Causal inference for time-to-event data with a cured subpopulation.

When studying the treatment effect on time-to-event outcomes, it is common that some individuals never experience failure events, which suggests that they have been cured. However, the cure status may not be observed due to censoring which makes it challenging to define treatment effects. Current methods mainly focus on estimating model parameters in various cure models, ultimately leading to a lack of causal interpretations. To address this issue, we propose 2 causal estimands, the timewise risk difference and mean survival time difference, in the always-uncured based on principal stratification as a complement to the treatment effect on cure rates. These estimands allow us to study the treatment effects on failure times in the always-uncured subpopulation. We show the identifiability using a substitutional variable for the potential cure status under ignorable treatment assignment mechanism, these 2 estimands are identifiable. We also provide estimation methods using mixture cure models. We applied our approach to an observational study that compared the leukemia-free survival rates of different transplantation types to cure acute lymphoblastic leukemia. Our proposed approach yielded insightful results that can be used to inform future treatment decisions.

Frontline combination of dasatinib and low-intensity chemotherapy in adults with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia.

BACKGROUND: Studies on dasatinib-based low-intensity induction regimens and post-remission strategies are limited in China. Therefore, we conducted a single-center phase 2 trial in newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) to establish the efficacy and safety of this treatment approach. RESEARCH DESIGN AND METHODS: Patients received one month of dasatinib plus low-intensity chemotherapy and two months of dasatinib monotherapy for induction, followed by a single course of high-dose methotrexate for consolidation. Subsequently, they underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) or tyrosine kinase inhibitor (TKI)-based treatment for maintenance therapy between October 2015 and August 2022. RESULTS: Twenty-two patients were enrolled. Median age was 45 years (range, 20-71). The rates of major and complete molecular responses in the third month were 18.2% and 40.9% respectively. With a median follow-up of 15 months (range, 5-89), the estimated 3-year disease-free survival (DFS) and overall survival (OS) were 52.4% and 73.2%, respectively. The TKI-based cohort had a significantly poorer DFS (p = 0.014) and OS (p = 0.008) than the allo-HSCT cohort. CONCLUSIONS: Our results suggest that dasatinib-based low-intensity chemotherapy is safe and effective as an induction strategy in the Chinese population. Allo-HSCT plays a crucial role in the long-term outcomes of patients with Ph+ ALL. CLINICAL TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as NCT02690922.

Benefits and risks of clofarabine in adult acute lymphoblastic leukemia investigated in depth by multi-state modeling.

BACKGROUND: We recently reported results of the prospective, open-label HOVON-100 trial in 334 adult patients with acute lymphoblastic leukemia (ALL) randomized to first-line treatment with or without clofarabine (CLO). No improvement of event-free survival (EFS) was observed, while a higher proportion of patients receiving CLO obtained minimal residual disease (MRD) negativity. AIM: In order to investigate the effects of CLO in more depth, two multi-state models were developed to identify why CLO did not show a long-term survival benefit despite more MRD-negativity. METHODS: The first model evaluated the effect of CLO on going off-protocol (not due to refractory disease/relapse, completion or death) as a proxy of severe treatment-related toxicity, while the second model evaluated the effect of CLO on obtaining MRD negativity. The subsequent impact of these intermediate events on death or relapsed/refractory disease was assessed in both models. RESULTS: Overall, patients receiving CLO went off-protocol more frequently than control patients (35/168 [21%] vs. 18/166 [11%], p = 0.019; HR 2.00 [1.13-3.52], p = 0.02), especially during maintenance (13/44 [30%] vs. 6/56 [11%]; HR 2.85 [95%CI 1.08-7.50], p = 0.035). Going off-protocol was, however, not associated with more relapse or death. Patients in the CLO arm showed a trend towards an increased rate of MRD-negativity compared with control patients (HR MRD-negativity: 1.35 [0.95-1.91], p = 0.10), which did not translate into a significant survival benefit. CONCLUSION: We conclude that the intermediate states, i.e., going off-protocol and MRD-negativity, were affected by adding CLO, but these transitions were not associated with subsequent survival estimates, suggesting relatively modest antileukemic activity in ALL.

Increased donor inhibitory KIR are associated with reduced GVHD and improved survival following HLA-matched unrelated donor HCT in paediatric acute leukaemia.

Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after haematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity in the adult transplant setting. Paediatric acute leukaemia patients were retrospectively analysed, and KIR-KIRL combinations and maximal inhibitory KIR ligand (IM-KIR) scores were determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints. The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints remained significant for relevant downstream events. KIR-KIRL combinations were significantly predictive for reduced grade 3-4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM-KIR = 5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse-free survival, GRFS and overall survival. This study demonstrates that NK cell KIR HLA interactions may be relevant to the paediatric acute leukaemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in paediatric recipients with acute leukaemia to optimize clinical outcomes.

First complete remission favours haploidentical haematopoietic stem cell transplantation with post-transplant cyclophosphamide over cord blood transplantation in acute lymphoblastic leukaemia.

To assess the benefits of HLA-haploidentical haematopoietic stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo) relative to those of umbilical cord blood (UCB) transplantation in acute lymphoblastic leukaemia (ALL), we analysed 1999 patients (PTCy-haplo, 330; UCB, 1669), using the nationwide Japanese registry. PTCy-haplo was associated with a significantly higher relapse rate, but lower non-relapse mortality, which results in overall survival and disease-free survival, comparable to those of UCB. Among patients in CR1, PTCy-haplo showed a significantly higher survival than UCB regardless of the CD34+ cell dose. Our findings provide valuable insights into the donor selection algorithm in allogeneic HSCT for adult patients with ALL.

Patterns and prognostic impact of CNS infiltration in adults with newly diagnosed acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is highly associated with central nervous system (CNS) infiltration and can be associated with higher risk of relapse. Conventional cytology (CC) is the traditional method for diagnosing CNS infiltration, although the use of immunophenotyping by flow cytometry (FC) has gained prominence in recent years due to its higher sensitivity. Also, some authors have proposed that CSF contamination by a traumatic lumbar puncture (TLP) could have a clinical impact. This retrospective study accessed the impact of CNS infiltration by CC or FC on overall survival, event-free survival, and relapse rate. In a cohort of 105 newly diagnosed ALL patients, CNS1, CNS2, and CNS3 status were found in 84%, 14%, and 2%, respectively. We found that extramedullary disease at the diagnosis, higher leukocyte counts, and higher blast percentage were associated with a positive CC. Sensitivity and specificity of CC were 53% and 98%, respectively. Three-year overall survival was 42.5%. Conversely, TLP was not associated with a positive CC nor had an impact on relapse rates. In multivariate analysis, a positive CC was associated with an increased relapse rate (HR 2.074, p = 0.037), while its detection by FC did not associate with this endpoint. Survival rates seem to be increasing over the last years by the adoption of a stratified CNS prophylaxis risk strategy. CSF contamination does not represent a major concern according to our report, as it did not increase CNS involvement or relapse rates.

SOHO State of the Art Updates and Next Questions: Update on the Approach to Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

The outcome of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) has improved significantly following the introduction of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). The addition of newer-generation and more potent TKIs resulted in higher rates of molecular responses and better survival. Achieving a complete molecular remission (CMR; disappearance of the BCR::ABL1 transcripts) within the first 3 months of therapy is an important endpoint in newly diagnosed Ph-positive ALL that identifies patients who have an excellent long-term survival and who may not need to receive an allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). Chemotherapy-free combinations with blinatumomab plus TKIs showed encouraging results with estimated 2 to 4 year overall survival (OS) rates of 80% to 90%. Treatment with blinatumomab and ponatinib resulted in a CMR rate of 84%, a 2-year event-free survival (EFS) of 78%, and a 2-year OS rate of 90%; only 1 patient underwent HSCT. The detection of measurable residual disease (MRD) is the most important factor predicting for disease relapse. Studies have shown that the next-generation sequencing (NGS) assay is more sensitive than RT-PCR for the detection of MRD in Ph-positive ALL. Approximately 15% to 30% of patients who achieve NGS MRD negativity at a sensitivity of 1 × 10-6 may still have detectable BCR::ABL1 transcripts by RT-PCR. Achieving NGS MRD negativity can also identify patients who may have durable remissions with a low risk of relapse. Herein, we discuss the current approach to the management of adults with Ph-positive ALL, the role of HSCT, MRD monitoring, and future therapies.

The burden of acute lymphoid leukemia among adolescents and young adults in the Western Pacific Region: evidence from Global Burden Disease 2019.

