Pharmacologic Basis for High‐Dose Chemotherapy

Doroshow, James H.; Synold, Timothy W.

doi:10.1002/9780470987070.ch12

Cited by 5 publications

(6 citation statements)

References 327 publications

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“…Fludarabine, a strongly immunosuppressive purine analogue was selected to replace cyclophosphamide. Cyclophosphamide, long known to have dose limiting cardiac toxicity and risk of hemorrhagic cystitis is increasingly recognized as contributing to the morbidity and mortality of traditional regimens through hepatic toxicity (11, 12). …”

Section: Introductionmentioning

confidence: 99%

Outcomes following HSCT Using Fludarabine, Busulfan, and Thymoglobulin: A Matched Comparison to Allogeneic Transplants Conditioned with Busulfan and Cyclophosphamide

Bredeson¹,

Zhang²,

Agovi³

et al. 2008

Biology of Blood and Marrow Transplantation

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We have reported a lower incidence of acute graft versus host disease (aGVHD) with a novel conditioning regimen using low dose rabbit anti-thymocyte globulin (TG, Thymoglobulin) with fludarabine and intravenous busulfan (FluBuTG). To assess further this single center experience, we performed a retrospective matched pair analysis comparing outcomes of adult patients transplanted using the FluBuTG conditioning regimen with matched controls from patients reported to the CIBMTR receiving a first allogeneic hematopoietic stem cell transplant (HCT) after standard oral busulfan and cyclophosphamide (BuCy). 120 cases and 215 matched controls were available for comparison. Patients receiving FluBuTG had significantly less treatment related mortality (12% vs 34%, p<0.001) and grades II–IV aGVHD (15% vs 34% p<0.001) compared to BuCy patients. The risk of relapse was higher in the FluBuTG patients (42% vs 20%, p<0.001). The risks of chronic GVHD (cGVHD) and disease free survival (DFS) were similar in the cases and controls. These results suggest that the novel regimen FluBuTG decreases the risk of aGVHD and transplant mortality after HLA-identical sibling HCT, but is associated with an increased risk of relapse, resulting in similar DFS. Whether these conditioning regimens may be more suitable for specific patient populations based on relapse risk requires testing in prospective randomized trials.

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Section: Introductionmentioning

confidence: 99%

Outcomes following HSCT Using Fludarabine, Busulfan, and Thymoglobulin: A Matched Comparison to Allogeneic Transplants Conditioned with Busulfan and Cyclophosphamide

Bredeson¹,

Zhang²,

Agovi³

et al. 2008

Biology of Blood and Marrow Transplantation

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“…The kidneys were not shielded during TBI. Allogeneic graft recipients received prophylaxis against acute GVHD with immunosuppressive drugs, usually cyclosporine or tacrolimus plus methotrexate or mycophenolate mofetil 9 . Prophylaxis for infections included acyclovir to prevent herpes simplex virus and varicella zoster infection, trimethoprim/ sulfamethoxazole to prevent Pneumocystic jivecii infection, oral fluconazole or itraconazole for prophylaxis of fungal infection, and pre-emptive ganciclovir for cytomegalovirus disease among viremic patients 10 - 14 .…”

Section: Methodsmentioning

confidence: 99%

Markers of coagulation activation and acute kidney injury in patients after hematopoietic cell transplantation

