Peripheral blood parameter abnormalities precede therapy-related myeloid neoplasms after autologous transplantation for lymphoma

Abstract

Background: Therapy-related myeloid neoplasms (t-MN) are a leading cause of nonrelapse mortality after autologous peripheral blood stem cell transplantation (aPBSCT) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphomas (NHL). t-MN patients treated at an earlier stage of disease evolution have a better prognosis, and this presents a need to identify patients at risk for t-MN.

Methods: Using a prospective longitudinal study design, this study evaluated peripheral blood parameters pre-aPBSCT and on day 100, at 6 months, 1 year, 2 years, and 3 years in 304 patients treated with aPBSCT. The relation between peripheral blood parameters and subsequent development of t-MN was examined, and nomograms were developed to identify patients at risk for t-MN.

Results: Twenty-one patients developed t-MN at a median of 1.95 years post-aPBSCT. Hemoglobin, hematocrit, white blood cell, and platelet counts were lower among patients who developed t-MN compared to those who did not; these differences appeared soon after aPBSCT, persisted, and preceded development of t-MN. Older age at aPBSCT (hazard ratio [HR]_{per_year_increase} = 1.08, P = .007), exposure to total body irradiation (TBI) (HR = 2.90, P = .04), and low 100-day platelet count (HR_{increase_per_unit_decline_in_PLT} = 1.01, P = .002) predicted subsequent t-MN. These parameters and primary diagnosis allowed identification of patients at high risk of t-MN (eg, an HL patient undergoing aPBSCT at the age of 70 years with TBI and with a day 100 PLT between 100,000 and 150,000 would have a 62% probability of developing t-MN at 6 years post-aPBSCT).

Conclusions: Abnormalities in peripheral blood parameters can identify patients at high risk for t-MN after aPBSCT for HL or NHL, allowing opportunities to personalize close surveillance and possible disease-modifying interventions.

Keywords: autologous peripheral blood stem cell transplantation; lymphoma; peripheral blood parameters; therapy-related myeloid neoplasms.

Figure 1.

Temporal trends in peripheral blood parameters by t-MN status. Error bars reflect standard deviation Figure 1A: RDW; Figure 1B: hematocrit; Figure 1C: hemoglobin; Figure 1D: MCV; Figure 1E: WBC; Figure 1F: platelet count.

Figure 1.

Temporal trends in peripheral blood parameters by t-MN status. Error bars reflect standard deviation Figure 1A: RDW; Figure 1B: hematocrit; Figure 1C: hemoglobin; Figure 1D: MCV; Figure 1E: WBC; Figure 1F: platelet count.

Figure 1.

Temporal trends in peripheral blood parameters by t-MN status. Error bars reflect standard deviation Figure 1A: RDW; Figure 1B: hematocrit; Figure 1C: hemoglobin; Figure 1D: MCV; Figure 1E: WBC; Figure 1F: platelet count.

Figure 1.

Temporal trends in peripheral blood parameters by t-MN status. Error bars reflect standard deviation Figure 1A: RDW; Figure 1B: hematocrit; Figure 1C: hemoglobin; Figure 1D: MCV; Figure 1E: WBC; Figure 1F: platelet count.

Figure 1.

Temporal trends in peripheral blood parameters by t-MN status. Error bars reflect standard deviation Figure 1A: RDW; Figure 1B: hematocrit; Figure 1C: hemoglobin; Figure 1D: MCV; Figure 1E: WBC; Figure 1F: platelet count.

Figure 1.

Temporal trends in peripheral blood parameters by t-MN status. Error bars reflect standard deviation Figure 1A: RDW; Figure 1B: hematocrit; Figure 1C: hemoglobin; Figure 1D: MCV; Figure 1E: WBC; Figure 1F: platelet count.

Figure 2A.

Risk prediction nomogram for t-MN post-aPBSCT for HL or NHL, incorporating baseline factors: age at aPBSCT (y), primary diagnosis (HL or NHL), and exposure to TBI (no or yes).

Figure 2B.

Risk prediction nomogram in a patient with t-MN after autologous BMT for HL. A line is drawn downward from the value of each category to the score line. The points are then added to determine the total score and a line is drawn upward to find the risk of t-MN. T-MN probability estimation: age at aPBSCT: 60y – score=70; diagnosis: HL – score=10; TBI: yes – score=30. Total score=110, with a t-MN probability at 3y of 32% and at 6y of 42%.

Figure 3A.

Risk prediction nomogram for t-MN incorporating baseline factors and day 100 peripheral blood parameters: age at aPBSCT (y), primary diagnosis (HL or NHL), exposure to TBI (no or yes), and Day 100 PLT (<50; 50–100; 100–150; >150).

Figure 3B.

Risk prediction nomogram for t-MN using baseline and day 100 data. T-MN probability estimation: age at aPBSCT: 70y – score=86; diagnosis: HL – score=19; TBI: yes – score=26; PLT at D100: 100–150 – score=16. Total score=130, with a t-MN probability at 3y of 46% and at 6y of 62%.