Phase 1/2 Trial of CLAG-M with Dose-Escalated Mitoxantrone in Combination with Fractionated-Dose Gemtuzumab Ozogamicin for Newly Diagnosed Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms.

Gemtuzumab ozogamicin (GO) improves outcomes when added to intensive AML chemotherapy. A meta-analysis suggested the greatest benefit when combining fractionated doses of GO (GO3) with 7 + 3. To test whether GO3 can be safely used with high intensity chemotherapy, we conducted a phase 1/2 study of cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (CLAG-M) in adults with newly diagnosed AML or other high-grade myeloid neoplasm (NCT03531918).

Targeting the membrane-proximal C2-set domain of CD33 for improved CD33-directed immunotherapy.

There is increasing interest in targeting CD33 in malignant and non-malignant disorders. In acute myeloid leukemia, longer survival with the CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO) validates this strategy. Still, GO benefits only some patients, prompting efforts to develop more potent CD33-directed therapeutics.

Accuracy of SIE/SIES/GITMO Consensus Criteria for Unfitness to Predict Early Mortality After Intensive Chemotherapy in Adults With AML or Other High-Grade Myeloid Neoplasm.

Purpose: With increasing therapeutic alternatives available, there is growing interest in tools that accurately identify patients most suitable for intensive acute myeloid leukemia (AML) chemotherapy. Nowadays, conceptual criteria proposed by an Italian panel of experts are widely used for this purpose. How accurately these Ferrara criteria predict fitness for intensive chemotherapy is unknown.

Number of courses of induction therapy independently predicts outcome after allogeneic transplantation for acute myeloid leukemia in first morphological remission.

Whether the number of chemotherapy cycles required to obtain a first morphological remission affects prognosis of patients with acute myeloid leukemia (AML) remains controversial. To clarify how achievement of early remission might influence outcome of allogeneic hematopoietic cell transplantation (HCT), we studied 220 consecutive adults with AML in first morphological remission who underwent transplantation after myeloablative or nonmyeloablative conditioning to investigate how the number of standard- or high-dose induction courses required to achieve remission impacted post-HCT outcome. Three-year estimates of overall survival were 65% (95% confidence interval [CI] 56% to 73%), 56% (95% CI, 43% to 67%), and 23% (95% CI, 6% to 46%) for patients requiring 1 course, 2 courses, or >2 courses of induction therapy; corresponding relapse estimates were 24% (95% CI, 17% to 31%), 43% (95% CI, 31% to 55%), and 58% (95% CI, 30% to 78%), respectively.