Hiperleukositosis: Kedaruratan Onkologi

Kegawatan OnkologiKegawatan karena penyakitnya:Kompresi corda spinalisHyperleukositosisSindroma Vena Cava SuperiorAPML (Acute Promielositik Lekemia)Kegawatan oleh karena terapi:Sindroma tumor lisisTyphlitisDemam dan neutropenia

Insidensi9-13% = ALL5-22% = AML100% = CML fase kronikLebih sering= ALL neonatus, AML, Tcell ALL dengan mediastinal mass, hypodiploid ALL.

HiperleukositosisWBC > 100,000Hiperviskositas pada LMAGangguan metabolik lebih sering pada LLA

Penyebab KematianPerdarahan SSP/ ThrombosisLeukostasis PulmonalGangguan metabolik

PatogenesisHiperviskositas -> Tekanan Vena sentral naikViskositas darah naikAgregrasi leukositPembentukan trombusMyeloblasts-> lebih besar, menaikkan viskositas

Patogenesis

Leukosit tinggi-> agregrasi di vaskular serebralMerusak pumbuluh darahPerdarahan

PatogenesisHiperviskositas -> Tekanan Vena sentral naikViskositas darah naikAgregrasi leukositPembentukan trombusMyeloblasts-> lebih besar, menaikkan viskositas

Gejala HiperviskositasSistem syaraf pusat:

AsimtomatikPerubahan status mentalNyeri kepalaPandangan kaburKejang, komaGejala strokPapilledemaDistensi arteri atau vena retina.AL >100,000 evaluasi dan tanda hiperleukositosis

Gejala HiperviskositasParu-paru:

DyspnoeaHipoksiaAsidosisSianosis

Pemeriksaan LaboratoriumElektrolit SerumAsam UratTes Fungsi ginjalProfil KoagulasiRo Dada

Terapi HiperleukositosisHidrasi iv 3 lt/BSA/hari. Alkalinisasi dengansodium-bicarbonateAllopurinolAT

Transfusi tukar mengurangi 52-66%Kemoterapi harus dilakukan segeraIrraadiasi SSP 400cGy untuk mencegah perdarahan -- kontroversi

Terapi Hiperleukositosis

Sindroma Tumor LisisKemoterapi pecahnya selKadang spontan, awal terapi, khususnya Burkitts LymphomaTrias Metabolik:HyperuricemiaHyperkalemiaHyperphosphatemia (dihubungkan dengan hypocalcemia)Dihubungkan dengan besarnya tumor burden, rapid doubling time, sensitifitas terhadap kemoterapi

Sindroma tumor lisisHyperuricemia akibat degradasi purine dari sel tumorGejala:10-15 mg/dl: lethargy, mual, muntah, kristal urat dalam urin, kolik renal, hematuria>20 mg/dl: potensi untuk gagal ginjal, perubahan status mental

Sindroma Tumor LisisTerapi HiperurisemiaMenurunkan produksi allopurinol, RasburicaseMelarutkan alkalinization (goal urine pH 7.0-7.5)Mengurangi konsentrasi Hiperhidrasi

Oksidasi nucleotide precursors menjadi asam uratNucleotidePrecursorsHypoxanthineXanthineUric AcidAllantoinxanthineoxidaseUrateUrateOxidasexanthineoxidasepH~7.3pH~5.6XXX = tempat aksi allopurinol= tempat aksi rasburicase

Sindroma Tumor LisisHyperkalemia -- pengeluaran K dari sel tumor yang matiGagal ginjal, acidosis, transfusi PRC tambah burukTerapi standar (insulin/glucose, bicarb, kayexalate, dll)

Sindroma Tumor LisisHyperphosphatemia/hypocalcemiaLimfoblast memiliki 4x lebih banyak PO4 daripada limfosit normalFiltrasi glomerolus untuk mengeliminasi PO4Hati-hati pembentukan dan presipitasikristal calcium phosphate apabila Ca x PO4 > 60 mg/dl

