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Post-HSCT outcomes following treatment with gemtuzumab ozogamicin

Mar 10, 2021

Gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody conjugated to calicheamicin, is approved for newly diagnosed and relapsed/refractory CD33+ acute myeloid leukemia (AML). Results from the phase III ALFA-0701 trial (NCT00927498) showed improved survival rates with fractionated-dose GO plus standard chemotherapy compared with standard chemotherapy alone. However, treatment with GO has been associated with veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly when administered prior to hematopoietic stem cell transplant (HSCT).

VOD/SOS is a serious complication in patients undergoing HSCT and is thought to be a result of hepatic sinusoidal damage following conditioning therapies. More information and expert safety recommendations on GO use and VOD/SOS can be found on the AML Hub. Cécile Pautas and colleagues conducted a retrospective analysis of patients in ALFA-0701 who received HSCT as follow-up therapy and examined post-transplant outcomes and rates of VOD/SOS. Their findings are published in Bone Marrow Transplantation1 and are summarized below.

Study design

In ALFA-0701, 271 patients with untreated de novo AML were randomized to 3+7 induction with daunorubicin on Days 1–3 and cytarabine on Days 1–7, with or without GO 3 mg/m2 on Days 1–4. Subsequently, patients who achieved complete remission (CR) after induction received two consolidation courses of daunorubicin and cytarabine with or without GO on Day 1. Apart from patients with core-binding factor AML or with normal karyotype and either NPM1+/FLT3-ITDwt or CEBPA+ AML, patients who had obtained CR were allowed to progress to allogeneic HSCT (allo-HSCT). Endpoints were overall survival, post-HSCT survival, non-relapse mortality, and relapse.


Overall, 85 patients progressed to HSCT, of which 32 were initially randomized to receive GO plus standard chemotherapy and 53 initially received standard chemotherapy alone (controls). Following induction, eight patients in the control arm received GO as follow-up therapy prior to HSCT, and one patient in the GO arm proceeded to HSCT without GO. Baseline and transplant characteristics were similar between arms and are listed in Table 1.

Table 1. Patient characteristics*

Allo-HSCT, allogeneic HSCT; auto-HSCT, autologous HSCT; CR, complete remission GO, gemtuzumab ozogamicin; HSCT, hematopoietic stem cell transplant.
*Data derived from
Pautas et al.1


(n = 32)

(n = 53)

Median age, years (range)

60 (51–67)

59 (50–69)

Male, %



Cytogenetics, %



Median time from last GO dose to HSCT, days (range)

222 (64–1,215)

121 (52–753)

Time of HSCT relative to last GO dose, %
              <2 months
              ≥2 months



Timing of HSCT, %
During first CR
              After induction failure
              After relapse




Transplant type, %



Conditioning type, %
              Reduced intensity



Complete remission was achieved by 29 patients in the GO arm and 44 patients in the control arm, with a median time from first CR to HSCT of 6.4 months and 7.8 months, respectively. Three patients developed VOD/SOS prior to HSCT:

  • Two patients, both in the GO arm, experienced VOD/SOS during induction but recovered, although developed VOD/SOS again after a second HSCT.
  • A further patient in the control arm had VOD/SOS after follow-up therapy with GO and cytarabine, and also recovered.

Out of 39 patients who received GO prior to HSCT, the rate of VOD/SOS following HSCT/conditioning was 7.7% (n = 3).

  • One patient in the GO arm, who had previously discontinued GO following VOD/SOS during induction (see above), experienced a reoccurrence of VOD/SOS after a second allo-HSCT with reduced-intensity conditioning. Despite recovery within 1 month, the patient subsequently died 14.8 months after the first HSCT.
  • A second patient in the GO arm developed VOD/SOS after reduced intensity conditioning but prior to allo-HSCT, and they died within 1 month of HSCT.
  • One patient in the control arm, who received GO as follow-up therapy before HSCT, was diagnosed with VOD/SOS after autologous HSCT with myeloablative conditioning but fully recovered and was still alive 28.7 months later.

Post-transplant outcomes are shown in Table 2. Post-transplant survival, non-relapse mortality, and relapse rate were similar between the GO and control arms. Treatment with GO was not associated with a difference in overall survival in patients who received HSCT (HR, 0.97; 95% CI, 0.54–1.75; p = 0.919), however in patients who did not receive HSCT, survival was prolonged in the GO arm compared with the control arm (HR, 0.68; 95% CI, 0.48–0.97; p = 0.0333).

Table 2. Post-transplant outcomes*

CI, confidence interval; CR, complete remission; GO, gemtuzumab ozogamicin; HSCT, hematopoietic stem cell transplant; NE, not estimable; NRM, non-relapse mortality, OS, overall survival.
*Data derived from
Pautas et al.1


(n = 32)

(n = 53)

Median OS, months (95% CI)
In patients who received HSCT
              In patients who did not receive HSCT

21.4 (9.4–NE)

17.1 (7.3–NE)

3-year survival, % (95% CI)

39.4 (21.9–56.5)

44.5 (30.5–57.6)

12-month NRM, % (95% CI)

28.7 (14.1–45.2)

21.6 (11.5–33.8)

12-month relapse rate, % (95% CI)

9.4 (2.3–22.6)

31.4 (19.1–44.4)

Median post-transplant survival, months (95% CI)
              HSCT in first CR
              HSCT after induction failure/relapse

n = 17
NE (12.6–NE)
14.5 (0.9–28.1)

n = 22
19.2 (5.9–NE)
10.5 (5.3–NE)

3-year survival post-transplant, % (95% CI)
HSCT in first CR
              HSCT after induction failure/relapse

n = 15
52.9 (27.6–73.0)
21.0 (3.6–48.1)

n = 31
45.5 (24.4–64.3)
44.3 (25.8–61.2)


Fractionated-dose GO, as part of induction and consolidation chemotherapy for AML, was shown not to induce excess post-transplant VOD/SOS or mortality, with the rate of post-HSCT/conditioning VOD/SOS in patients exposed to GO similar to other retrospective analyses. The authors suggested that the low rate of VOD/SOS in their study may be due to the use of fractionated-dosing, reduced-intensity conditioning in the majority of patients, and the 2-month interval between the last GO dose and HSCT. They therefore proposed that treatment with fractionated-dose GO does not rule out the use of HSCT as a consolidation therapy option.

  1. Pautas C, Raffoux E, Lambert J, et al. Outcomes following hematopoietic stem cell transplantation in patients treated with standard chemotherapy with or without gemtuzumab ozogamicin for acute myeloid leukemia. Bone Marrow Transplant. Online ahead of print. DOI: 10.1038/s41409-020-01207-4