PURPOSE: Acute lymphoblastic leukemia (ALL) is a type of blood cancer that affects white blood cells. Here, we use data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, to estimate the burden and incidence rate changes in adolescents and young adults (AYA) ALL in the Western Pacific Region and to reveal potential risk factors of incidence- and mortality rates. METHODS: The GBD 2019 study data was stratified by sex, age, country, and territory. We calculated the Estimated annual percentage changes (estimated APC) in mortality and incidence rates for each of the 25 countries and territories of the western Pacific region from 1990 to 2019. RESULTS: This study found global AYA ALL incidence rates had increased while the mortality rates had decreased between 1990 and 2019. Moreover, healthcare access and quality (HAQ), and government per capita health spending were identified as country-level risk factors of AYA ALL incidence rates, while HAQ, male education, and sex were identified as mortality rate predictors in 25 Western Pacific Region countries. CONCLUSION: To address and reduce the burden of incidence and mortality among AYA, various regions around the world, particularly developing countries, could revise their AYA prevention and treatment strategies.

How I treat long-term survivors of childhood acute leukemia.

ABSTRACT: The population of survivors of childhood leukemia who reach adulthood is growing due to improved therapy. However, survivors are at risk of long-term complications. Comprehensive follow-up programs play a key role in childhood leukemia survivor care. The major determinant of long-term complications is the therapeutic burden accumulated over time. Relapse chemotherapy, central nervous system irradiation, hematopoietic stem cell transplantation, and total body irradiation are associated with greater risk of long-term complications. Other parameters include clinical characteristics such as age and sex as well as environmental, genetic, and socioeconomic factors, which can help stratify the risk of long-term complications and organize follow-up program. Early diagnosis improves the management of several late complications such as anthracycline-related cardiomyopathy, secondary cancers, metabolic syndrome, development defects, and infertility. Total body irradiation is the treatment associated with worse long-term toxicity profile with a wide range of complications. Patients treated with chemotherapy alone are at a lower risk of long-term complications, although the optimal long-term follow-up remains unclear. Novel immunotherapies and targeted therapy are generally associated with a better short-term safety profile but still require careful long-term toxicity monitoring. Advances in understanding genetic susceptibility to long-term complications could enable tailored therapeutic strategies for leukemia treatment and optimized follow-up programs.

Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children's Cancer Group study ALL-2015.

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).

Incidence and Mortality Rates for Childhood Acute Lymphoblastic Leukemia in Puerto Rican Hispanics, 2012-2016.

BACKGROUND: Acute lymphoblastic leukemia (ALL) accounts for 80% of all leukemias diagnosed in children. Although ALL age patterns are consistent across racial/ethnic groups, their incidence and mortality rates are highly variable. We assessed the age-standardized ALL incidence and mortality rates of Puerto Rican Hispanic (PRH) children and compared them with those of US mainland Hispanics (USH), non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and Non-Hispanic Asian or Pacific Islanders (NHAPI). METHODS: Differences between racial/ethnic groups were assessed by estimating the standardized rate ratio (SRR) for 2010 to 2014. Secondary data analyses of the Puerto Rico Central Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) databases were performed for the 2001 to 2016 period. RESULTS: PRH children had 31% lower incidence rates than USH, but 86% higher incidence rates than NHB. In addition, the incidence trends of ALL increased significantly from 2001 to 2016 among PRH and USH, with 5% and 0.9% per year, respectively. Moreover, PRH have a lower 5-year overall survival (81.7%) when compared with other racial/ethnic groups. CONCLUSIONS: PRH children were found to have disparities in ALL incidence and mortality rates compared with other racial/ethnic groups in the US. Additional research is warranted to identify the genetic and environmental risk factors that may be associated with the disparities observed. IMPACT: This is the first study reporting the incidence and mortality rates of childhood ALL for PRH and making comparisons with other racial/ethnic groups in the US. See related commentary by Mejía-Aranguré and Núñez-Enríquez, p. 999.

[Obesity and risk of relapse in patients with Acute Lymphoblastic Leukemia: A retrospective study]. / Obesidad y riesgo de recaídas en pacientes con Leucemia Linfoblástica Aguda: Estudio retrospectivo.

