Effect of peptide-binding motif on survival of HLA-haploidentical transplantation with post-transplant cyclophosphamide.

Peptide-binding motif (PBM) model, a hierarchical clustering of HLA class I based on their binding specificity, was developed to predict immunopeptidome divergence. The effect of PBM mismatches on outcomes is unknown in HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo). We therefore conducted a retrospective study using national registry data in PTCy-haplo. Overall, 1352 patients were included in the study. PBM-A bidirectional mismatch was associated with an increased risk of overall mortality in multivariable analysis (hazard ratio, 1.26; 95% confidence interval, 1.06 to 1.50; p = 0.010). None of relapse, non-relapse mortality (NRM) and graft-versus-host disease showed significant differences according to PBM-A bidirectional mismatch status in the entire cohort. The impact of PBM-A bidirectional mismatch on overall survival (OS) was preserved within the HLA-A genotype bidirectional mismatch population, and their lower OS stemmed from higher relapse rate in this population. The worse OS due to high NRM with PBM-A bidirectional mismatch was prominent in lymphoid malignancies receiving reduced-intensity conditioning. The PBM model may predict outcomes more accurately than HLA genotype mismatches. In conclusion, this study demonstrated that the presence of PBM-A bidirectional mismatch elevated the risk of mortality of PTCy-haplo. Avoiding PBM-A bidirectional mismatch might achieve better outcomes in PTCy-haplo.

High-dose cytarabine plus gemtuzumab ozogamicin as consolidation therapy in patients with favorable- or intermediate-risk acute myeloid leukemia.

Previous prospective randomized trials have investigated the efficacy of gemtuzumab ozogamicin in the frontline treatment of acute myeloid leukemia (AML). We evaluated the efficacy of high-dose cytarabine with GO as consolidation therapy in 20 patients with favorable- or intermediate-risk AML in first complete remission. They included six patients with wild-type nucleophosmin (NPM1) core binding factor (CBF), ten with NPM1-mutated non-CBF, and four with wild-type NPM1 non-CBF. The median follow-up for the entire cohort was 62.0 months. The three-year overall survival (OS) and relapse-free survival (RFS) rates were 72.2% and 77.8%, respectively. OS and RFS were significantly higher for NPM1-mutated non-CBF AML than for wild-type NPM1 non-CBF AML (p = 0.001). We also examined the CD33 single-nucleotide polymorphism (SNP) rs12459419, which has been reported to influence the therapeutic efficacy of GO and CD33 expression. The CD33 expression ratio was higher in CD33 SNP C/C than in C/T (83.1% vs. 49.8%, p = 0.035), but 3-year OS and RFS did not differ significantly. These results suggest that consolidation therapy with high-dose cytarabine plus GO is highly effective in transplant-ineligible elderly patients and may be a reasonable treatment, especially for NPM1-mutated AML.

Treatment Outcomes in Patients with Conjunctival Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma.

Purpose: To report the outcomes of different therapies in patients with conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. Patients and Methods: This retrospective study included patients diagnosed with conjunctival MALT lymphoma between August 2000 and April 2022. Patients were classified into three groups according to their treatment: an observation group, a radiation therapy (RT) group, and a rituximab group (rituximab with or without chemotherapy). We analyzed overall survival (OS), overall, local, and systemic relapse-free survival (RFS), and adverse events after treatment. Results: This study included 15 patients (22 eyes). The 10-year OS was 100%. The 2-, 5-, and 10-year overall RFS rates were 80.1%, 41.2%, and 41.2% in all patients, respectively. The 2- and 5-year local RFS rates in the observation group were 100% and 0%, respectively. The 2-, 5-, and 10-year local RFS rates were 87%, 87%, and 87% in the RT group and 83%, 67%, and 67% in the rituximab group, respectively. The 2- and 5-year systemic RFS rates in the observation group were both 100%, and the 2-, 5-, and 10-year systemic RFS rates were 92%, 55%, and 55% in the RT group, and 100%, 60%, and 60% in the rituximab group, respectively. After RT, 53.3% of the eyes developed cataracts and 75% of these were treated with cataract surgery. In addition, 53.3% of the eyes developed dry eyes and were treated with eye drops. Rituximab with or without chemotherapy resulted in some systemic adverse events, but these improved following symptomatic therapies. Conclusion: RT resulted in good local control of conjunctival MALT lymphoma; however, systemic relapse may occur during long-term follow-up. Local and/or systemic relapse may also occur during long-term follow-up in patients treated by observation or rituximab with or without chemotherapy. Patients with conjunctival MALT lymphoma should be followed-up carefully for as long as possible after treatment.

