Haploidentical Stem Cell Transplantation for Adolescent With Drug Resistant Acute Lymphoblastic Leukemia Case report Anton Klodzinskiy JSC «Republican Research Center for Emergency Care» (Astana)

5-year overall survival10-year overall survival Children with ALL aged years 87.5%83.8% Children with ALL aged years 61.4%60.4% Young adults with ALL aged years 44.8%30.8%

Patient with T Cell ALL without CR in age subgroups Pui Ch-H. et al. Hematology Am Soc Hematol Educ Program. 2004: Hematology Am Soc Hematol Educ Program. CR - complete remission

Outcome for 27 patients grafted from haploidentical donors in remission and in refractory state Klingebiel TKlingebiel T et al. Blood Rev Sep;18(3):181-92Blood Rev. pSUR - probability of survival

Patient Сh., 18 y.o. male Diagnosed with T cell ALL (T-II) in Sept 2012 Leukocyte count: 41 х 10 9 /L Cytogenetics: 46, ХY [11] Mediastinal lymphadenopathy - 1,7х0,8х0,6 cm Splenomegaly +3 cm below costal margin

Chemotherapy Blasts in BM 50% 25% 60% No CR Blasts in BM 50% 25% 60% No CR RALL-2005 PRED 60 mg/m 2 Dexa 10 mg/m days DNR 45 mg/m 2 8, 15,22, 29 days VCR 2 mg 8, 15,22, 29 days Dexa 10 mg/m days DNR 45 mg/m 2 8, 15,22, 29 days VCR 2 mg 8, 15,22, 29 days 1-7 days Ara-C 75 mg/m 2 4 х 4 days CPH 650 mg/m 2 36, 50, 64 days 6-MP 60 mg/m days Ara-C 75 mg/m 2 4 х 4 days CPH 650 mg/m 2 36, 50, 64 days 6-MP 60 mg/m days 8-36 days38-64 days ProphaseInduction IInduction II Blasts in BM 45% 80% No CR Blasts in BM 45% 80% No CR ALL-REZ BFM 2002 Dexa 20 mg/m days VCR 2 mg 1, 6 days Mtx 1 g/m 2 /36 h 1 day Dexa 20 mg/m days VCR 2 mg 1, 6 days Mtx 1 g/m 2 /36 h 1 day 1-6 дни Dexa 20 mg/m days VCR 2 mg 1 day Ara-C 2х3 g/m days Dexa 20 mg/m days VCR 2 mg 1 day Ara-C 2х3 g/m days 1-5 дни Блок F1Блок F2 FLAG Fludarabine 30 mg/m2/d iv over 30 min d1-5 Cytarabine (Ara-C) 2 g/m2/d iv over 3 hrs, 2 hrs after fludarabine, d1-5 Filgrastim 5 mcg/kg/d sc to begin day 6 until neutrophil recovery Fludarabine 30 mg/m2/d iv over 30 min d1-5 Cytarabine (Ara-C) 2 g/m2/d iv over 3 hrs, 2 hrs after fludarabine, d1-5 Filgrastim 5 mcg/kg/d sc to begin day 6 until neutrophil recovery 1-5days 53% marrow blasts on day 21 after FLAG; 67% blasts in peripheral blood, WBC 15х10 9/ L; Diameter of neck lymph nodes > 4 cm No CR 53% marrow blasts on day 21 after FLAG; 67% blasts in peripheral blood, WBC 15х10 9/ L; Diameter of neck lymph nodes > 4 cm No CR

Day +13 Engraftment (+ Engraftment syndrome) Day + 14 complete remission Day+24 acute GvHD stage IV (skin grade +; gut grade ++++) Today is Day +160 complete remission, but… Weight loss (5540 kg); Diarrhea ml/day; Protein 30 g/L 1 st lineMethylprednisolone 2 mg/kg + Tx, MMF, budesonide p.o. 2 nd lineInfliximab 5 mg/kg 2; Infliximab 10 mg/kg 2 3 d lineMesenchymal Stem Cell 1х10 6 /kg 2

Iskakova A. Kemaikin V. Kolesnev A. Nemirovchenko A. Olifirovich A. Pivovarova I. Satayeva M. Tleugalieva E. Tusipova A. Vildanova R. Cheishvili M