BACKGROUND: The role of autologous hematopoietic stem cell transplantation (AHSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL) remains controversial. The aim of this retrospective study was to analyze results of AHSCT and to identify prognostic factors. METHODS: Overall, 700 patients transplanted in first complete remission between the years 1999-2020 were included. Median patient age was 31.9 years (68% male). B-cell precursor ALL (BCP-ALL) and T-cell precursor ALL (TCP-ALL) was diagnosed in 35% and 65%, respectively. Among 190 patients with available data, negative minimal residual disease (MRD) status was reported in 167 (88%) cases. RESULTS: The probabilities of overall survival (OS) and leukemia-free survival (LFS) at 2 years were 67% and 56%; relapse incidence (RI) and non-relapse mortality (NRM) were 39% and 5%, respectively. TCP-ALL was associated with lower RI (41% vs. 56%, p=0.001), higher LFS (52% vs. 38%, p=0.002) and OS (58% vs 45%, p=0.001) at 5 years when compared to BCP-ALL. In the multivariate analysis, TCP-ALL and longer interval from diagnosis do AHSCT were associated with reduced risk of relapse (HR 0.7, p=0.006 and HR=0.95, p=0.018), better LFS (HR=0.76, p=0.02 and HR=0.95, p=0.01) and OS (HR=0.75, p=0.024 and HR=0.94, p=0.013, respectively). Increasing patient age was associated with higher NRM (HR=1.49, p<0.0001), worse LFS (HR=1.1, p=0.01) and OS (HR=1.17, p=0.0001). CONCLUSIONS: Autologous hematopoietic stem cell transplantation is relatively safe option of late treatment intensification in adults with Ph- ALL. It may be a valuable option especially in patients with TCP-ALL, however it should be proved in prospective clinical trials.

• Keywords
• Autologous stem cell transplantation, Complete remission, Philadelphia negative acute lymphoblastic leukemia,
• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * therapy   mortality   MeSH
• Transplantation, Autologous MeSH
• Adult MeSH
• Philadelphia Chromosome MeSH
• Remission Induction MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Neoplasm, Residual MeSH
• Hematopoietic Stem Cell Transplantation * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced intensity conditioning (RIC) is an option for elderly patients with acute lymphoblastic leukemia (ALL). We retrospectively compared results of RIC-allo-HCT from either a matched sibling donor (MSD, n = 209) or matched unrelated donor (MUD, n = 209) with autologous (auto, n = 142) HCT for patients aged 55 years or more treated in first complete remission (CR1) between 2000 and 2018. The probabilities of leukemia-free survival (LFS) at 5 years were 34% for RIC-allo-HCT versus 39% for auto-HCT (p = 0.11) while overall survival (OS) rates were 42% versus 45% (p = 0.23), respectively. The incidence of relapse (RI) and non-relapse mortality (NRM) was 41% versus 51% (p = 0.22) and 25% versus 10% (p = 0.001), respectively. In a multivariate model, using auto-HCT as reference, the risk of NRM was increased for MSD-HCT (Hazard ratio [HR] = 2.1, p = 0.02) and MUD-HCT (HR = 3.08, p < 0.001), which for MUD-HCT translated into a decreased chance of LFS (HR = 1.55, p = 0.01) and OS (HR = 1.62, p = 0.008). No significant associations were found with respect to the risk of relapse. We conclude that for patients with ALL in CR1, aged above 55 years, auto-HCT may be considered a transplant option alternative to RIC-allo-HCT, although its value requires verification in prospective trials.

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * therapy   MeSH
• Leukemia, Myeloid, Acute * therapy   MeSH
• Acute Disease MeSH
• Transplantation, Homologous methods   MeSH
• Bone Marrow MeSH
• Humans MeSH
• Graft vs Host Disease * etiology   MeSH
• Transplantation Conditioning methods   MeSH
• Prospective Studies MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Hematopoietic Stem Cell Transplantation * methods   MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

T-cell malignancies can be divided into precursor (T-acute lymphoblastic leukemia/lymphoblastic lymphoma, T-ALL/LBL) and mature T-cell neoplasms, which are comprised of 28 different entities. Most of these malignancies are aggressive with rather poor prognosis. Prognosis of relapsed/refractory (R/R) disease is especially dismal, with an expected survival only several months after progression. Targeted therapies, such as antiCD30 immunotoxin brentuximab vedotin, antiCD38 antibody daratumumab, and anti-CCR4 antibody mogamulizumab are effective only in subsets of patients with T-cell neoplasms. T-cells equipped with chimeric antigen receptor (CAR-Ts) are routinely used for treatment of R/R B-cell malignancies, however, there are specific obstacles for their use in T-cell leukemias and lymphomas which are fratricide killing, risk of transfection of malignant cells, and T-cell aplasia. The solution for these problems relies on target antigen selection, CRISPR/Cas9 or TALEN gene editing, posttranslational regulation of CAR-T surface antigen expression, and safety switches. Structural chromosomal changes and global changes in gene expression were observed with gene-edited products. We identified 49 studies of CAR-based therapies registered on www.clinicaltrials.gov. Most of them target CD30 or CD7 antigen. Results are available only for a minority of these studies. In general, clinical responses are above 50% but reported follow-up is very short. Specific toxicities of CAR-based therapies, namely cytokine release syndrome (CRS), seem to be connected with the antigen of interest and source of cells for manufacturing. CRS is more frequent in antiCD7 CAR-T cells than in antiCD30 cells, but it is mild in most patients. More severe CRS was observed after gene-edited allogeneic CAR-T cells. Immune effector cell associated neurotoxicity (ICANS) was mild and infrequent. Graft-versus-host disease (GvHD) after allogeneic CAR-T cells from previous hematopoietic stem cell donor was also observed. Most frequent toxicities, similarly to antiCD19 CAR-T cells, are cytopenias. CAR-based cellular therapy seems feasible and effective for T-cell malignancies, however, the optimal design of CAR-based products is still unknown and long-term follow-up is needed for evaluation of their true potential.

• Keywords
• CAR-T cells, T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma, T-cell lymphoma, chimeric antigen receptor (CAR), immunotherapy, therapy,
• Publication type
• Journal Article MeSH
• Review MeSH