Impact of geriatric vulnerability on outcomes of older patients in allogeneic hematopoietic cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7017-7017
Author(s):  
Richard Jirui Lin ◽  
Theresa A Elko ◽  
Sean M. Devlin ◽  
Jessica Flynn ◽  
Ann Alice Jakubowski ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Older Patients ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Increased Risk

7017 Background: Older patients are at increased risk for complications and death following allogeneic hematopoietic cell transplantation (allo-HCT). Traditional transplant-specific prognostic indices such as hematopoietic cell transplant comorbidity index (HCT-CI) may not capture all underlying geriatric vulnerabilities, and in-depth evaluation by a geriatrician prior to transplant may not always be available. We hypothesize that routine pre-transplant assessments by interdisciplinary clinical providers may help uncover additional geriatric deficits. Methods: Using an institutional database of 457 adults age 60 years and older (range 60-78.7) who underwent first allo-HCT for hematological malignancies from 2010 to 2017, we retrospectively examined the prevalence and the prognostic impact of pre-transplant geriatric deficits identified by interdisciplinary clinical providers including geriatric domains of functional activity, cognition, medication, nutrition, mobility, and routine laboratory tests. Results: With a median follow-up of 37 months for survivors, the 3-year probability of overall survival (OS) was 50% (95% CI 45-55). The 2-year cumulative incidence of non-relapse mortality (NRM) was 25% (95% CI 22-28). Among pre-transplant geriatric variables, we found that impairment in instrumental activities of daily living (IADL) was associated with increased NRM and inferior PFS and OS. In multivariate analyses, mismatched donor, age-adjusted HCT-CI > 4 (aaHCTCI), and IADL impairment were associated with NRM, while high/very high disease risk index (DRI), IADL impairment, and positive CMV status were associated with OS. The combination of IADL impairment with either aaHCTCI or DRI readily stratifies NRM and OS, respectively. Conclusions: Our findings establish a simple assessment tool to risk stratify older patients prior to allo-HCT using IADL and aaHCTCI and DRI. These results may provide an entry point for prospective, interventional trials to reduce NRM and toxicities for older allo-HCT patients.

scholarly journals A Simple Geriatric Vulnerability Index for Older Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2176-2176 ◽  
Author(s):  
Richard J Lin ◽  
Theresa A Elko ◽  
Sean M Devlin ◽  
Ann A. Jakubowski ◽  
Armin Shahrokni ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Older Patients ◽  
Research Funding ◽  
Laboratory Tests ◽  
Hematopoietic Cell Transplantation ◽  
Ferritin Level ◽  
Vulnerability Index ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Prognostic Impact

