-
1.
Allogeneic hematopoietic cell transplantation is equally effective in secondary acute lymphoblastic leukemia (ALL) compared to de-novo ALL-a report from the EBMT registry
Sadowska-Klasa, A., Zaucha, J. M., Labopin, M., Bourhis, J. H., Blaise, D., Yakoub-Agha, I., Salmenniemi, U., Passweg, J., Fegueux, N., Schroeder, T., et al
Bone marrow transplantation. 2024
-
-
-
Full text
-
Editor's Choice
Abstract
Secondary acute lymphoblastic leukemia (s-ALL) comprises up to 10% of ALL patients. However, data regarding s-ALL outcomes is limited. To answer what is the role of allogeneic hematopoietic cell transplantation (HCT) in s-ALL, a matched-pair analysis in a 1:2 ratio was conducted to compare outcomes between s-ALL and de novo ALL (dn-ALL) patients reported between 2000-2021 to the European Society for Blood and Marrow Transplantation registry. Among 9720 ALL patients, 351 (3.6%) were s-ALL, of which 80 were in first complete remission (CR1) with a known precedent primary diagnosis 58.8% solid tumor (ST), 41.2% hematological diseases (HD). The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between ST and HD patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL. To conclude, patients with s-ALL who received HCT in CR1 have comparable outcomes to patients with dn-ALL.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia, reported to the EBMT registry (n=9720)
Intervention
A detailed analysis cohort who were transplanted for secondary acute lymphoblastic leukaemia (s-ALL, n=80)
Comparison
Matched controls who were transplanted for de novo ALL (dn-ALL, n=80)
Outcome
The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between solid tumour and haematological disease patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL.
-
2.
A prognostic score system in adult T-cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation
Xiao, M., Zhou, J., Zhu, X., He, Y., Wang, F., Zhang, Y., Mo, X., Han, W., Wang, J., Wang, Y., et al
Bone marrow transplantation. 2024
Abstract
Adult T-cell acute lymphoblastic leukemia (T-ALL) is highly aggressive with poor prognoses, while hematopoietic stem cell transplantation (HSCT) is a curable option. However, no transplant-specific prognostic model for adult T-ALL is available. We identified 301 adult T-ALL patients who received HSCT at our hospital between 2010 and 2022. These patients were randomly assigned at a 7:3 ratio to a derivation group of 210 patients and a validation group of 91 patients. Next, we developed a prognostic risk score system for adult T-ALL with HSCT, which we named COMM, including 4 predictors (central nervous system involvement, Non-CR1 (CR2+ or NR) at HSCT, minimal residual disease (MRD) ≥ 0.01% after first induction therapy, and MRD ≥ 0.01% before HSCT). Patients were categorized into three risk groups, low-risk (0), intermediate-risk (1-4), and high-risk (5-12), and their 3-year overall survival (OS) were 87.5% (95%CI, 78-93%), 65.7% (95%CI, 53-76%) and 20% (95%CI, 10-20%; P < 0.001), respectively. The area under the subject operating characteristic curve for 2-, 3- or 5-year OS in the derivation cohort and in the validation cohort were all greater than 0.75. Based on internal validation, COMM score system proved to be a reliable prognostic model that could discriminate and calibrate well. We expect that the first prognostic model in adults T-ALL after HSCT can provide a reference of prognostic consultation for patients and families, and also contribute to future research to develop risk adapted interventions for high-risk populations.
-
3.
Long-term outcome after autologous BCR::ABL1-negative peripheral blood stem cell transplantation in adults with Philadelphia-positive acute lymphoblastic leukemia: a comparative study
Caillot, L., Leclerc, M., Sleiman, E. J. R., Sloma, I., Wagner-Ballon, O., Claudel, A., Beckerich, F., Redjoul, R., Robin, C., Parinet, V., et al
Haematologica. 2023
Abstract
Not available.
-
4.
