Page 200 - 2021_12-Haematologica-web

Letters to the Editor
Figure 1. Swimmer plot. Right panel: time from allogeneic hematopoietic cell transplantation (alloHCT) to post transplant events. Left panel: time from chronic lymphocytic leukemia (CLL) diagnosis to Richter’s transformation (RT) and alloHCT. Middle panel: selected risk features. HCT-CI: HCT comorbidity index; Complex 5: complex karyotype defined as ≥5 abnormalities.12 High lactate dehydrogenase (LDH) is defined as LDH >205 U/L. Low PLT: platelet count <100x109/L.
vivors was 54 months (range: 16-92 month); median OS was not reached and median PFS was 11.2 months. Four- year OS, progression-free survival (PFS), cumulative inci- dence of non-relapse mortality (NRM) and relapse were 53%, 39%, 29% and 32%, respectively. (Figure 2A and B). The cumulative incidence of grade 2-4 and grade 3-4 acute GvHD at 6 months were 36% and 18%, respective- ly (Table 1).
As for risk factors, all four patients with low platelet counts (subjects 1, 2, 4 and 5) and six of seven patients with high LDH died within 17 months of alloHCT (sub- jects 3, 4, 5, 7, 9 and 14) (Figure 1). Due to the small num- ber of patients with high LDH and low platelet counts, these two factors were combined and considered ‘high risk’. Four-year OS was 11% in this high risk group and 74% in the standard risk group (P<0.0001) (Table 1; Figure 2C). In addition, patients who developed grade 2- 4 acute GvHD did poorly, with nine of 11 dying within 18 months (hazard ratio [HR] for OS: 3.94, P=0.016) (Figure 1; Table 1). High risk was also associated with poor PFS (4-year PFS 0% vs. 58%, P<0.0001) (Table 1; Figure 2D). Age was not a significant risk factor for OS but was significant for PFS (4-year PFS 10% for age ≥65 vs. 55% for age <65 years, P=0.006) (Table 1; Online Supplementary Figure S1A). Risk factors for NRM included the occurrence of grade 2-4 acute GvHD (HR: 7.08, P=0.017) (Table 1). Risk factors for relapse included age ≥65 years (4-year cumulative incidence 70% vs. 11%, P=0.007) and high risk (4-year cumulative incidence 56% vs. 21%, P=0.05). (Table 1; Online Supplementary Figure S1B and D). Other factors did not affect outcomes. In par- ticular, remission status (CR vs. PR), Eastern Cooperative Oncology Group performance status, HCT comorbidity index, use of targeted therapy prior to alloHCT, number of prior therapies, year of HCT, PET positivity, bulky dis-
ease, fluorescence in situ hybridization (FISH) abnormali- ties and complex karyotype did not affect outcomes.
To our knowledge, this is the largest study reporting outcomes of patients with RT who underwent alloHCT in recent years. We report favorable outcomes for these previously treated patients. Importantly, half of these patients have extended OS, reaching a plateau after 1.5 years post transplant. This suggests that some RT patients could be cured with alloHCT.
For factors that are associated with poor outcome, high risk disease (i.e., low platelet counts and/or high LDH) was significantly associated with shorter OS and PFS. Outcome for patients with standard risk at transplant was excellent (4-year OS and PFS: 74% and 58%, respec- tively) despite the fact that these patients had failed mul- tiple therapies. In contrast, few patients with high risk showed benefit from alloHCT suggesting that LDH and platelet counts together could be a sensitive marker of residual disease, since radiologic remission status based on PET/CT imaging at transplant was not predictive of outcome. In addition to these factors, advanced age was associated with poor outcome. Interestingly, use of prior targeted therapy was not associated with improved out- come. Similarly, year of transplant and number of prior therapies for CLL or for RT did not affect clinical out- come. These findings are very different from CLL patients who undergo alloHCT in the modern era13 but resemble observations made in alloHCT of de novo DLBCL,14 suggesting that disease control and sensitivity to alloHCT may be most critical for an aggressive disease like RT.
The survival outcome reported in the current study compares favorably to previously published alloHCT series in RT. The European Society for Blood and Marrow Transplantation10 (n=25, 72% RIC) reported 3-year OS
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haematologica | 2021; 106(12)