CRISPR/Cas9 gene editing clarifies the role of CD33 SNP rs12459419 in gemtuzumab ozogamicin-mediated cytotoxicity.

The single-nucleotide polymorphism (SNP) rs12459419 is located at the intron/exon junction of CD33 exon2. When exon2 is skipped by this CD33 SNP, the full-length CD33 (CD33FL) is converted to a short CD33 isoform (CD33D2). Since gemtuzumab ozogamicin (GO) only recognizes CD33FL, the CD33 SNP may affect the clinical efficacy of GO. To elucidate the significance of CD33 SNP on GO reactivity, we leveraged the CRISPR/Cas9 genome-editing system to create OCI-AML3 cell lines with specifically modified CD33 SNPs. Levels of CD33 D2 mRNA were significantly higher in the T/T clone (p < 0.001), but CD33D2 protein was not detectable in any clones. There was no significant difference in CD33FL mRNA expression across edited clones, and CD33FL protein expression was lowest in T/T clones, followed by T/C and C/C. Cytotoxicity assays revealed that the IC50 of GO was significantly lower in T/C and C/C clones than in the T/T clone (p < 0.001). Our study demonstrated a difference in GO-induced cytotoxicity in CD33 SNP-edited clones, clearly indicating that at least one CD33 SNP allele, rs12459419 C, is important for sensitivity to GO.

[Successful induction therapy for acute myeloid leukemia under management with extracorporeal membrane oxygenation].

A 53-year-old woman presented with shortness of breath and hyperleukocytosis and was admitted to our hospital. Shortly after, she went into cardiopulmonary arrest and was resuscitated. Her white blood cell count was 566,000/µl, with 94.5% cup-like blasts positive for MPO staining and FLT3-ITD positive, so she was diagnosed with acute myeloid leukemia (AML) M1. She also had disseminated intravascular coagulation and tumor lysis syndrome. Extracorporeal membrane oxygenation (ECMO) was started to manage bilateral pulmonary thromboembolism that had developed due to deep vein thrombosis, and induction therapy was performed under ECMO. On the third day of illness, the patient developed cerebral hemorrhage. Hematological remission was confirmed on the 39th day of illness. After consolidation therapy with chemotherapy and an FLT3 inhibitor, she underwent allogeneic hematopoietic stem cell transplantation, and remains alive. Case reports suggest strong evidence of mortality benefit from ECMO in patients with hematologic malignancies, particularly when ECMO served as a bridge through chemotherapy. Our patient suffered from cardiopulmonary arrest due to hyperleukocytosis and pulmonary thromboembolism, but was saved by induction of remission under ECMO. Improvements in supportive care should lead to reduction in early deaths during induction therapy.

Hepatic arterial infusion of autologous CD34+ cells for hepatitis C virus-related decompensated cirrhosis: A multicenter, open-label, exploratory randomized controlled trial.

Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G-CSF)-mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

[Successful immunosuppressive therapy in female hemophilia A developing inhibitor after perioperative administration of factor VIII products].

A 62-year-old woman was diagnosed as a hemophilia A carrier (factor VIII activity 35%) on preoperative examination of an ovarian tumor. A total of 35,600 units of recombinant factor VIII products was administered perioperatively. On postoperative day 95, a subcutaneous hematoma formed and immunosuppressive therapy with prednisolone was started based on an APTT of 66 seconds, factor VIII (FVIII) activity of 3%, and FVIII inhibitor of 1 BU/ml. During this treatment, the patient was hospitalized due to ankle joint bleeds and required hemostatic treatment, but the inhibitor disappeared and FVIII activity recovered to 30% after postoperative day 438 with cyclophosphamide. F8 analysis revealed the patient carried a heterozygosity of p.Arg391Cys, which has previously been categorized as cross-reacting material (CRM)-positive severe hemophilia A. No high-risk mutations for inhibitor development were found. We also report the results of a desmopressin acetate hydrate test administered to the patient to prepare for future treatment in case of hemorrhage, since high-dose FVIII administration may have been a factor in inhibitor development.

Prognostic factors in haploidentical transplantation with post-transplant cyclophosphamide for acute myeloid leukemia.

