IM R3 박미나 Case conference
마 0 희 (F/34) ADM C.C: easy bruising P.I: 2002 년 1 월 AML M2 진단 후 AI induction, AI consolidation #1-2 시행 후 complete remission 되었으나 그 후 f/u loss 되었던 환자 년 7 월 AML relapse 발견되어 AI induction, AI consolidation#1 후 2005 년 2 월 allogenic BMT(donor: 언니 ) 시행함. 그 후 외래에서 cyclosporin 복용하며 f/u 해오던 중 최근 easy bruising 있으며 일반 혈액 검사에서 혈소판 감소 양상 심화되어 자세한 검사 위해 입원 PMHx: DM/HTN/Tbc/hepatitis(-/+/-/-) op Hx (-) FHx: none, PHx: alcohol(-) smoking(-)
Review of system weight loss(-), fever sense(-), chill(-), fatigue(+) sweating(-) rash(-), itching(-), multiple petechia (+) headache(-), gum bleeding(-), sore throat(-) cough(-), sputum(-), hemoptysis(-) chest pain(-), palpitation(-), edema(-), dyspnea(-) A/N/V/D/C(+/-/-/-/-), jaundice(-), melena(-) frequency(-), dysuria(-), hematuria(-) dizziness(+), tremor(-), syncope(-)
Physical examination 120/ 회 /min-20 회 /min-36.3°C Alert mentality, chronic ill appearence Multiple petechia on both extremity and ant.chest wall Pale conjunctiva, clear sclera No neck vein engorgement, no cervical LN enlargement CBS without crackle, RHB without murmur soft and flat abdomen, no hepatosplenomegaly no abdominal T/RT, normoactive bowel sound No pph pitting edema, no CVA tenderness
Laboratory finding CBC/DC 1420/mm g/dl –17.1 % -7K/mm 3 (seg: 54%, lympho 42%, mono 2%) (MCV fl, MCH 36.4pg) Chemistry T/D bil 0.5/0.0mg/dL AST/ALT 41/42 U/L T-prot/Alb 6.1/3.9g/dL ALP/rGT 183/38 U/L BUN/Cr 5/0.6mg/dL Na/K/Cl 139/3.6/103 mEq/L Glucose 115mg/dL LD/CK 551/51U/L Ca /Mg /P /uric acid 8.6/2.7/3.1/3.9 mg/dL Cyclo ng/mL( )
Chest X-ray
Old chart review BM: AML M2 (blast 42%) FISH : AML1/ETO (+), Chromosome: t(8:21)(q22:q22.2) BM: Treated AML (blast 1.2%) FISH : AML1/ETO (+), Chromosome: No cytogenic abNL BM: AML remission (blast 0.5%) FISH : AML1/ETO (+), Chromosome: No cytogenic abNL AI induction Ara-C (D1-7)+ Idarubicin (D1-3) AI consolidation#1 Ara-C (D1-5)+ Idarubicin (D1-3) ID Ara-C (D1-5)
04.3. BM: AML M2 relapse (blast 38%) FISH : AML1/ETO (+), Chromosome: t(8:21)(q22:q22.2) BM: AML M2 remission (blast 1.4%) FISH : AML1/ETO (+), Chromosome: t(8:21)(q22:q22.2) BM: Treated AML remission FISH : AML1/ETO (-), Chromosome: No cytogenic abNL AI induction Ara-C (D1-7)+ Idarubicin (D1-3) AI consolidation#1 Ara-C (D1-5)+ Idarubicin (D1-3)
BM: Engraft of tri-lineage cells(post BMT 39 days) FISH : AML1/ETO (-), Chromosome: no cytogenic abNL mixed chimerism (1.6% 미만 ) Cyclosporin 200/100mg, 100mg, 100/50mg po ( ng/Ml) 복용하며 OPD F/U Allogenic bone marrow transplantation
날짜 WBC(mm 3 )Hgb(g/dl)PLT(mm 3 )Dfferential count 3/ KSeg82.4% 4/ KSeg65.3% 5/ KSeg63.8% 6/ KSeg67% 7/ KSeg60.7% BM: Post BMT state in remission FISH : AML1/ETO (-), Chromosome: no cytogenic abNL complete chimerism (0.8%)
날짜 WBC(mm 3 )Hgb(g/dl)PLT(mm 3 )Dfferential count 3/ KSeg82.4% 4/ KSeg65.3% 5/ KSeg63.8% 6/ KSeg67% 7/ KSeg60.7% 8/ KSeg44%, Lymph 48% 9/ KSeg34%, Lymph 62% 9/ KSeg40%, Lymph 51%
Bone marrow exam ( )