Konsekuensi Sindroma Tumor LisisHiperkalemiaLemah, disritmiaHiperfosfatemia:Hipokalsemia, gagal ginjalHipokalsemia:Tetani, Perubahan status mental, kejangHiperurisemia:Nefropati asam urat, oliguri, gagal ginjal

Tatalaksana Monitoring:Kreatinin serum, nitrogen urea darahSodium, Potasium, Kalsium, fosfatKadar LDH dan asam uratEKGMonitoring jantung sampai terapi selesaiHiperhidrasi iv 24-48 jam sebelum kemoterapi

Pencegahan Sindroma Tumor LisisHidrasi:2-3 lt/m2/hari untuk meningkatkan ekskresi asam urat dan fosfatGoal: BJ urin: < 1.010Alkalinisasi: NaHCO3 iv tidak direkomendasikan lagi

PencegahanMenurunkan produksi asam urat:Allupurinol menghambat xanthine oxidase300mg/m2/hari dibagi 3 dosis po/ivMengurangi risiko gagal ginjal24-48 jam sebelum kemoterapiMengkonversi asam urat menjadi bentuk yang lebih larut dalam air (allantoin) denganRasburicase

Recombinant Urat OxidaseRaburicase lebih efektif dari pada allupurinol0,1-0,2 mg/kgBB/hari infus 30 menit, 1-7 hari

DialisisIndikasi:OliguriaHiperkalemiaAzotemiaHiperfosfatemiaHiperurisemia refrakterHemodialisis lebih efektif

KonklusiSuspek klinis apabila AL > 100.000/ mikroliterPengukuran segeraAntileukemia seawal mungkin

*The risk of hyperviscosity is greater with AML than with ALL (myeloid cells are stickier than lymphoid cells), but the risk of tumor lysis syndrome is greater with ALL than with AML. These are TENDENCIES, though. One can see symptomatic hyperviscosity with ALL, and AML patients have tumor lysis syndrome.*Increased pulm markings diffusely on CXRAny of the above findings in the context of a white blood cell count >100,000 must be treated as evidence of hyperviscosity caused by hyperleukocytosis, but DO NOT FORGET a differential diagnosis. Patients can present with pneumonia, congestive heart failure, renal infiltration with leukemia or lymphoma cells, infection, intoxication, or other etiologies for each of the signs listed above, and these alternatives need to be considered*Increased pulm markings diffusely on CXRAny of the above findings in the context of a white blood cell count >100,000 must be treated as evidence of hyperviscosity caused by hyperleukocytosis, but DO NOT FORGET a differential diagnosis. Patients can present with pneumonia, congestive heart failure, renal infiltration with leukemia or lymphoma cells, infection, intoxication, or other etiologies for each of the signs listed above, and these alternatives need to be considered*The choice between exchange transfusion and leukapheresis depends in part on patient size and in part on physician preference. Contact surgery IMMEDIATELY upon learning of a patient with an elevated white blood cell count and any of the above signs of hyperviscosityEncourage the surgeon to place the largest caliber central line possible, to facilitate leukapheresis Very small children and infants may not tolerate the fluid shifts associated with leukapheresis and will require exchange transfusion insteadNo study has demonstrated a benefit, in terms of long term outcome, for leukapheresis or exchange transfusionThe decreased white blood cell count in the peripheral blood is temporary, and reverses within hoursDropping the peripheral white blood cell count does NOT alter the risk of tumor lysis syndrome. Therefore, the role of leukapheresis and exchange transfusion is in the management of symptomatic hyperviscosity. In the absence of symptoms, these interventions are not necessary.The vast majority of the tumor cells are present in the bone marrow, even in patients with peripheral white blood cell counts exceeding 500,000*Allopurinol blocks the production of uric acid by inhibiting xanthine oxidaseRasburicase is recombinant urate oxidase and catalyzes the conversion of uric acid to allantoin. This drug works almost instantaneously to reduce uric acid levels to almost undetectable.