BACKGROUND: Obesity has been associated with a low-grade proinflammatory state, and it has been related to the development of cancer in general, including hematologic cancer. AIM: The present work aimed to identify the association of the diagnosis of obesity according to the body mass index (BMI) with prognostic factors of adult patients with Acute Lymphoblastic Leukemia (ALL). PATIENTS AND METHOD: This observational, retrospective study included hospitalized patients diagnosed with ALL of the B-cell lineages. BMI was estimated based on the weight and height registered on clinical records at the admission of the patients. The relapse risk and bone marrow relapse were determined, and the survival rate was measured. The statistical analysis included the Kaplan-Meier method using the log-Rank test. RESULTS: This study included 128 clinical records of patients. Weight had no significant association with relapse risk. The frequency of bone marrow relapse was 43.8%. Obesity did not impact overall survival (p = 0.640) or disease-free survival (p = 0.527). The presence of obesity does not behave as a relapse risk variable (p = 0.873). BMI with a 30 kg/m2 cut-off point did not influence relapse risk (OR 1.078). CONCLUSION: Obesity is not an independent risk factor for the prognosis of adult patients with Acute Lymphoblastic Leukemia B-lineage.

Progress in Transplants for Acute Lymphoblastic Leukemia.

Hematopoietic cell transplants are used to treat some adults with acute lymphoblastic leukemia, especially those with high-risk features, such as those with BCR::ABL1. This strategy may be changing given the safety and efficacy of modern tyrosine kinase inhibitors. Although these transplants are often successful, leukemia relapse remains the dominant cause of transplant failure. There are several approaches to this problem discussed by the authors of a recent article in the journal. The good news is therapy of recurrent leukemia posttransplant seems increasingly successful and for diverse reasons, survival is increasing substantially. See related article by Bazarbachi et al., p. 1004.

HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning with very low-dose antithymocyte globulin for relapsed/refractory acute leukemia in pediatric patients: a single-institution retrospective analysis.

The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.

Barriers to Care and Outcomes of Pediatric Acute Lymphoblastic Leukemia Treatment in the Gaza Strip.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide. Although children in high-income countries enjoy survival rates of ~90%, children in countries with limited resources suffer from survival rates of <35%. No published data on pediatric cancer incidence, management, or outcomes in the Gaza Strip are available. METHODS: A retrospective cohort study was undertaken for pediatric (below 12 y of age) ALL diagnoses admitted to the only pediatric cancer ward in the Gaza Strip between 2010 and 2015. Outcomes included event-free survival (EFS) and overall survival (OS) calculated by Kaplan-Meier estimates. Events were defined as induction failure, relapse, and death. RESULTS: The 3-year EFS estimate was 80% (95% confidence interval [CI], 66%-89%). The EFS at 1 and 3 years for high-risk ALL was 55% (95% CI, 27%-76%) and 23% (95% CI, 4%-51%), respectively. The 3-year OS was 93% (95% CI, 82%-97%). The 3-year OS for high-risk ALL was 69% (95% CI, 30%-90%). All 84 (100%) patients required referral to an outside hospital for definitive ALL diagnoses and induction therapy. Forty-four (52%) patients required at least one additional referral. CONCLUSIONS: The overall outcomes demonstrated relatively high survival rates at 3 years which may be artificially elevated due to exclusion of adolescents, limited follow up, and deceased patient charts unavailable. Structural determinants of health in Gaza lead to limited diagnostic and treatment capabilities, limited access to advanced medical training, and reliance on out-of-territory transfers for care. These barriers impact the access to comprehensive pediatric care within the Gaza Strip.

Late mortality among survivors of childhood acute lymphoblastic leukemia diagnosed during 1971-2008 in Denmark, Finland, and Sweden: A population-based cohort study.

OBJECTIVE: Investigate all-cause and cause-specific late mortality after childhood acute lymphoblastic leukemia (ALL) in a population-based Nordic cohort. METHODS: From the cancer registries of Denmark, Finland, and Sweden, we identified 3765 five-year survivors of ALL, diagnosed before age 20 during 1971-2008. For each survivor, up to five matched comparison subjects were randomly selected from the general population (n = 18,323). Causes of death were classified as relapse related, health related, and external. Late mortality was evaluated by cumulative incidences of death from 5-year survival date. Mortality hazard ratios (HR) were evaluated with Cox proportional models. RESULTS: Among the survivors, 315 deaths occurred during a median follow-up of 16 years from 5-year survival date (range 0-42). The majority were attributable to relapse (n = 224), followed by second neoplasm (n = 45). Cumulative incidence of all-cause late mortality at 15 years from diagnosis decreased gradually over treatment decades, from 14.4% (95% confidence interval [CI]: 11.6-17.2) for survivors diagnosed during 1971-1981, to 2.5% (95% CI: 1.3-3.7) for those diagnosed during 2002-2008. This was mainly attributable to a reduction in relapse-related deaths decreasing from 13.4% (95% CI: 10.7-16.1) for survivors diagnosed during 1971-1981 to 1.9% (95% CI: 0.9-2.8) for those diagnosed during 2002-2008. Health-related late mortality was low and did not change substantially across treatment decades. Compared to comparison subjects, all-cause mortality HR was 40 (95% CI: 26-61) 5-9 years from diagnosis, and 4.4 (95% CI: 3.4-5.6) ≥10 years from diagnosis. CONCLUSIONS: Survivors of ALL have higher late mortality than population comparison subjects. Among the survivors, there was a temporal reduction in risk of death from relapse, without increments in health-related death.

