1.
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.
2.
A decision analysis for unrelated bone marrow transplantation or immediate cord blood transplantation for patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission: Unrelated BMT or immediate CBT for Ph-negative ALL
Kako, S., Hayakawa, F., Miyamura, K., Tanaka, J., Imai, K., Kanda, J., Morishima, S., Uchida, N., Doki, N., Ikegame, K., et al
Transplantation and cellular therapy. 2021
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Abstract
BACKGROUND A human leucocyte antigen (HLA)-matched relative is the first-choice donor for patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1). The most promising alternative donor is thought to be an HLA-matched unrelated donor (MUD) in patients who do not have an HLA-matched related donor. Cord blood transplantation (CBT) is one of alternative options. Higher rates of engraftment failure and non-relapse mortality are big problems, but the ready availability of cord blood can be an advantage because patients can immediately undergo transplantation before progression. OBJECTIVE To determine an appropriate alternative donor in patients with Ph-negative ALL in CR1, who do not have HLA-matched relatives. STUDY DESIGN Decision analyses using a Markov model were performed to compare immediate CBT, in which CBT was performed at 1 month after the achievement of CR1, with elective unrelated bone marrow transplantation (uBMT) from 8/8 MUD (8/8 uBMT) or uBMT from 7/8 MUD (7/8 uBMT), in which uBMT was performed at 4 months, in patients aged 16-55 years with Ph-negative ALL in CR1 who did not have HLA-matched relatives. We constructed a decision tree as described in Figure 1. The cycle length was set at 3 months, and analyses were performed for 19 cycles for uBMT and 20 cycles for CBT, which resulted in evaluation of the 5-year life expectancy after both decisions. Transition probabilities and utilities were estimated from prospective and retrospective Japanese studies and the registry database of Japan as summarized in Table 1. Subgroup analyses were performed according to risk stratification on the basis of the white blood cell count and cytogenetics at the diagnosis, and according to age stratification with a cutoff of 25 years. One-way sensitivity analyses for TPs and utilities were also performed. RESULTS The baseline analyses showed that the decision to perform 8/8 uBMT or 7/8 uBMT gave superior results, with quality-adjusted life years (QALYs) of 2.86, 2.84, and 2.75 in 8/8 uBMT, 7/8 uBMT, and CBT, respectively. One-way sensitivity analyses showed that the results of the baseline analyses were reversed if the probabilities of non-relapse mortality (NRM) in CBT improved. Subgroup analyses showed the similar results in lower-aged, higher-aged, and high-risk patients. However, QALY in 8/8 uBMT was worse than that in CBT in standard-risk patients. In one-way sensitivity analyses, the probabilities of NRM in uBMT and CBT affected the baseline results in all analyses except for comparisons between 8/8 uBMT and CBT in lower-aged and high-risk patients. In these 2 populations, the superiority of 8/8 uBMT was consistently demonstrated throughout the entire one-way sensitivity analyses. CONCLUSION For patients with Ph-negative ALL in CR1 who decide to undergo transplantation from an alternative donor, elective uBMT from either 8/8 MUD or 7/8 MUD is expected to give a better outcome than immediate CBT. However, CBT is a viable option, and improvements to reduce the probabilities of NRM in CBT may change these results.
PICO Summary
Population
Outcomes of patients identified from the Japan Transplant Registry Unified Management Program (TRUMP) database with Philadelphia chromosome-negative acute lymphoblastic leukaemia (Ph-negative ALL) age 16 to 55 years who underwent a first unrelated bone marrow transplantation (uBMT) in Japan (n= 327)
Intervention
Decision tree analysis using a Markov model comparing unrelated bone marrow transplantation (uBMT) to upfront cord blood transplantation, as follows:
Comparison
Comparison of 8/8 matched unrelated donor (MUD) transplant (n=163), 7/8 MUD (n=98) or Cord blood transplantation (CBT) with a single unit (n=66)
Outcome
The baseline analyses showed that the decision to perform 8/8 uBMT or 7/8 uBMT gave superior results, with quality-adjusted life years (QALYs) of 2.86, 2.84, and 2.75 in 8/8 uBMT, 7/8 uBMT, and CBT, respectively. One-way sensitivity analyses showed that the results of the baseline analyses were reversed if the probabilities of non-relapse mortality (NRM) in CBT improved. Subgroup analyses showed the similar results in lower-aged, higher-aged, and high-risk patients. However, QALY in 8/8 uBMT was worse than that in CBT in standard-risk patients. In one-way sensitivity analyses, the probabilities of NRM in uBMT and CBT affected the baseline results in all analyses except for comparisons between 8/8 uBMT and CBT in lower-aged and high-risk patients. In these 2 populations, the superiority of 8/8 uBMT was consistently demonstrated throughout the entire one-way sensitivity analyses.