Bone marrow exam ( ) Blast : 23.6%, cellularity : 70% => Post BMT state of acute myelogenous leukemia (FAB M2) in relapse Chromosome study with BM: 46XX,t(8:21),(q22:q22) /46,XX FISH:AML/ETO rearrangement-> positive (15.1%)
날짜 WBC(mm 3 )Hgb(g/dl)PLT(mm 3 )Dfferential count 9/ KSeg51%, Lymph 44% 9/ KSeg61.2%, Lymph 27.2% 10/ KSeg43%, Lymph 52% 10/ KSeg20%, Lymph 78% 10/ KSeg16%, Lymph 77% 10/ KSeg16%, Lymph 79% 10/ KSeg25%, Lymph 70%
AML M2 in relaspe (s/p allogenic BMT) AI induction Donor lymphocyte infusion
Review < Treatment of AML in relapse after hematopoietic cell transplantation>
Therapy of newly diagnosed AML Induction therapy Cytarabine+anthracycline CR No CR Consolidation#1 Cytarabine+anthracycline Consolidation#1 Cytarabine+anthracycline High dose Ara-C Consolidation#2 Cytarabine+anthracycline High dose Ara-CAuto PBSCT Consolidation#1 Cytarabine+anthracycline Allo BMT Induction therapy Cytarabine+anthracycline Good Px group Intermediate, poor Px group
Induction therapy 60-70% => complete remission Without futher therapy: almost relapse Induction + consolidation therapy Prevent relapse, prolong survival 30% pts long term survival Rarely cure with standard chemotherapy Allogenic SCT : rescue 20% of relapsed pts with AML Poor outcome (early relapse) => new agents
10-36% of pts in acute leukemia ~70% in advanced disease, reveiving T-depleted grafts Selection of pts, timing of transplantation, type of conditioning regimen Median survival : 3-4 months if no futher Tx
Immunosuppressive agents stop Reinduction chemotherapy Second HCT DLI (Donor lymphocyte infusion) Cessation of immunosuppressive agents (cyclosporin) immunomodulator agents (IFN- , IL-2) Conventional or hIgh dose chemotherapy : 30-40% remission, but short duration, most relapse and die
Long term disease free survival in selected pts 2yr survival: 2-25%, long term survival: 10-35% Tx related mortality 25-50%, relapse rate: 40-65% Poor outcome short interval (HCT~relapse (1yr)) GVHD after 1 st transplant, older age, poor performance status, no remission at 2 nd allograft Only responding reinduction (usually 2 nd transplant GVHD prophylaxis ↓ to maximize GVL effect Reduce intensity conditioning FLAG (fludarabine+high dose Ara-C, GCSF) : median duration of 2 nd CR 14months
Discontinuation of immunosuppression -> reinfusion, activation of cytotoxic T lymphocytes of donor GVL effect -> destroying leukemic clone Ratio of difference of minor histocompatibility antigens expression between donor and pts Remission in 20-30% of AML pts after allogenic BMT (75% in CML, 40% in MDS, 15% in myeloma) 2yr survival: 19%, Tx related mortality 23% Major problem: GVHD(30-80%), marrow aplasia
Treatment of relapsed AML after allogeneic BMT with chemotherapy followed by G-CSF-primed DLI Leukemia (2004) 18 Cytoreductive chemotherapy -> G-CSF-primed DLI 2-yr overall survival: 31% CR rate Chemo DLI: DLI= 42-63%: 15-29% Post-BMT remission duration : only significant prognostic factor for overall survival High incidence of isolated extramedullary relapse