportional hazards regression analysis was used to calculate relative risk (RR) estimates and 95% confidence intervals (CI), adjusted for relevant covariates. Definition of CVRFs was per the National Cholesterol Education Program Adult Treatment Panel III criteria. Survivors taking immunosuppressant medication for management of graft vs. host disease (GvHD) at the time of CVRF diagnosis were excluded from the regression analysis. Cardiovascular disease was defined per the American College of Cardiology established case definitions. Results: 2041 consecutive one-year survivors who underwent HCT for hematologic malignancies between 1995 and 2004 at City of Hope were included in the analysis. Median age at HCT was 44.1 years (0.6–78.9); 57.6% were female; 62.5% were non-Hispanic white and 24.5% were Hispanic; 41% underwent allogeneic HCT; 26.5% of allogeneic HCT survivors had a history of chronic GvHD; 49.9% received total body irradiation (TBI). Cardiovascular risk factors: After 12,551 person-years of follow-up, the 10-year cumulative incidence of diabetes, hypertension, and dyslipidemia was 16.8%, 36.1% and 43.5%, respectively; 10-year cumulative incidence for multiple (2+) CVRFs was 29.5%. The cumulative incidence of CVRFs was significantly higher for allogeneic HCT recipients (Table). Multivariate analysis adjusted for gender, race/ethnicity, diagnosis, and conditioning-related exposures, revealed older age at HCT and obesity to be risk factors for all three CVRFs. Allogeneic HCT survivors with a history of chronic GvHD were at highest risk for diabetes (RR=32.4, 95% CI: 16.6–63.2, p<0.01), hypertension (RR=12.0, 95% CI: 5.5–26.1, p<0.01), and dyslipidemia (RR=7.2, 95% CI: 4.2–12.3, p<0.01) when compared to autologous HCT recipients. Cardiovascular disease occurred in 117 individuals, at a median 3.8 years following HCT (range 0.1–13.9). The 10-year cumulative incidence of cardiovascular disease was 7.4%, and was highest among survivors with multiple CVRFs (10.9% vs. 5.9% in those with <2 CVRFs, p=0.02). Furthermore, survivors with multiple CVRFs were at 1.8-fold risk (95% CI: 1.1–3.3, p=0.04) of subsequently developing cardiovascular disease when compared to survivors with <2 CVRFs. Conclusions: Allogeneic HCT survivors are at a substantially increased risk for CVRFs following HCT, and chronic GvHD and/or its treatment are critical modifiers of this risk. Survivors with multiple CVRFs are at highest risk for development of cardiovascular disease following HCT. These findings provide rationale for close monitoring and aggressive interventions for this high-risk population in order to reduce cardiovascular morbidity and mortality. Disclosures: No relevant conflicts of interest to declare.

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