Clinical significance of total nucleated cell count in bone marrow of patients with acute lymphoblastic leukemia who underwent allogeneic hematopoietic stem cell transplantation
Nukui, J., Tachibana, T., Miyazaki, T., Tanaka, M., Matsumoto, K., Ishii, Y., Numata, A., Nakajima, Y., Matsumura, A., Suzuki, T., et al
International journal of hematology. 2023
Abstract
The clinical implications of recipient bone marrow nucleated cell count (NCC) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unknown. We conducted a multicenter retrospective study to evaluate the clinical significance of bone marrow NCC prior to allo-HSCT in patients with acute lymphoblastic leukemia. Patients who were in remission and underwent the initial allo-HSCT were included and stratified into high- and low-NCC groups using an NCC of 10 × 10(4)/µL as the cut-off. The 3-year overall survival (OS), non-relapse mortality (NRM), and relapse rates for the high- and low-NCC groups were 51.2 vs. 84.5% (p < 0.001), 27.5 vs. 6.5% (p < 0.001), and 31.1 vs. 24.4% (p = 0.322), respectively. The high-NCC group had significantly poorer OS and higher NRM when compared with the low-NCC group. In summary, high recipient bone marrow NCC is associated with higher NRM and lower OS following allo-HSCT.
-
5.
Impact of MRD on clinical outcomes of unrelated hematopoietic stem cell transplantation in patients with Ph(+) ALL: A retrospective nationwide study
Hirabayashi, S., Kondo, T., Nishiwaki, S., Mizuta, S., Doki, N., Fukuda, T., Uchida, N., Ozawa, Y., Kanda, Y., Imanaka, R., et al
American journal of hematology. 2023
Abstract
Measurable residual disease (MRD) status before transplantation has been shown to be a strong prognostic factor in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). However, the outcomes of unrelated hematopoietic stem cell transplantation based on the MRD status have not been fully investigated. In this retrospective study, we compared the outcomes of 715 consecutive adults with Ph(+) ALL in complete remission who underwent unrelated cord blood transplantation (UCBT) (single-unit UCBT, n = 232 [4/6, 5/6, and 6/6 HLA match]), HLA-matched unrelated bone marrow transplantation (UBMT; n = 292 [8/8 HLA match]), or HLA-mismatched UBMT (n = 191 [7/8 HLA match]). In the MRD(+) cohort, adjusted 3-year leukemia-free survival rates were 59.8%, 38.3%, and 55.5% after UCBT, HLA-matched UBMT, and HLA-mismatched UBMT, respectively. In the MRD(-) cohort, the corresponding rates were 65.3%, 70.4%, and 69.7%, respectively. The MRD(+) HLA-matched UBMT group had a significantly higher risk of relapse than the MRD(+) HLA-mismatched UBMT group (hazard ratio [HR] in the MRD(+) HLA-mismatched UBMT group, 0.33; 95% confidence interval [CI] 0.15-0.74) and the MRD(+) UCBT group (HR in the MRD(+) UCBT group, 0.38; 95% CI 0.18-0.83). Furthermore, HLA-matched UBMT had a significant effect of MRD on death (HR 1.87; 95% CI 1.19-2.94), relapse or death (HR 2.24; 95% CI 1.50-3.34), and relapse (HR 3.12; 95% CI 1.75-5.57), while UCBT and HLA-mismatched UBMT did not. In conclusion, our data indicate Ph(+) ALL patients with positive MRD may benefit from undergoing UCBT or HLA-mismatched UBMT instead of HLA-matched UBMT to reduce leukemic relapse.
-
6.
