Gemtuzumab-Ozogamicin-Related Impaired Hemoglobin-Haptoglobin Scavenging as On-Target/Off-Tumor Toxicity of Anti-CD33 AML Therapy: A Report of Two Cases

Table 1

Summary of the five patients who had impaired hemoglobin‐haptoglobin scavenging reaction after gemtuzumab-ozogamicin therapy. The first two cases are described in detail in this paper, and the last three patients are summarized from two previous publications. In addition, Maniecki et al. [7] mentioned one adult patient, from whom clinical details were not reported.

Patient	Diagnosis	Frontline therapy	Therapy of relapse	Time from last GO to hemolysis	Infections	Symptoms during hemolysis	Outcome	Publication
Patient 1 : 21-year-old female (index patient)	Relapsed CBF-AML (BM-blasts 65%) t (8; 12), corresponding RUNX1/RUNX1T1-fusion gene. Additional mutations in PHF6, EZH2, and KDM6A. No extramedullary disease.	7 + 3 (cytarabine + daunorubicin), 3 x HD-AraC. Relapse after 2 mo.	7 + 3 (cytarabine and idarubicin) and GO (3 mg/m^2, days 1, 4, 7)	19 days	Enterococcus faecium sepsis, Clostridium difficile colitis, HHV6 viremia, HSV stomatitis	Fever, convulsions, confusion, mild diastolic hypertension	Recovered after repeated TPEs. Response to therapy: CRi, MRD-neg	Current
Patient 2 : 24-year-old female	Primary CBF-AML (BM-blasts 69%) Inv16, corresponding CBFB-MYH11-fusion gene. Axillary and inguinal lymphadenopathy.	7 + 3 (cytarabine and idarubicin) and GO (3 mg/m2 on day 4)	—	14 days	Suspected infection, blood cultures negative and virus samples negative. No deep foci of infection detected.	Fever, hypertension, bradycardia	Recovered after 3 TPEs. Response to therapy: CR, MRD 0.02%	Current
2-year-old boy	Relapsed AML M4/M5	NOPHO-AML93 + MUD-SCT. Relapse 18 mo after SCT.	FLAG and 2 doses of GO (7.5 mg/m2) at a 2-week interval	3 weeks	Staphylococcal sepsis	Abdominal pain, hypertension, persistent high fever, malaise	Recovery, but died later from PD	Maniecki et al. Blood 2000 [7]
1-year-old girl	Relapsed AML M5	NOPHO-AML 2004 with 2 doses of GO (5 mg/m^2, 2-week interval). Relapse after 3 mo.	FLAG-DaunoXome, 2 doses of GO (6 mg/m^2, 2-week interval) and NOPHO-AML 2004 induction	5 weeks	Suspected infection, blood cultures negative	Hypertension, confusion, convulsions	Did not recover from hemolytic episode and died from PD 72 days from the first GO	Maniecki et al. Blood 2000 [7]
12-year-old boy	Refractory AML	Relapse after two salvage chemotherapies	GO on days 1 and 15, dose not reported	Hemolytic samples from day 5 of GO cycle	Vancomycin-resistant Enterococcus faecium and Trichosporon asahii infections	Hypertension, multiorgan failure and need for renal replacement therapy	Did not recover from hemolysis and died 40 days after the first GO	Tesfazghi et al. Clin Chem 2018 [8]

Abbreviations. AML: acute myeloid leukemia; BM, bone marrow; CBF, core-binding factor; CR, complete remission; CRi, CR with incomplete recovery of blood counts; FLAG, fludarabine-HD-AraC-granulocyte stimulating factor; GO, gemtuzumab-ozogamicin; HD-AraC, high-dose cytarabine; HHV6, human herpes virus 6; HSV, herpes simplex virus; mo, months; MRD, minimal residual disease; MUD, matched unrelated donor; NA, not accessible; PD, progressive disease; SCT, stem cell transplant; and TPE, therapeutic plasma exchange.