BACKGROUND AIMS: Haploidentical hematopoietic stem cell transplantation (haplo-HCT) is an appropriate option when an HLA-matched related or unrelated donor is not available. Haplo-HCT using post-transplant cyclophosphamide (PTCy) is being increasingly performed worldwide due to its effective suppression of GVHD and its safety. METHODS: We conducted a large nationwide cohort study to retrospectively analyze 366 patients with acute myeloid leukemia undergoing haplo-HCT with PTCy between 2010 and 2019 and to identify prognostic factors. RESULTS: A multivariate Cox analysis revealed that an older recipient age (≥60 years), a male donor to a male recipient, a cytomegalovirus IgG-negative donor to a cytomegalovirus IgG-positive recipient, a poor cytogenetic risk, a noncomplete remission status at the time of transplantation, and a history of HCT were independently associated with worse overall survival (OS). Based on each hazard ratio, these factors were scored (1-2 points) and stratified by their total score into three groups: favorable (0-1 points), intermediate (2-3 points), and poor (4 points or more) groups, and 2-year OS rates were 79.9%, 49.2%, and 25.1%, respectively (P < 0.001). CONCLUSIONS: The present study revealed significant prognostic factors in haplo-HCT with PTCy, and a scoring system based on these factors may be used to predict outcomes.

Autologous HSCT with novel agent-based induction and consolidation followed by lenalidomide maintenance for untreated multiple myeloma.

Triplet regimen comprising proteasome inhibitors, immunomodulatory drugs, and dexamethasone (DEX) is a recommended induction/consolidation therapy for multiple myeloma (MM) patients eligible for transplant. In this Japanese phase II study conducted from 2017 to 2019, newly diagnosed MM patients aged 20-65 received four induction cycles with bortezomib (Bor), lenalidomide (Len), and DEX (VRD), followed by Bor and high-dose melphalan with autologous stem cell rescue. Subsequently, they underwent four consolidation cycles with carfilzomib, Len, and DEX (KRD), followed by Len maintenance until disease progression. A total of 141 patients were analyzed. In an intent-to-treat population, the complete or better response post induction was 19.9%, rising to 39.7%, 58.9%, and 62.4% after transplant, consolidation, and 1-year maintenance, respectively. With a median follow-up of 38 months, the 3-year progression-free survival (PFS) rate was 83.5% and the 3-year overall survival rate was 92.5%. Severe adverse events (≥grade 3) occurred in ~30% of patients; however, there was no treatment-related mortality. These findings clearly showed the tolerability and effectiveness of this protocol. Nevertheless, patients with high-risk cytogenetics showed a trend toward lower 3-year PFS than those without (77.8% vs. 89.4%, p = 0.051), and ultra-high-risk cytogenetics (≥2 high-risk cytogenetics) had an even worse prognosis, with 61.2% 3-year PFS. To overcome this situation, a more potent treatment strategy incorporating novel agents such as the CD38-antibody should be assessed in future studies.

Correlation of ex vivo and in vivo ammonia production with L-asparaginase biological activity in adults with lymphoid malignancies.

Silent inactivation of L-asparaginase (L-Asp) represents rapid clearance of L-Asp by anti-L-Asp IgG antibodies without clinical symptoms. Measurement of L-Asp activity is the gold standard for diagnosis of silent inactivation, but this test is not commercially available in Japan as of 2023. We evaluated ex vivo and in vivo ammonia production in relation to L-Asp activity. Blood samples from ten adult patients treated with L-Asp were collected to measure ammonia levels and L-Asp activity before the first dose and 24 h after the last dose of L-Asp, during each cycle of treatment. Plasma ammonia levels were analyzed immediately and 1 h after incubation at room temperature, and ex vivo ammonia production was defined as the increase in ammonia concentration. Ex vivo ammonia production correlated with L-Asp activity (R2 = 0.741), and ammonia levels measured immediately after blood collection were moderately correlated with L-Asp activity (R2 = 0.709). One patient with extranodal NK/T-cell lymphoma showed an increase in ammonia levels during the first cycle, but no increase in ammonia levels or L-Asp activity after L-Asp administration during the second cycle. Both ex vivo and in vivo ammonia production and surrogate markers are used for L-Asp biological activity.

Peripheral blood stem cell transplantation using HLA-haploidentical donor with post-transplant cyclophosphamide versus HLA-matched sibling donor for lymphoma.

