Frieder Keller Nephrology

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Frieder Keller Nephrology “Fall in Leukocyte Count for Monitoring of (1) Anti-Cancer, (2) Anti-Infective and (3) Immunosuppressive Drug Therapy“ Disclosures: NO Frieder Keller Nephrology

F Stegmeier Targeted Cancer Therapies in the Twenty-First Century: Lessons From Imatinib Clin Pharmacol Ther. 2010; 87: 543-552.

Effectivity and Toxicity

Effectivity and Toxicity

Gurney H How to calculate the dose of chemotherapy British Journal of Cancer (2002) 86, 1297 – 1302 CAF = cyclophosphamide, adriamycin/ doxorubicin, 5FU

Carus A. Impact of baseline and nadir neutrophil index in non-small cell lung cancer and ovarian cancer patients: Assessment of carbopoplatin chemotherapy for resolution of unfavourable neutrophilia J Translational Med. 2013, 11: 189 Survial benefit <= neutropenia < 1.0 x 10^9 /L <= neutrophils > 3.0 x 10^9 /L

Kohei Shitara Meta-analysis of leukopenia as a prognostic factor in patients with malignant disease undergoing chemotherapy Cancer Chemother Pharmacol. 2011; 68: 301–307

Mayer RJ; RECOURSE Study Group Mayer RJ; RECOURSE Study Group. Randomized trial of TAS-102 Trifluridine / Tipiracil for refractory metastatic colorectal cancer. N Engl J Med. 2015; 372: 1909-19.

Fall in Platelet count x 1000 / mm3 Sung C. A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients. PLoS Negl Trop Dis. 2016; 10: e0004851. Fall in Platelet count x 1000 / mm3 Rise in Hematocrit % „ … celgosivir activity in treating dengue fever based on hematological endpoints.”

Stevens DR, Sawinski D, Blumberg E, Galanakis N, Bloom RD, Trofe-Clark J. Increased risk of breakthrough infection among cytomegalovirus donor-positive/recipient-negative kidney transplant recipients receiving LD lower-dose valganciclovir prophylaxis. Transpl Infect Dis. 2015; 17: 163-73.

Fauci AS. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med. 1979; 301: 235-8.

Rasche FM. Cyclophosphamide pulse therapy in advanced progressive IgA nephropathy. Nephron Clin Pract. 2003; 93: c131-6. Kidney Dysfunction vs cell count nadir

Cyclophosphamie: Balance between efficacy and toxicity Survival without Death from vasculitis from infection

□ with CD19 B-cell suppression Sellier-Leclerc AL. Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood--follow-up after CD19 recovery. Nephrol Dial Transplant. 2012; 27: 1083-9. □ with CD19 B-cell suppression CD19 recovery Nephrotic syndrome YES NO Relaps

Mélet J. Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response. Arthritis Rheum. 2013; 65: 2783-90. T cell CD3+ CD4+ CD8+ Response = T cell depletion ARC Response NO ? YES

Moreso F. Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated with mycophenolate mofetil combined with low cyclosporine and steroid doses. Clin Transplant. 1998; 12: 198-205. „ … Patients receiving MMF showed a low incidence of biopsy proven rejection … ... All patients … who presented leukopenia recovered after MMF reduction dose … „

Conclusion: Titration Dose ! Titration curve Conclusion: Titration Dose ! Leukocyte count ← Dose NO YES Standard or high normal Dose Leukopenia Continue previous Dose Decrease Dose Candidates: … cyclophosphamide, adriamycin/ doxorubicin, cisplatin, carboplatin, trifluridine … celgosivir, valganciclovir … rituximab, mycophenolate … … azathioprine, lenalidomide …