Prevalence of non-adherence and non-compliance during maintenance therapy in adults with acute lymphoblastic leukemia and their associations with survival.

OBJECTIVES: Explore patient adherence and physician compliance to protocol guidelines during maintenance therapy, including the association with survival in adults with acute lymphoblastic leukemia (ALL). METHODS: Blood counts, aminotransferase levels and prescribed 6-mercaptopurine (6MP)/methotrexate (MTX) doses were compared with the protocol guidelines to assess compliance. Non-adherence to the prescribed medication was confirmed in patients with unmeasurable 6MP metabolite levels and suspected in patients with low 6MP metabolites concurrent with aminotransferase and white blood cell count within normal ranges, while potential intermittent non-adherence was defined by >1.9 fold fluctuating 6MP metabolites. RESULTS: Physicians' non-compliance with insufficient dose increments of 6MP/MTX despite white blood cell counts above the target level comprised a median of 20.1% (interquartile range 9.7-39.3%) of the observed time in maintenance therapy, yet no association to relapse was found (P = .17). Non-adherence to 6MP was confirmed in 9.8% (5 of 51 patients), suspected in an additional 9.8% (5 of 51 patients), and intermittent non-adherence was suspected in 52.6% (20 of 38 patients). CONCLUSION: Although no association between non-compliance and leukemic relapse was found, likely due to lack of power, increased attention to this phase of ALL therapy is indicated.

Response to blinatumomab or inotuzumab ozogamicin for isolated extramedullary relapse of adult acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation: a case study.

Isolated extramedullary relapse (EMR) without bone marrow relapse (BMR) after allogeneic hematopoietic cell transplantation (allo-HCT) is a rare condition in patients with acute lymphoblastic leukemia (ALL), and the role of immunotherapeutic agents for these patients remains unclear. We analyzed treatment outcomes of blinatumomab or inotuzumab ozogamicin (INO) as first- or second-line salvage therapy in nine patients with Philadelphia chromosome-negative B-cell precursor ALL presenting with isolated EMR after previous allo-HCT. In seven patients receiving blinatumomab as first-line salvage therapy, 4 (57.1%) achieved complete remission (CR). Among the three patients without remission after blinatumomab, two switched to INO and subsequently showed responses {one CR and one partial response [PR]}, and one switched to multiagent chemotherapy that led to CR. In the two patients receiving first-line salvage therapy with INO, one showed PR and the other achieved CR. Overall, 6 (66.7%) of nine patients achieved CR, and five of them proceeded to allo-HCT in CR. The median overall survival after relapse was 27.8 months. In conclusion, both blinatumomab and INO showed good response rates and a safe bridging role to second allo-HCT in patients with isolated EMR. However, clinical differences between isolated EMR and EMR with BMR remain to be elucidated.

A case series of patients treated with inotuzumab ozogamicin for acute lymphoblastic leukemia relapsed after allogeneic hematopoietic cell transplantation.

This single-center retrospective study was performed in consecutive patients with acute lymphoblastic leukemia who relapsed after allogeneic hematopoietic cell transplantation (HCT) and received salvage therapy using inotuzumab ozogamicin (InO). Ten patients (median age: 27 years) treated between June 2018 and July 2020 who met the eligibility criteria were included in this study. Nine patients received InO in one cycle and seven of these patients achieved complete hematological remission after salvage chemotherapy including InO. Negative minimal residual disease was confirmed in all four evaluable patients. Eight patients were successfully bridged to the subsequent HCT. After HCT, veno-occlusive disease (VOD) developed in three patients, and caused the death of one. No patient received maintenance therapy. At present, five patients are disease-free and alive, and the overall and progression-free survival rates at 1 year were 60% and 40%, respectively. High rates of disease remission and bridging to HCT with comprehensive treatments including InO may have contributed to favorable outcomes. However, further investigation is needed to reduce post-HCT complications including VOD.