Data comparing HLA-haploidentical donors and HLA-matched sibling donors (MSDs) in peripheral blood stem cell transplantation (PBSCT) for lymphoma are scarce. We retrospectively analyzed 465 patients with lymphoma aged 16 years or older who underwent PBSCT using haploidentical donors with post-transplant cyclophosphamide (PTCy-haplo) (n = 166) or MSDs with calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis (n = 299). Two-year overall survival (OS), progression-free survival (PFS), and GVHD-free, relapse-free survival (GRFS) in the PTCy-haplo and MSD groups were 49.2% versus 51.9% (P = 0.64), 38.0% versus 39.9% (P = 0.97), and 27.7% versus 18.5% (P = 0.006), respectively. In multivariable analyses, PTCy-haplo recipients had slower neutrophil recovery (hazard ratio [HR], 0.62; P < 0.001) and platelet recovery (HR, 0.54; P < 0.001), lower risk of chronic GVHD (HR, 0.64; P = 0.038) and extensive chronic GVHD (HR, 0.45; P = 0.008), and better GRFS (HR, 0.66; P = 0.003) than MSD transplant recipients. OS, PFS, relapse or progression, and non-relapse mortality were similar between the groups. The difference might be mainly due to PTCy use rather than donor type; however, the results suggested that PTCy-haplo could be a possible option as an alternative to conventional MSD transplantation for lymphoma in PBSCT.

Outcomes of Cessation of Nucleos(t)ide Analog Administration on Hepatitis B Virus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Retrospective Study.

Monitoring of hepatitis B virus (HBV)-DNA and HBV-DNA-guided preemptive therapy using nucleos(t)ide analogs (NAs) are recommended to prevent the development of hepatitis due to HBV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recipients with resolved HBV infection. However, little is known about the appropriate duration of NA treatment and the effect of NA cessation on the recurrence of HBV reactivation. This study aimed to clarify the consequences of NA cessation in allo-HSCT recipients with resolved HBV infection who experienced HBV reactivation following transplantation. We retrospectively reviewed the clinical records of recipients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative, anti-HBc-positive) before allo-HSCT who had been diagnosed with HBV reactivation (HBsAg-positive and/or HBV-DNA detectable) after allo-HSCT between January 2010 and December 2020. A total of 72 patients from 16 institutions were registered (median age, 60 years; age range, 27 to 73 years; 42 males and 30 females). The day of initial HBV reactivation ranged from day 10 to day 3034 after allo-HSCT (median, 513 days). Anti-HBs were lost in >80% of the patients at the time of HBV reactivation. All 72 patients received preemptive NAs, and no fatal HBV reactivation-related hepatitis was observed. HBV-DNA without hepatitis was continuously detected in 5 patients during the follow-up period. Administration of NAs was discontinued in 24 of 72 patients (33%) by physician decision. Second HBV reactivation occurred in 11 of the 24 patients (46%) in whom administration of NAs was discontinued. The duration of NA treatment did not differ significantly between patients with or without second HBV reactivation. The frequency of further HBV reactivation tended to be lower in patients with an anti-HBs titer of >10 mIU/mL at the time of NA cessation. Multiple reactivations of HBV after NA cessation was common in patients with HBV reactivation who underwent allo-HSCT despite the long duration of NAs. Careful monitoring of HBV-DNA is important even after the discontinuation of NAs in the case with HBV reactivation after allo-HSCT, because multiple reactivations could occur. Active immunization by HB vaccine might be effective for suppressing further HBV reactivation after cessation of NAs.

Prognostic impact of HLA supertype mismatch in single-unit cord blood transplantation.

The "human leukocyte antigen (HLA) supertype" is a functional classification of HLA alleles, which was defined by structural features and peptide specificities, and has been reportedly associated with the clinical outcomes of viral infections and autoimmune diseases. Although the disparity in each HLA locus was reported to have no clinical significance in single-unit cord blood transplantation (sCBT), the clinical significance of the HLA supertype in sCBT remains unknown. Therefore, we retrospectively analyzed clinical data of 1603 patients who received sCBT in eight institutes in Japan between 2000 and 2017. Each HLA allele was categorized into 19 supertypes, and the prognostic effect of disparities was then assessed. An HLA-B supertype mismatch was identified as a poor prognostic factor (PFS: hazard ratio [HR] = 1.23, p = 0.00044) and was associated with a higher cumulative incidence (CI) of relapse (HR = 1.24, p = 0.013). However, an HLA-B supertype mismatch was not associated with the CI of acute and chronic graft-versus-host-disease. The multivariate analysis for relapse and PFS showed the significance of an HLA-B supertype mismatch independent of allelic mismatches, and other previously reported prognostic factors. HLA-B supertype-matched grafts should be selected in sCBT.

Effect of graft-versus-host disease on outcomes of HLA-haploidentical peripheral blood transplantation using post-transplant cyclophophamide.

