PF764 PRETRANSPLANT INCREASING RATE OF LACTATE HYDROGENASE DURING TREATMENT FREE PERIOD PREDICTS TRANSPLANT OUTCOMES FOR PATIENTS WITH MYELOID HEMATOLOGICAL MALIGNANCIES NOT IN REMISSION
Authors: Morishita T. , Ichiki T. , Okabe M. , Kawaguchi Y. , Ohbiki M. , Osaki M. , Goto M. , Araie H. , Goto T. , Ozawa Y. , Miyamura K. 
Published: June 2019

Background:

For patients (pts) with refractory myeloid hematological malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), allogeneic stem cell transplantation (allo‐SCT) is essential for cure. The long‐term outcomes for pts not in remission is previously reported as poor as 10–30% after allo‐SCT. There are several reports that pretransplant blast ratios in both bone marrow and peripheral blood are predictive markers for outcomes. Since the tumor growth of some pts with non‐complete remission (CR) status are indolent, these pts might not be evaluated accurately only by blast ratios and the assessment of tumor proliferation rates may be needed.

Aims:

For the purpose of the assessment of tumor proliferation, we evaluated the impact of pretransplant increasing rates of lactate hydrogenase (LDH) during treatment free period on long‐term transplant outcomes.

Methods:

Among 283 pts with AML or MDS who underwent allo‐SCT at our institute from 2009 to 2018, 74 pts with non‐CR status were candidates for this retrospective study. Pts with severe hepatic disorder (CTCAE grade≥3) or with their second transplant were excluded and 67 pts were eligible. We evaluated changes of patients’ LDH for 12 days (±2 days) during the latest treatment free period before conditioning therapies for allo‐SCT. Treatment free period was defined as interval of 2 weeks or more from the previous chemotherapy. Pts with no previous chemotherapies were also included.

The primary endpoint of this study was to evaluate the long‐term outcome of overall survival (OS).

Results:

Median patient age was 53 years (17–68). The risks of diseases were intermediate in 48 and high in 19 pts. Twenty‐three pts were diagnosed of AML, 32 pts of AML with myelodysplasia‐related changes and 12 pts of MDS. Transplant donor sources were as follows: bone marrow, 42 pts; peripheral blood, 16 pts; cord blood, 9 pts.

With a median follow up period of 45.9Mo, the probability of OS at 36‐months after allo‐SCT was 37.3% (95%CI, 25.4–49.2). Univariate log rank analyses showed that variables of higher increased rate of LDH (36‐months OS = 9.1%, 95%CI, 1.9–23.6, P < 0.01), absolute LDH value at conditioning chemotherapy (36‐months OS = 22.8%, 95%CI, 9.3–39.7, P = 0.029) and chemotherapy performed before treatment free period (36‐months OS = 25.0%, 95%CI, 10.9–42.0, P = 0.028) were significantly associated with poor OS. But higher blast ratio was not (36‐months OS = 29.3%, 95%CI, 15.0–45.1, P = 0.40). High disease risk index was correlated with poor OS but not significant (36‐months OS = 25.3%, 95%CI, 8.6–46.2, P = 0.051). In multivariate Cox proportional‐hazards regression models, a variable of higher increased rate of LDH only remained associated with poor OS (HR = 4.38, 95%CI, 1.73–11.08, P < 0.01).

Summary/Conclusion:

Pretransplant higher increased rate of LDH significantly predicted poor OS. Comparing to previously reported variables of blast ratio and disease risk index, higher increased rate of LDH was the solely strongest predictive marker for the long‐term outcome. We conclude that our novel assessment of tumor proliferation by evaluating pretransplant increasing LDH rates during treatment free period predicts poor long‐term transplant outcomes for patients with myeloid hematological malignancies not in remission.

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