Prognosis of patients with acute lymphoblastic leukaemia relapsing after allogeneic stem cell transplantation
Ferra Coll, C., Morgades de la Fe, M., García, L. P., Vaz, C. P., Heras Fernando, M. I., Bailen Almorox, R., Garcia Cadenas, I., Calabuig Muñoz, M., Ripa, T. Z., Zanabili Al-Sibai, J., et al
European journal of haematology. 2023
Abstract
The outcomes of patients with acute lymphoblastic leukaemia (ALL) presenting relapse after allogeneic stem cell transplant (Allo-SCT) are poor, with few data available in this setting. OBJECTIVE AND METHODS To evaluate the outcomes of patients with ALL presenting relapsed after allo-SCT, we performed a retrospective study including 132 from 11 centers in Spain. RESULTS Therapeutic strategies consisted of palliative treatment (n=22), chemotherapy (n=82), tyrosine kinase inhibitors (n=26), immunotherapy with inotuzumab and/or blinatumumab (n=19), donor lymphocyte infusions (n=29 pts), second allo-SCT (n=37) and CAR T therapy (n=14). The probability of overall survival (OS) at 1 and 5 years after relapse was 44% (95%CI: 36%; 52%) and 19% (95% CI: 11%; 27%). In the 37 patients undergoing a second allo-SCT, the 5-year estimated OS probability was 40% [22%; 58%]. Younger age, recent allo-SCT, late relapse, 1st complete remission at 1st allo-SCT and chronic graft-versus-host disease confirmed their positive impact on survival in the multivariable analysis. CONCLUSION Despite the poor prognosis of patients with ALL presenting relapse after a first allo-SCT, some can be satisfactorily rescued and a second allo-SCT still remains a valid option for selected patients. Moreover, emerging therapies really might improve ALL patients outcome when relapsing after an allo-SCT .
-
7.
Outcome of hematopoietic stem cell transplantation in pediatric patients with acute lymphoblastic leukemia not in remission enrolled in JACLS ALL-02
Yano, M., Ishida, H., Hara, J., Kawaguchi, H., Ito, E., Moriya-Saito, A., Hashii, Y., Deguchi, T., Miyamura, T., Sato, A., et al
International journal of hematology. 2023
Abstract
Hematopoietic stem cell transplantation (HSCT) is only indicated for acute lymphoblastic leukemia (ALL) patients for whom other treatments are unlikely to be curative. However, outcomes of patients not in complete remission (CR) at HSCT remain very poor. To improve the outcomes of patients receiving HSCT, it is important to obtain detailed clinical information about patients with ALL receiving HSCT in CR and not in CR. Patients enrolled in the Japan Association of Childhood Leukemia Study ALL-02 who underwent HSCT and were not in CR (non-CR patients, n = 55) were examined. The 1-year overall survival (OS) rate of non-CR patients was 27.3%. Compared with CR patients, non-CR patients experienced very early and early relapse significantly more frequently and had poorer prognostic factors. Most interestingly, high hyperdiploid (HHD) patients showed an excellent 1-year OS of 80%. In addition, long-term survival among surviving HHD patients was longer than 5 years. All eight patients who survived after undergoing HSCT while not in CR were younger than 10 years at initial diagnosis and were negative for central nervous system involvement. While limited, these results suggest that a subset of patients may benefit from HSCT while not in CR.
-
8.
Next-Generation Sequencing-Based MRD in Adults with ALL Undergoing Hematopoietic Cell Transplantation
Liang, E. C., Dekker, S. E., Sabile, J. M. G., Torelli, S., Zhang, A., Miller, K., Shiraz, P., Hayes-Lattin, B., Leonard, J. T., Muffly, L.
Blood advances. 2023
Abstract
Measurable residual disease (MRD) is an adverse prognostic factor in adult acute lymphoblastic leukemia (ALL) patients undergoing hematopoietic cell transplantation (HCT). Next-generation sequencing (NGS) can detect MRD with a sensitivity of 10-6, but the prognostic value of NGS-based MRD in adult ALL patients undergoing HCT remains minimally studied. To evaluate the prognostic value of NGS-based MRD in adult ALL patients undergoing HCT. Patients with ALL aged ≥18 years old who underwent allogeneic HCT at Stanford University or Oregon Health & Science University between January 2014-April 2021 and who were evaluated for MRD using the NGS-based clonoSEQ assay were included in this study. MRD was assessed pre-HCT (MRDpre) and for up to 1 year post-HCT (MRDpost). Patients were followed for leukemia relapse and survival for up to 2 years post-HCT. 158 patients had a trackable clonotype for MRD monitoring. The cumulative incidence of relapse was increased at all levels of MRDpre, including in patients who had low MRDpre of <10-4 (HR 3.56, 95% CI, 1.39-9.15). In multivariable analysis, MRDpre level remained significantly prognostic; however, detectable MRDpost was the strongest predictor of relapse (HR 4.60, 95% CI, 3.01-7.02). In exploratory analyses limited to B-cell ALL patients, detection of post-HCT IgH MRD clonotypes, rather than non-IgH MRD clonotypes, were associated with relapse. In this analysis across two large transplant centers, we found that detection of MRD by NGS at a level of 10-6 offers significant prognostic value in adults with ALL undergoing HCT.