There is limited evidence regarding the association between graft-versus-host disease (GVHD) and reduced relapse in patients who undergo allogeneic hematopoietic stem cell transplantation from haploidentical donors (haplo-HSCT) using post-transplant cyclophosphamide (PTCY). We investigated the association between GVHD and transplant outcomes in 938 patients who received haplo-HSCT using PTCY. Overall survival (OS), relapse rate, and non-relapse mortality (NRM) were evaluated using landmark analysis at the landmark points at 100 and 360 days after HSCT for acute and chronic GVHD, respectively. Grade I-II acute GVHD was not associated with OS (adjusted hazard ratio: 1.15, 95% confidence interval: 0.85-1.57), relapse (1.03, 0.74-1.45) and NRM (1.15, 0.74-1.77). Conversely, grade III-IV acute GVHD was associated with higher NRM (3.16, 1.61-6.19), but no other outcomes. Limited chronic GVHD was not associated with OS (1.11, 0.48-1.95), relapse (1.05, 0.30-3.75) and NRM (1.30, 0.45-3.79). Extensive chronic GVHD was associated with higher NRM (2.40, 1.03-5.57), but no other outcome. In conclusion, any GVHD was not associated with a reduced relapse rate and improved OS, and Grade III-IV acute GVHD and extensive chronic GVHD were associated with higher NRM in patients who received haplo-HSCT using PTCY.

Low- versus standard-dose post-transplant cyclophosphamide as GVHD prophylaxis for haploidentical transplantation.

Haploidentical haematopoietic cell transplantation (haplo-HCT) using post-transplant cyclophosphamide (PTCY) as graft-versus-host disease (GVHD) prophylaxis is the standard of care for various haematological malignancies. The original PTCY dose after haplo-HCT was 100 mg/kg, but no dose-finding studies have been performed to identify the optimal dose. We performed a retrospective analysis to compare standard-dose PTCY (100 mg/kg) with reduced-dose PTCY (80 mg/kg): 969 in the standard-dose group and 538 in the reduced-dose group. As there was a significant difference between the two groups regarding patient and transplant characteristics, we performed propensity score (PS) matching. After PS matching, 425 patients in each group were included. The probabilities of 2-year OS were 55.9% in the standard-dose group and 47.0% in the reduced-dose group (p = 0.36). The cumulative incidences of 2-year non-relapse mortality were 21.3% in the standard-dose group and 20.5% in the reduced-dose group (p = 0.55). There was no significant difference in the incidence of acute (grade II-IV 29.2% [95% CI, 24.9-33.6] vs. 25.3% [95% CI, 21.3-29.6]; grade III-IV 7.3% [95% CI, 5.1-10.0] vs. 6.6% [95% CI, 4.5-9.3]) or chronic GVHD. In conclusion, reduced- and standard-dose PTCY were comparable in terms of major clinical outcomes.

Impact of a third dose of anti-SARS-CoV-2 vaccine in hematopoietic cell transplant recipients: A Japanese multicenter observational study.

This prospective observational study aimed to assess the serological response and safety after the third booster shot of SARS-CoV-2 mRNA vaccines in 292 hematopoietic cell transplant (HCT) recipients. In our patients, mild systemic reactions were present in 10-40% and GVHD aggravation in 1.1%. Overall, clinically relevant response (>250 U/mL) was observed in 93.1% of allogeneic (allo)-HCT recipients and 70.6% of autologous (auto)-HCT recipients, respectively. Of note, detectable antibody response with any titer following the first two doses was a powerful predictor for adequate response after booster shot in both cohorts. For such patients, 98.8% of allo- and 92.3% of auto-HCT recipients obtained clinically relevant response after dose 3. In addition, continued systemic steroid and/or calcineurin inhibitors at the booster shot significantly correlated with serological response. These findings highlighted that booster vaccination efficiently improved serological response without safety concerns and thus recommended for the majority of HCT recipients.

[Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in the first complete remission].

The treatment outcomes for adult Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) have improved with the introduction of pediatric protocols. On assessing long-term survivors of chemotherapy who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), it was found that these patients had good performance status and few complications. Therefore, in the first complete remission (1CR) of ALL, allo-HSCT is indicated for patients in whom the results of chemotherapy are predicted to be poor. In adolescent and young adult (AYA) patients with ALL, allo-HSCT is recommended in the 1CR if end of consolidation measurable residual disease (MRD) is positive. In adults with ALL (non-AYA patients), if end of induction MRD is negative, chemotherapy should be continued and allo-HSCT is not recommended. In the future, it is necessary to perform a comprehensive evaluation of individual patients that considers MRD, as well as the initial tumor burden and biological features of leukemic cells.