Abstract Older patients are at increased risk for complications and death following allogeneic hematopoietic cell transplantation (allo-HCT). Traditional transplant-specific prognostic indices such as hematopoietic cell transplant comorbidity index (HCT-CI) may not capture all underlying geriatric vulnerabilities, and in-depth evaluation by a geriatrician prior to transplant may not always be available. We hypothesize that routine pre-transplant assessments by interdisciplinary clinical providers including advanced practice providers, nursing staff, physical therapists, occupational therapists, and dietitians, as well as common laboratory tests, may uncover additional geriatric deficits. Using an institutional database and the electronic medical records of 406 adults age 60 years and older (range 60-78.7) who underwent first allo-HCT for hematological malignancies from 2010 to 2016, we examined the prevalence and the prognostic impact of pre-transplant geriatric deficits identified by interdisciplinary clinical providers including geriatric domains of functional activity, cognition, medication, nutrition, and mobility (Table 1), and by routine laboratory tests. With a median follow-up of 39 months for survivors, the 3-year probability of overall survival (OS) and progression-free survival was 47% (95% CI 42-53) and 40% (95% CI 35-45), respectively. The 2-year cumulative incidence of non-relapse mortality (NRM) was 26% (95% CI 22-29). Among pre-transplant geriatric and laboratory variables, we found that impairment in instrumental activities of daily living (IADL) and pre-transplant ferritin level ≥1200 was independently associated with increased NRM and inferior OS. In the multivariate analysis, HCT-CI ≥3, IADL impairment, ferritin level ≥1200, and Karnofsky Performance Scale (KPS) <90 are predictive of NRM (Table 2). Similarly, IADL impairment, ferritin level ≥1200, and high/very high modified disease risk index predict OS (Table 2). Most importantly, the combination of either IADL impairment or ferritin ≥1200 with HCT-CI further stratifies NRM and OS into distinct risk categories, including a group of highly vulnerable, high risk patients with high HCT-CI (≥3) plus IADL impairment and/or ferritin level ≥1200 (Figure 1). Detailed examination of non-relapse death among all vulnerable patients (≥2 risk factors) reveals a higher proportion of death from organ toxicities than patients with zero or 1 risk factor. Our findings establish a rapid and simple assessment tool to risk stratify older patients prior to allo-HCT. While requiring validation, the geriatric vulnerability index can be easily completed and integrated into outpatient clinics and the electronic medical record. It may also provide an entry point for prospective, interventional trials aimed at reducing non-relapse mortality and toxicities, and at improving survival and quality of life of older allo-HCT patients. Disclosures Perales: Takeda: Other: Personal fees; Merck: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Abbvie: Other: Personal fees; Novartis: Other: Personal fees. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy.

scholarly journals Spontaneous fertility in a male thalassemic patient after allogeneic hematopoietic cell transplantation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Nicoletta Iacovidou ◽  
Maria Kollia ◽  
Emmeleia Nana ◽  
Theodora Boutsikou ◽  
Christos Savvidis ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Semen Analysis ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Thalassemic Patient ◽  
Increased Risk ◽  
Long Term Treatment

Patients with thalassemia major who received allogeneic hematopoietic cell transplantation are at increased risk of gonadal insufficiency and reduced fertility due to the toxicity of both the transfusional iron overload and the gonadotoxic effects of drugs used in the conditioning regimen. We present a case of an ex-thalassemic patient with spontaneous recovery of spermatogenesis that fathered a healthy, term male neonate. Maternal hemoglobin electrophoresis was within normal limits. At the age of 9.5 years the patient underwent hematopoietic cell transplantation. The conditioning therapy included busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg). No irradiation was administered. Thirty-two days after the hematopoietic cell transplantation the patient developed acute graft-versus-host disease needing long-term treatment with methylprednisolone, cyclosporine and immunoglobulin. Although consecutive semen analyses after the hematopoietic cell transplantation revealed azoospermia, the last semen analysis before conception, at the age of 33 years, was improved and normal follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (Te) levels were detected. The current pregnancy was the result of physical conception. In this case, it seems that thalassemia major along with the respective treatment prior to- and posthematopoietic cell transplantation did not irreparably impair spermatogenesis, probably due to the pre-pubertal time frame they were implemented. 对于接受异基因造血细胞移植的重型地中海贫血患者，由于输注性铁过载的毒性和预处理方案中所用药物性腺毒性作用这两方面的原因，都使其面临更大的性腺功能不全风险和更低的生育力。本文报道一例精子发生出现自然恢复的原重型地中海贫血患者，他成功孕育出一个健康的足月男婴。母体血红蛋白电泳在正常范围内。患者在9岁半时接受了造血细胞移植。预处理治疗包括白消安（16 mg/kg）和环磷酰胺（200 mg/kg）。未给予照射。造血细胞移植32天后，患者出现急性移植物抗宿主病，需要长期使用甲基强的松龙、环孢素和免疫球蛋白治疗。虽然造血细胞移植后连续的精液分析显示无精子症，但在33岁时受精前的最后一次精液分析有所改善，经检测发现卵泡刺激素（FSH）、黄体生成素（LH）和睾酮（Te）水平正常。目前的怀孕是自然受孕的结果。在这个病例中，看来重型地中海贫血以及造血细胞移植前后相应的治疗并没有对精子发生造成不可恢复的破坏，这可能是由于移植时处于青春发育期前时间段的原因。

