Preparative Regimen Dosing for Hematopoietic Stem Cell Transplantation in Patients with Chronic Kidney Disease: Analysis of the Literature and Recommendations

AbstractHematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that has traditionally been associated with high treatment-related mortality due to direct regimen toxicity and a high incidence of graft-versus-host disease. Historically, pre-existing renal insufficiency has been considered an exclusion criterion for transplantation. The advent of nonmyeloablative conditioning regimens as a less toxic modality for treatment has made HSCT more accessible to elderly patients and patients with comorbidities, such as renal impairment. However, there is no clear standard for how to dose preparative regimens for patients with chronic renal impairment who undergo HSCT. This article serves as a review of the current literature to provide dosing recommendations for commonly used preparative agents in the setting of chronic kidney disease, with the aim of providing optimal dosing for this patient population

Increased Risk of Cervical Dysplasia in Long-Term Survivors of Allogeneic Stem Cell Transplantation—Implications for Screening and HPV Vaccination

AbstractAs more women survive allogeneic stem cell transplantation (SCT), the development of genital human papilloma virus (HPV)-related squamous intraepithelial lesions (SIL) warrants study. Thirty-five of 38 females followed prospectively long-term after SCT for hematological malignancies (median: 7 years posttransplant) were adults and had cervical cytology testing. Acute graft-versus-host-disease (aGVHD) occurred in 9 and chronic (cGVHD) in 34 patients. Six (17%) continued receiving systemic immunosuppressive therapy (IST) for cGVHD >3 years after SCT. Of 15 (43%) with abnormal cytology, 12 (34%) patients had HPV-related SIL (median time to SIL 51 months, range: 22-108) including high-grade SIL in 7 (20%). Patients requiring continued IST had the highest risk (odds ratio [OR] 4.6, 95% confidence interval [CI] 1.1-16.4; P = .019). This high incidence of SIL in long-term SCT survivors underscores the importance of gynecologic assessment after transplantation, especially in those requiring IST. This may portend an increased risk of genital or other HPV-related malignancies

Prolonged Chronic Graft-versus-Host Disease is a Risk Factor for Thyroid Failure in Long-Term Survivors After Matched Sibling Donor Stem Cell Transplantation for Hematologic Malignancies

AbstractWe studied thyroid function in 81 long-term survivors of allogeneic stem cell transplantation (allo-SCT), with a median follow-up of 84 months (range, 45 to 166 months). Median age at transplantation was 35 years (range, 6 to 66). Seventy-two of the patients received a total body irradiation (TBI)–containing conditioning regimen (n = 23, 12 Gy; n = 49, 13 Gy). Twenty-one of the patients (25.9%) had subclinical hypothyroidism, and 9 (11.1%) developed overt hypothyroidism at a median of 28 months (range, 3 to 78 months) after allo-SCT. Multivariate logistic regression analysis demonstrated that prolonged immunosuppressive therapy (IST) was significantly associated with subclinical hypothyroidism (odds ratio [OR] = 3.8) and overt hypothyroidism (OR = 2.6). Antithyroglobulin and thyroid peroxidase antibody were detected in 12 of 60 patients tested (20%). No correlation was found between the occurrence of thyroid antibodies and hypothyroidism (P = .13) or chronic graft-versus-host disease (cGVHD) (P = .55). In conclusion, thyroid dysfunction is relatively common after allo-SCT and is more likely to occur in patients receiving prolonged IST for cGVHD; however, thyroid dysfunction does not appear to be related to an antibody-mediated autoimmune process

Repair of Impaired Pulmonary Function Is Possible in Very-Long-Term Allogeneic Stem Cell Transplantation Survivors

AbstractBoth early- and late-onset noninfectious pulmonary injury are important contributors to the nonrelapse mortality seen after allogeneic stem cell transplantation (allo-SCT), particularly in subjects conditioned with high-dose total body irradiation (TBI). To characterize the kinetics of recovery from pulmonary injury in long-term survivors, we collected data on 138 subjects who survived > 3 years (median survival, 10.2 years) after predominantly TBI-based allo-SCT from their HLA-matched siblings. Baseline pulmonary function tests served as the reference for subsequent measurements at 3, 5, 10, and 15 years for each survivor. The only parameter showing a clinically and statistically significant decline post-transplant was adjusted diffusion capacity of lung for carbon monoxide (DLCO), which reached a nadir at 5 years but surprisingly normalized at the 10-year mark. Multivariable modeling identified chronic graft-versus-host disease (P < .02) and abnormal baseline-adjusted DLCO (P < .03) as the only significant factors associated with the decline in adjusted DLCO at 5 years but excluded smoking, conditioning intensity, baseline C-reactive protein level, TBI dose to the lungs, disease, and demographic variables. In conclusion, pulmonary injury as monitored by the adjusted DLCO continues to deteriorate in the first 5 years after allo-SCT but recovers at 10 years

Allogeneic haemopoietic transplantation for acute myeloid leukaemia in second complete remission: a registry report by the Acute Leukaemia Working Party of the EBMT

Allogeneic haemopoietic cell transplant (allo-HCT) may be curative in acute myeloid leukaemia (AML) in second complete remission (CR2) but the impact of reduced intensity (RIC) versus myeloablative conditioning (MAC) is uncertain. The Acute Leukaemia Working Party of the European Society for Blood and Bone Marrow Transplantation Registry studied an AML CR2 cohort characterised by age ≥ 18 years, first allo-HCT 2007–2016, available cytogenetic profile at diagnosis, donors who were matched family, volunteer unrelated with HLA antigen match 10/10 or 9/10 or haplo-identical. The 1879 eligible patients included 1010 (54%) MAC allo-HCT recipients. In patient

Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia

Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) (n = 8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR = 1.33 [95% CI = 1.21-1.48]; p <10(-5)), LFS (HR = 1.32 [95% CI = 1.19-1.45]; p <10(-5)) and GRFS (HR = 1.2 [95% CI = 1.1-1.31]; p <10(-4)) and higher NRM (HR = 1.37 [95% CI = 1.17-1.59]; p <10(-4)) and RI (HR = 1.27 [95% CI = 1.12-1.44]; p <10(-3)). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1.Peer reviewe

abo mismatching and haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia a report from the alwp of the ebmt

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