-
9.
A pilot study of implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia
Afanaseva, K. S., Bakin, E. A., Smirnova, A. G., Barkhatov, I. M., Gindina, T. L., Moiseev, I. S., Bondarenko, S. N.
Scientific reports. 2023;13(1):16790
Abstract
The posttransplant relapse in Ph-positive ALL increases the risk of death. There is an unmet need for instruments to predict the risk of relapse and plan prophylaxis. In this study, we analyzed posttransplant data by machine learning algorithms. Seventy-four Ph-positive ALL patients with a median age of 30 (range 18-55) years who previously underwent allo-HSCT, were retrospectively enrolled. Ninety-three percent of patients received prophylactic/preemptive TKIs after allo-HSCT. The values of the BCR::ABL1 level at serial assessments and over variables were collected in specified intervals after allo-HSCT. They were used to model relapse risk with several machine-learning approaches. GBM proved superior to the other algorithms and provided a maximal AUC score of 0.91. BCR::ABL1 level before and after allo-HSCT, prediction moment, and chronic GvHD had the highest value in the model. It was shown that after Day + 100, both error rates do not exceed 22%, while before D + 100, the model fails to make accurate predictions. As a result, we determined BCR::ABL1 levels at which the relapse risk remains low. Thus, the current BCR::ABL1 level less than 0.06% in patients with chronic GvHD predicts low risk of relapse. At the same time, patients without chronic GVHD after allo-HSCT should be classified as high risk with any level of BCR::ABL1. GBM model with posttransplant laboratory values of BCR::ABL1 provides a high prediction of relapse after allo-HSCT in the era of TKIs prophylaxis. Validation of this approach is warranted.
-
10.
Is Mixed Chimerism Post-allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoid Leukemia a Prognostic Factor for Relapse?
Khan, S., AlSaif, Z., Siddiqui, K., AlSaedi, H., Al-Ahmari, A., Al-Jefri, A., Ghemlas, I., AlAnazi, A., Ayas, M.
Hematology/oncology and stem cell therapy. 2023;17(1):72-78
Abstract
Hematopoietic stem cell transplantation (HSCT) has been considered curative for children with high-risk acute leukemia (ALL), offering better survival. Short tandem repeat has been used as a marker of chimerism status after HSCT. The appearance of recipient cells >1% post-allogeneic stem cell transplant is defined as mixed chimerism (MC). Chimeric studies post-HSCT are dynamic. This study aimed to investigate the significance of recipient cells in post-HSCT pediatric ALL patients as a predictor of relapse of their primary disease. The rate of MC was 51.4% (19 out of 37 recipients). It was 48.6% (n = 18) during Day+100 and 12.9% (4 out of 31 recipients) during post-Day+100 follow-up until two years. No significant association was noted between MC and all grade overall acute graft-versus-host disease. A mortality rate of 35.1% (n = 13) and a median follow-up of 56.9 months (95% CI: 39.7-74.2) were observed for all but four (16.7%) of the survivors in remission. Regarding causes of death, transplant-related mortality was recorded in only 2 of 13 expired patients (15.4%); both succumbed to sepsis. No significant association was found between MC and primary causes of death. The cumulative probability of five-year overall survival and event-free survival was not found to be statistically significantly different for MC (≤1.0% vs. > 1.0%). In conclusion, our data did not show MC testing alone as an effective prognostic marker for detecting relapse; molecular and flow cytometric analyses should be considered in children with ALL post-HSCT for monitoring relapse.