Optimized BEAC conditioning regimen improves clinical outcomes of autologous hematopoietic stem cell transplantation in non-Hodgkin lymphomas

Patient characteristics

Patient baselines before and after propensity score matching (PSM) are summarized in Supplementary Table S1 and Table 1, respectively. There were 82 patients in the AD-BEAC group and 59 patients in the SD-BEAC group before PSM, and 52 patients in each group were successfully matched. In both groups, most patients were stage III–IV and had an IPI score of 3 or more. There was no difference in clinical characteristics between the two groups (P ˃ 0.05).

Table 1 patient baseline after propensity scoreStem cell mobilization and hematologic recovery

The median count of mononuclear cells (MNCs) was 8.97 × 108/kg (range, 2.17–25.28) in the AD-BEAC group and 9.06 × 108/kg (range, 2.2–19.43) in the SD-BEAC group (P = 0.569). The median infused CD34 + cell count was 5.61 × 106/kg (range, 1.78–18.8) in the AD-BEAC group and 4.7 × 106/kg (range, 1–19.53) in the SD-BEAC group (P = 0.068). No significant difference was found in either MNC or CD34 + cell counts between the two groups.

Almost all patients had successful ANC and PLT reconstitution. The median time to reconstitution of ANC in the two groups was 11 days (range, 8–20 and 8–18, P = 0.845). The median time to reconstitution of PLTs in the two groups was 14 days and 11 days (range, 8–29 and 8–22, P = 0.267).

Response

The transplantation efficacy was assessed 3 months after transplantation, and 47 patients in the AD-BEAC group achieved CR after transplantation, of which 19 patients with PR before transplantation achieved CR after transplantation. In the SD-BEAC group, 39 patients achieved CR after transplantation, and 13 patients with PR before transplantation achieved CR after transplantation. The CR rate of the AD-BEAC conditioning regimen was higher than that of the SD-BEAC conditioning regimen (90.4% vs. 75.0%, P = 0.038).

Progression/relapse rate

Since all patients achieved CR/PR before transplantation, we analyzed relapse/progression rates at 3 and 5 years after transplantation. The relapse/progression rate in the AD-BEAC group was much lower than that in the SD-BEAC group (3-year 8% vs. 20%, 5-year 10% vs. 26%, P = 0.026, HR 0.3324, 95% CI 1.223–7.399) (Fig. 1). Relapse/progression typically occurred within 2 years after transplantation and mainly occurred in patients who did not achieve CR before transplantation.

Fig. 1figure 1

Cumulative relapse rate of SD-BEAC and AD-BEAC conditioning regimen

Survival analysis

The median follow-up time was 85 months in 104 patients after PSM, and the AD-BEAC group had a higher OS and PFS than the SD-BEAC group (5-year OS 82.7% vs. 67.3%, P = 0.039, HR 0.4464, 95% CI 0.2128–0.9367; 5-year PFS 76.9% vs. 57.7%, P = 0.039, HR 0.4881, 95% CI 0.2489–0.9570) (Fig. 2a, b). In the SD-BEAC group, 15 of 21 patients with recurrence and progression received salvage chemotherapy or targeted therapy, and 4 of them were still alive by the end of follow-up. In the AD-BEAC group, 6 of 8 patients with recurrence and progression received salvage chemotherapy or targeted therapy, and 3 of them were still alive by the end of follow-up.

Fig. 2figure 2

a Overall survival (OS) of SD-BEAC and AD-BEAC conditioning regimen, b progression-free survival (PFS) of SD-BEAC and AD-BEAC conditioning regimen

We conducted subgroup analysis on different types of lymphoma. For patients with untreated lymphoma, we found that the AD-BEAC group had a higher OS and PFS than the SD-BEAC group (5-year OS 90.2% vs. 72.5%, P = 0.023, HR 0.2948, 95% CI 0.1139–0.7631; 5-year PFS 87.8% vs. 62.5%, P = 0.013, HR 0.2985 95% CI 0.1241–0.7180) (Fig. 3a, b). However, for relapsed/refractory NHL, there was no significant difference in OS and PFS between the AD-BEAC and SD-BEAC groups (5-year OS 54.5% vs. 50.0%, P = 0.581, HR 0.7211, 95% CI 0.2205–2.358; 5-year PFS 36.4% vs. 41.7%, P = 0.773, HR 0.8603, 95% CI 0.3009–2.460) (Fig. 3c, d). For patients with B-cell lymphoma, there was no significant difference between the AD-BEAC group and the SD-BEAC group in OS and PFS (5-year OS 88.9% vs. 75.0%, P = 0.107, HR 0.3588, 95% CI 0.1156–1.113; 5-year PFS 85.2% vs. 68.8%, P = 0.116, HR 0.4085, 95% CI 0.1433–1.165) (Fig. 4a, b). For the patients with T- and NK-cell lymphoma, we found a similar outcome (5-year OS 76.0% vs. 55.0%, P = 0.137, HR 0.4738, 95% CI 0.1766–1.271; 5-year PFS 68.0% vs. 40.0%, P = 0.111, HR 0.4937, 95% CI 0.2035–1.198) (Fig. 4c, d).

Fig. 3figure 3

a Overall survival (OS) of newly diagnosed high-risk NHL, b progression-free survival (PFS) of newly diagnosed high-risk NHL, c OS of relapse/refractory NHL, d PFS of relapse/refractory NHL

Fig. 4figure 4

a Overall survival (OS) of B-cell lymphoma, b progression-free survival (PFS) of B-cell lymphoma, c OS of T- and NK-cell lymphoma, d PFS of T- and NK-cell lymphoma

Univariate and multivariate analyses

Univariate and multivariate analyses were conducted on conditioning regimen, age, disease type, disease stage, IPI scores, time from diagnosis to ASCT, chemotherapy cycles before ASCT, disease status before ASCT and newly diagnosed or relapsed/refractory disease. The univariate analysis showed that the disease type influenced PFS but not OS; additionally, conditioning regimen, disease status before ASCT, and newly diagnosed or relapsed/refractory disease influenced both OS and PFS (P < 0.05). However, the multivariate analysis showed that only the conditioning regimen influenced both OS and PFS (Tables 2 and 3).

Table 2 Univariate and multivariate analysis of the overall survivalTable 3 Univariate and multivariate analysis of the progression-free survivalToxicity

Major transplantation-related complications are summarized in Table 4. Fever, vomiting, diarrhea, and hepatobiliary disorders were the most common nonhematological toxicities. The AD-BEAC group had a lower incidence of mucositis oral (5.8% vs. 23.1%, P = 0.023) and cardiac disorders (1.9% vs. 15.3%, P = 0.048). mucositis oral in the AD-BEAC group were all grade I–II, and 5 of 12 patients with mucositis oral in the SD-BEAC group were grade III. A total of 8 patients in the SD-BEAC group experienced cardiotoxicities, including 2 cases of grade I atrial fibrillation, 2 cases of grade I palpitations, 1 case of grade I heart failure, 1 case of grade I pericardial effusion, and 2 cases of grade III heart failure. However, only 1 case of grade I atrial fibrillation occurred in the AD-BEAC group. There was no difference for other adverse events. The TRM in both the AD-BEAC and SD-BEAC groups was 3.8% (2/52). The rate of secondary malignancies between the two groups was 1.9% (1/52); one patient in the AD-BEAC group developed lung cancer 4 years after transplantation, and one patient in the SD-BEAC group developed parotid gland cancer 5 years after transplantation.

Table 4 Transplant-related toxicity

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