2022 EBMT Celebrities Comment on Professor Jiang Erlie: Advances in Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a common hematological malignancy in adults, and its long-term survival rate is significantly lower than that of childhood ALL and other types of leukemia
.

Despite many advances in adult ALL treatment in recent years, allogeneic hematopoietic stem cell transplantation (allo-HCT) still plays a key role in the treatment of adult ALL patients
.

However, relapse and non-relapse mortality is an important issue
.

Italian scholars conducted a retrospective real-world study to investigate the effect of allo-HCT on overall survival (OS), disease-free survival (DFS) and non-relapse mortality in adult ALL patients
.

The study was selected as a poster presentation at the 48th European Society of Blood and Marrow Transplantation (EBMT) annual meeting this year.
Yimaitong specially invited Professor Jiang Erlie from the Hospital of Hematology, Chinese Academy of Medical Sciences to comment on this study and the progress of allo-HCT in the treatment of ALL
.

Methods: The study included adult patients with B-ALL (Ph+/-) and T-ALL (n=133) who underwent allo-HCT at 3 Italian bone marrow transplant centers between July 2003 and July 2020
.

Multivariate analysis of pre-allo-HCT (ALL phenotype, white blood cell count [WBC] at diagnosis, number of complete remissions [CR]), allo-HCT correlation (EBMT score, donor type) and post allo-HCT (plant resistance host disease [GVHD], minimal residual leukemia [MRD]) to assess the prognosis of patients
.

The observation period ends in October 2020
.

RESULTS: Among 133 patients with a median age of 40 years (range: 18-70 years), there were 66 patients with Ph- B-ALL, 33 patients with Ph+ B-ALL, and 34 patients with T-ALL
.

The median follow-up was 18.
5 months (range: 0.
9-187.
5 months)
.

The OS rate was 47.
4%, and the median OS was 37.
4 months (range: 0.
9-187.
5 months); the DFS rate was 67.
7%, and the median DFS was not reached
.

The recurrence mortality rate was 24%, and the non-relapse mortality rate was 28.
6%
.

According to univariate analysis, T-ALL patients showed a trend toward better DFS (P = 0.
09) compared with B-ALL patients (P = 0.
09) and MRD-negative patients before allo-HCT (P = 0.
08) (A)
.

The number of CRs before allo-HCT (CR1 vs CR>1) had no effect on DFS (P=0.
08)
.

Match-matched unrelated donors tended to have significantly better DFS than patients with matched-related related donors (P=0.
07) (B)
.

The DFS trend was significantly better in patients with GVHD (P=0.
002)
.

Among B-ALL patients, those with WBC>30.
000/mmc at diagnosis had a negative effect (P=0.
09)
.

Immunophenotype MRD-negative Ph-B-ALL versus T-ALL patients tended to have better DFS at +90 days after allo-HCT (P=0.
005) (C)
.

Ph+ B-ALL patients who achieved major molecular remission had a trend toward better DFS at day +21 (P=0.
003) (D)
.

Patients with EBMT score ≥4 had lower OS and non-relapse mortality (P=0.
01)
.

CONCLUSIONS This real-world study suggests that in adult ALL patients, allo-HCT is effective, although significantly associated with transplant-related mortality predicted by the EBMT score
.

Negative MRD after Allo-HCT (+90 days) and achieving major molecular remission (+21 days) predicted good prognosis in Ph- B-ALL, T-ALL, and Ph+ B-ALL patients, respectively
.

Professor Jiang Erlie commented that allo-HCT is mainly used for the treatment of ALL patients with high-risk CR1 and ≥CR2.
After treatment, the long-term survival rate of high-risk CR1 patients can reach 40-60% [2]
.

Homozygous sibling donors are often the first choice, and in the absence of homozygous sibling donors, unrelated donors and haploid transplantation can be an effective alternative because of the stronger graft-versus-leukemia (GVL) effect
.

Two EBMT studies have shown that [3-4], haploid transplantation has no significant difference in OS, leukemia-free survival (LFS), and GVHD-relapse-free survival (GRFS) compared with full sibling donors.
However, it can reduce recurrence rate (RI) and increase non-relapse-related mortality (NRM).
Haploid transplantation has no difference in OS, LFS, RI, NRM, aGVHD and cGVHD incidence compared with unrelated donor transplantation
.

In addition, it is very important to monitor MRD both before and after transplantation in patients with B-ALL or T-ALL [5]
.

MRD is not only one of the prognostic factors affecting ALL recurrence and survival, but MRD monitoring before transplantation can be used to guide the choice of treatment after CR [6]
.

For example, a study of clinical data from our center [7] showed that, in Ph+ ALL patients, autologous hematopoietic stem cell transplantation (ASCT) is an effective consolidation treatment option for Ph+ ALL patients with s3CMR after chemotherapy, which is comparable to allo- HCT efficacy is comparable; allo-HCT significantly reduces recurrence in patients who do not achieve s3CMR
.