Hingorani

Seidel

Pao

et al. 2015

Bone Marrow Transplant

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Acute kidney injury (AKI) is common after hematopoietic cell transplant (HCT). The etiology of AKI is unknown because biopsies are rarely performed. The pathophysiology of injury is inferred from clinical data. Thrombotic microangiopathy (TMA) is often invoked as the cause of renal injury. Patients > 2 years undergoing their first HCT at Fred Hutchinson Cancer Research Center (FHCRC) participated in this study. We prospectively measured plasma markers of coagulation activation, (PAI-1 and tPA) and fibrinolyis (D-dimer) weekly in 149 patients during the first 100 days post-transplant. Cox proportional hazards modeling was used to determine associations between these markers and AKI (doubling of baseline serum creatinine). Kruskal-Wallis test was used to determine associations between day 100 urinary albumin to creatinine ratios (ACR) and these markers. Thirty one percent of patients developed AKI. Though elevations in these markers occurred frequently, neither PAI-1 nor tPA were associated with development of AKI. D-dimer was associated with a slightly increased risk of AKI (RR=1.76; p-value 0.04). None of these markers were associated with micro- or macroalbuminuria at day 100. The lack of an association with AKI suggests that endothelial injury in the form of TMA is not a common cause of AKI early after transplant.

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“…The kidneys are not shielded during TBI. Recipients of allogeneic grafts received prophylaxis against acute graft-versus-host disease (GVHD) with cyclosporin or tacrolimus plus methotrexate, sirolimus, or mycophenolate mofetil (12). These immunosuppressive agents are tapered off around day 80 if there is no evidence of GVHD.…”

Section: Technique Of Hctmentioning

confidence: 99%

Estimating GFR in Adult Patients with Hematopoietic Cell Transplant

Hingorani

Pao

Schoch

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Formal evaluation of kidney function before and after hematopoietic cell transplant is important to determine conditioning regimens, type of transplant, and medication dosing. Serum creatinine and estimating equations may not accurately assess kidney function.Design, study, participants, & measurements Existing estimating equations for GFR were compared with an iohexol measure of GFR in a prospective cohort study of 50 patients undergoing hematopoietic cell transplant and subsequent care at the Fred Hutchinson Cancer Research Institute from 2009 to 2013. Patients underwent iohexol GFR, serum creatinine, and cystatin C determination at baseline and day 100 posthematopoietic cell transplant. Iohexol GFR measurements were compared with the CKD Epidemiology Collaboration, Inker CKD Epidemiology Collaboration cystatin C with and without serum creatinine, Modification of Diet in Renal Disease, and Cockcroft-Gault estimating equations using Bland-Altman analysis and McNemar's test. The iohexol measurements were also compared with blood samples collected simultaneously on filter paper.Results Mean differences between iohexol GFR and eGFR on the basis of Bland-Altman analyses ranged from 220.6 to +15.4 ml/min per 1.73 m 2 at baseline and 212.7 to +12.9 ml/min per 1.73 m 2 at day 100. The CKD Epidemiology Collaboration and Modification of Diet in Renal Disease estimating equations classified 64% of patients with a GFR,90 at baseline compared with 38% by iohexol GFR (P=0.003 and P,0.01, respectively). No statistically significant differences were seen at day 100. The filter paper GFR had a mean difference of 0 at baseline and 5.9 at day 100. Additionally, 21%-37% and 57%-89% of eGFRs were within 10% and 30%, respectively, of the iohexol GFR at baseline, and 16%-34% and 72%-84% were within 10% and 30%, respectively, of the iohexol GFR at day 100; 98% of the filter paper estimates at baseline were within 30%, and 46% were within 10% of iohexol GFR.Conclusions The estimating equations are neither accurate nor precise in the hematopoietic cell transplant population, and clinical decision may require measurement of GFR.

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Pharmacologic Basis for High‐Dose Chemotherapy

Cited by 5 publications

References 327 publications

Outcomes following HSCT Using Fludarabine, Busulfan, and Thymoglobulin: A Matched Comparison to Allogeneic Transplants Conditioned with Busulfan and Cyclophosphamide

Outcomes following HSCT Using Fludarabine, Busulfan, and Thymoglobulin: A Matched Comparison to Allogeneic Transplants Conditioned with Busulfan and Cyclophosphamide

Markers of coagulation activation and acute kidney injury in patients after hematopoietic cell transplantation

Estimating GFR in Adult Patients with Hematopoietic Cell Transplant

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