Changing trends in the risk factors for second primary malignancies after autologous stem cell transplantation for multiple myeloma before and after the introduction of proteasome inhibitors and immunomodulatory drugs.

The incidence of second primary malignancies (SPM) in long-term survivors of multiple myeloma (MM) is increasing because of increased life expectancy. We retrospectively analyzed the risk factors for SPM in patients with MM after autologous stem cell transplantation (ASCT) before and after the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs). In total, 2,340 patients newly diagnosed with MM who underwent ASCT between 1995 and 2016 were enrolled in this study. Forty-three patients developed SPM (29 solid, 12 hematological, and 2 unknown tumors), with cumulative incidence rates of 0.8% and 2.5% at 24 and 60 months, respectively. The cumulative incidence rates of hematological and solid SPM at 60 months were 0.8% and 1.8%, respectively. The overall survival (OS) rate at 60 months after ASCT was 62.9% and the OS rates after the diagnosis of SPM at 24 months were 72.2% for hematological SPM and 70.9% for solid SPM. Multivariate analysis revealed that the use of IMiDs (P=0.024) and radiation (P=0.002) were significant independent risk factors for SPM. The probabilities of developing SPM and death due to other causes (mainly MM) at 60 months were 2.5% and 36.5%, respectively, indicating that the risk of SPM was lower than that of death from MM. Furthermore, SPM between the pre-novel and novel agent eras (ASCT between 2007 and 2016) groups significantly increased (1.9% vs. 4.3% at 60 months; P=0.022). The early occurrence of SPM after ASCT should be monitored cautiously.

Cardiovascular adverse events and prognosis in patients with haematologic malignancies and breast cancer receiving anticancer agents: Kurume-CREO Registry insights.

AIMS: Cancer treatment-related cardiovascular toxicity (CTR-CVT) is a growing concern in patients undergoing anticancer therapy. The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) risk assessment tools have been proposed for the baseline cardiovascular (CV) risk stratification of patients with cancer. This study investigated the incidence of CV adverse events in clinical practice, also using the HFA-ICOS risk tool. METHODS AND RESULTS: This single-centre, prospective, observational study was conducted at Kurume University Hospital from October 2016 to August 2021, including patients aged ≥20 years with haematologic malignancies or breast cancer who were receiving anticancer agents. Cardiovascular assessments were performed at enrolment and every 6 months until August 2021, with additional assessments for suspected CV adverse events. The primary endpoint was common terminology criteria for adverse events v4.0 Grade ≥2, and the secondary endpoints were all-cause and CV deaths. Of the enrolled 486 patients, CV adverse events occurred in 24.5, 15.8, 38.1, and 18.0% of patients with leukaemia, malignant lymphoma, multiple myeloma, and breast cancer, respectively. Patients at high or very high risk had a significantly higher incidence of CV events, according to the HFA-ICOS risk tool. Cardiovascular death occurred in 4 (0.8%) patients during follow-up. CONCLUSION: This study revealed that 16-38% of patients with haematologic malignancies and breast cancer developed CTR-CVT during follow-up, in which patients with high/very high risk were well predicted by the HFA-ICOS risk assessment tool. Monitoring and managing CV risk factors are essential for safe cancer therapy.

As the elderly population grows worldwide, cancer and cardiac diseases have become the leading causes of death in many countries, including Japan. With advances in cancer treatment, survival rates have improved, resulting in an increasing number of cancer survivors developing therapy-related cardiovascular (CV) problems. The study, conducted at Kurume University Hospital, examined 486 participants with haematologic malignancies and breast cancer. The result demonstrates CV adverse events in 12, 45, 24, and 16 patients with leukaemia, malignant lymphoma, multiple myeloma, and breast cancer, respectively. Heart failure and left ventricular systolic dysfunction were the most common adverse events. This study demonstrates the importance of monitoring patients with cancer for potential CV risks and highlights the need for further research to improve treatment protocols for those at higher risk. Key findings include This prospective study conducted in Japan revealed a high incidence of adverse cardiovascular (CV) events in patients with haematologic malignancies and breast cancer treated with anticancer agents but a low CV mortality rate during the mid-term follow-up period. Patients at high/very high risk, as determined by the Heart Failure Association-International Cardio-Oncology Society risk assessment tool, experienced a higher incidence of CV events and heart failure compared with those at low and moderate risks.