Refined Disease Risk Index (DRI) and Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) Predict Survival after Haploidentical Stem Cell Transplantation: A Comparative Study with EBMT Risk Score in 220 Consecutive Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4400-4400 ◽  
Author(s):  
Maria Teresa Lupo-Stanghellini ◽  
Elisa Sala ◽  
Simona Piemontese ◽  
Mara Morelli ◽  
Raffaella Greco ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Stem Cell ◽  
Cell Transplantation ◽  
Risk Score ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Hematopoietic Cell ◽  
Comorbidity Index ◽  
Very High

Abstract Background Optimization of pre-transplant risk assessment is a crucial issue to improve the allo-HSCT decision making process. Actually 3 major algorithms are in use in clinical practice: the EBMT risk score, the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score and - more recently introduced - the refined Disease Risk Index (DRI). DRI was defined to calibrate HSCT outcome across studies and centers. It was developed as a tool to assign patients into risk groups based on disease type and status at the time of transplantation. The aim of the DRI is to provide a robust tool that can be used for prognostication, for the analysis and interpretation of retrospective data, whether conducted in single-center, multicenter, or registry settings, or within the context of the federally mandated center outcome reporting. The DRI can also be used for the stratification of patients entering prospective HCT clinical trials. DRI is not a fixed tool but instead it was conceived to be refined by the transplant community as new information becomes available. Here we are presenting the results of a retrospective study designed to evaluate the 3 aforementioned score in stratification and prognostication of transplant outcome after a haploidentical HSCT (haplo-HSCT). Patients and Methods We included 220 adult patients (pts - 138 male, 82 female) who underwent a haplo-HSCT for hematologic malignancies, between 2006 and 2014 and were reported to our Institutional database. Risk assessment score and outcome analysis included all consecutive pts receiving an haplo-HSCT as 1st allogeneic transplantation. Pts receiving haplo-HSCT as 2nd or 3rd HSCT were excluded from the present analysis. Median age was 49 years (range, 15-77). The cohort included a broad representation of diseases (138/220 acute leukemia, 30 Hodgkin lymphoma); 62 pts were in complete remission at transplant, 158 were presenting active disease. Conditioning regimens mostly rely upon the combination of treosulfan plus fludarabine (201/220) and total body irradiation (range 200 - 400 cGy) was utilized in 52 patients. GVHD prophylaxis consisted mostly of an mTor inhibitor (rapamycin) combined with mycophenolate mofetil. The majority of patients received peripheral blood stem cells from a family haploidentical donor as stem cell source, while only 4 patients received bone marrow transplant. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. Results The median follow-up for survivors was 37 months (r 6-107). The overall survival (OS) at 2-y was 35% and the transplant related mortality at 100-days 23%. The 2y OS according to EBMT / HCT-CI / DRI risk score are reported in table 1.a and figure 1. The evaluation of the HCT-CI impact after DRI stratification was able to show a significant difference in outcome showing better survival for pts with low DRI score and low HCT-CI score as expected (table 1.b). Discussion Refined DRI score and HCT-CI score predict survival after haplo-HSCT. The integrated application of refined DRI and HCT-CI may improve the definition of transplant eligibility for pts candidate to allogeneic HSCT form alternative donors including family haploidentical source. Table 1a. EBMT score 0-3 % pts 4-5 %pts > 5 %pts p 51% 17 34% 51 27% 32 0.07 HCT-CI score 0-2 3-4 >/= 5 48% 59 36% 31 0% 10 0.0001 DRI score Low-Intermediate High Very-High 61% 32 27% 51 5% 17 0.0001 Table 1b. HCT-CI 0-4 HCT-CI >/=5 p DRILow-Intermediate 64% 0% 0.0001 DRIHigh-Very High 29% 0% Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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