At the same time, consistent with the results of previous studies [8-9], this study [1] also confirmed that post-transplant MRD was significantly associated with recurrence and LFS
.

Some studies[8-9] believe that the post-transplant MRD level is more predictive of the risk of recurrence than the pre-transplant MRD level.
For patients with higher pre-transplant MRD levels, if they achieve MRD-negative in the early post-transplant period and maintain it for 1 year, it is also possible to obtain long-term results.
survive
.

Post-transplantation MRD-positive patients also need preemptive treatment when the tumor burden is still low
.

This study[1] and other studies[10-14] also proposed that in addition to MRD, risk factors that may affect post-transplant OS and LFS include conditioning regimens including TBI, I/II aGVHD and cGVHD, and WBC at diagnosis.
High (B-ALL: ≥30×109/L, T-ALL: ≥100×109/L), CR status, EBMT score,
etc.

In addition, this study[1] found that the number of CRs (CR1 vs CR>1) before allo-HCT had no effect on DFS, which may be related to the long-term survival of allo-HCT ALL patients with MRD-negative CR2 and above before transplantation [15] related
.

The new tyrosine kinase inhibitors (such as flumatinib, etc.
), CAR-T, belintuumab and other treatment regimens that have appeared in recent years are all effective in dealing with relapsed/refractory conditions before and after transplantation and in clearing MRD.
It is fruitful, thereby improving patient survival and bringing new opportunities and challenges to allo-HCT [16]
.

Professor Jiang Erlie Chief Physician, Doctoral Supervisor Director of Stem Cell Transplantation Center, Hematology Hospital, Chinese Academy of Medical Sciences Member of the Hematology Branch of the China Association for the Promotion of International Exchanges in Healthcare, Member of the Transplant Infection Academic Working Committee of the Hematology Branch of the Chinese Geriatrics Association, Vice Chairman of the Tianjin Society of Hematology and Regenerative Medicine, Standing Committee Member of the Hematology Professional Committee of the Tianjin Anti-aging Society, Tianjin Medical Member of the Hematology Branch of the Association of Integrative Chinese and Western Medicine Committee of the Organ Transplantation Branch of the Tianjin Medical Association Member of the Hematologist Branch of the Tianjin Medical Association Reference: 1.
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Alzetta, C.
Borghero, IM Cavattoni, et al.
ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: A MULTICENTER RETROSPECTIVE STUDY.
The 48th Annual Meeting of the EBMT.
Abstract P535.
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Khaled SK, Thomas SH, Forman S J.
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3.
Shem-Tov N, Peczynski C, Labopin M, et al.
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4.
Nagler A, Labopin M, Houhou M, et al.
Outcome of haploidentical versus matched sibling donors in hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation[J].
J Hematol Oncol.
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Comparison of autologous and allogeneic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia[J].
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Blood Advances, 2019, 3(21): 3393–3405.
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Greil C, Engelhardt M, Ihorst G, et al.
al.
Prognostic factors for survival after allogeneic transplantation in acute lymphoblastic leukemia[J].
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Yeshurun ​​M, D Weisdorf, Rowe JM,et al.
The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia[J].
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Jing Wang, Xiaojun Huang, Bin Jiang, et al.
Ph chromosome in adults Analysis of prognostic factors in patients with negative acute lymphoblastic leukemia[J].
Chinese Journal of Hematology, 2015,36(1):10-15.
13.
Yanada M, Konuma T, Yamasaki S, et al.
The differential effect of disease status at allogeneic hematopoietic cell transplantation on outcomes in acute myeloid and lymphoblastic leukemia[J].
Annals of Hematology, 2021:1-11.
14.
Numata A, Tanaka M, Matsumoto K, et al.
Validation of the European Group for Blood and Marrow Transplantation (EBMT) risk score in patients receiving allogeneic hematopoietic stem cell transplantation at a single center in Japan[J].
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15.
Cassaday RD, Alan Potts D, Stevenson PA, et al.
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16.
Defilipp Z, Advani AS, Bachanova V, et al.
Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy[J].
Biology of Blood and Marrow Transplantation, 2019, 25(11):2113-2123.
Review : Professor Jiang Erlie Typesetting: Quinta pokes "read the original text", let's make progress togetherUpdated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy[J].
Biology of Blood and Marrow Transplantation, 2019, 25(11):2113-2123.
Reviewer: Prof.
Erlie Jiang Typesetting: Quinta pokes "read the original text" , we progress togetherUpdated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy[J].
Biology of Blood and Marrow Transplantation, 2019, 25(11):2113-2123.
Reviewer: Prof.
Erlie Jiang Typesetting: Quinta pokes "read the original text" , we progress together