Severe autoimmune hemolytic anemia following immunotherapy with checkpoint inhibitors in two patients with metastatic melanoma: a case report.

Introduction: Over the past decade, immune checkpoint inhibitors such as antibodies against cytotoxicity T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have become an important armamentarium against a broad spectrum of malignancies. However, these specific inhibitors can cause adverse autoimmune reactions by impairing self-tolerance. Hematologic side effects of immune checkpoint inhibitors, including autoimmune hemolytic anemia (AIHA), are rare but can be life-threatening. Case report: Herein, we report two patients on immune checkpoint inhibitors for metastatic melanoma who developed AIHA with symptoms of dyspnea and fatigue. In the first patient, symptoms alleviated after discontinuation of combined anti CTLA-4 and anti-PD-1 therapy, initiation of corticosteroids and application of a single red blood cell transfusion. Due to subsequent progress of melanoma, combinational anti-PD-1 and tyrosine kinase inhibitor therapy was initiated based on multidisciplinary tumor board decision. After two months, she again developed the described hematological and clinical signs of AIHA leading to cessation of anti-PD-1 therapy and initiation of corticosteroids, which again resulted in an alleviation of her symptoms. Due to further progression, the patient received dacarbazine for several months before she decided to stop any therapy other than palliative supportive care. In the second patient, discontinuation of anti-PD-1 therapy and initiation of corticosteroids entailed a complete alleviation of his symptoms. After refusing chemotherapy due to subsequent melanoma progression, he received radiotherapy of bone metastases and is currently enrolled in a clinical trial. The patient did not develop AIHA ever since. Conclusion: Hematologic immune-related adverse events due to treatment with immune checkpoint inhibitors are rare but can have life-threatening consequences. If dyspnea and other clinical symptoms are present, AIHA should be considered as a potential cause and treated promptly in a multidisciplinary setting. An expanded comprehension of risk factors and pathogenesis of AIHA is needed to identify high-risk patients beforehand, leading to more effective predictive and reactive treatment approaches.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Secondary bladder and colorectal cancer after treatments for prostate cancer: A population based study.

BACKGROUND: Prostate cancer (PCa) patients receiving radiotherapy may be predisposed to secondary malignancies. This study aimed to determine the association between PCa treatments, including radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT) and androgen deprivation therapy (ADT); and secondary bladder and colorectal cancer. METHODS: A cohort study was constructed using Quebec administrative databases (Med-Echo and RAMQ). Included men were diagnosed and treated for PCa between 2000 and 2016. Patients with bladder or colorectal cancer prior to PCa were excluded. Follow-up ended at the earliest of the following: incidence of bladder or colorectal cancer, death, or December 31, 2016. EBRT, BT, EBRT+ADT, RP + ADT or ADT only were compared individually to RP. The incidence of secondary bladder and colorectal cancer were computed. Inverse probability of treatment weighting (IPTW) based on a propensity score was used to control for potential confounding. IPTW-Cox proportional hazards models were used. RESULTS: A significant association was found between secondary bladder cancer and EBRT (HR: 1.84, 95%CI: 1.60;2.13), and also EBRT+ADT (HR: 2.08, 95%CI: 1.67;2.56), but not with BT (HR: 1.36, 95%CI: 0.68;2.74). Secondary colorectal cancer was significantly associated to either EBRT (HR: 1.36, 95%CI: 1.21;1.53); or BT (HR: 2.46, 95%CI: 1.71;3.54). The association between ADT alone and both secondary cancers was also significant (HR: 1.98, 95%CI: 1.69;2.31 and HR: 1.69, 95%CI: 1.49;1.92, respectively). CONCLUSIONS: Compared to PCa patients undergoing RP, the secondary bladder cancer was associated with EBRT, ADT, alone or in combination. The secondary colorectal cancer was also associated with receiving either EBRT, BT or ADT.

Second Malignant Neoplasms Following Treatment for Hepatoblastoma: An International Report and Review of the Literature.

Treatment intensification has improved survival in patients with hepatoblastoma (HB); however, these treatments are associated with an increased risk of late effects, including second malignant neoplasms (SMNs). Data is limited regarding SMNs following HB treatment. Cases of SMNs following treatment for HB reported in the literature and from personal communication were analyzed to further assess this late effect. Thirty-eight patients were identified. The median age at diagnosis of HB was 16 months (range: 3 to 168 mo). All patients had received a platinum agent, and almost all had anthracycline exposure. The SMNs reported were hematopoietic malignancies (n=19), solid tumors (n=12), and post-transplant lymphoproliferative disorder (n=7). Of the 36 patients with outcome data, 19 survived. SMNs following HB treatment were primarily seen in patients with chemotherapy exposure, a history of liver transplantation, hereditary tumor predisposition syndromes, and/or a history of radiation treatment. Hematopoietic malignancies were the most common SMN reported in this cohort and were diagnosed earlier than other SMNs. Prospective collection of data through a companion late effects study or international registry could be used to further evaluate the rates and risks of SMNs as well as tumor predisposition syndromes in patients treated for HB.

Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML.

Molecularly defined secondary acute myeloid leukemia is associated with a prior myeloid neoplasm and confers a worse prognosis. We compared outcomes of molecularly defined secondary AML patients (n = 395) treated with daunorubicin and cytarabine (7 + 3, n = 167), liposomal daunorubicin and cytarabine (CPX-351, n = 66) or hypomethylating agents (HMA) + venetoclax (VEN) (n = 162). Median overall survival (OS) was comparable between treatment groups among patients aged >60 years. In a multivariable model HMA + VEN vs. 7 + 3 was associated with better OS (hazard ratio [HR] 0.64 [95% confidence interval (CI) 0.42-0.98, p = 0.041]), whereas CPX-351 vs. 7 + 3 was not (HR 0.79 [CI 95% 0.50-1.25, p = 0.31]). Allogeneic hematopoietic stem cell transplantation, BCOR and IDH mutations were associated with improved OS; older age, prior myeloid disease, NRAS/KRAS mutations, EZH2 mutation, and monosomal karyotype were associated with worse OS. When analyzed in each treatment separately, the IDH co-mutations benefit was seen with 7 + 3 and the detrimental effect of NRAS/KRAS co-mutations with HMA + VEN and CPX-351. In pairwise comparisons adjusted for age, HMA + VEN was associated with improved OS vs. 7 + 3 in patients with SF3B1 mutation and improved OS vs. CPX-351 in those with RNA splicing factor mutations. In molecularly defined secondary AML treatment with HMA + VEN might be preferred but could further be guided by co-mutations.

FDA Adds Boxed Warning to CAR T-Cell Therapies, but Says Benefits Outweigh Risks of Secondary Cancers.

This Medical News article discusses the US Food and Drug Administration's new boxed warning requirement and investigation of secondary malignancies after CAR T-cell therapy.

Definitive single fraction spine stereotactic radiosurgery for metastatic sarcoma: Simultaneous integrated boost is associated with high tumor control and low vertebral fracture risk.

INTRODUCTION: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). RESULTS: 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7-27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5-32) and 52.7 cm3 (IQR 29.5-87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/ß = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7-18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7-25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8-25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782-0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). CONCLUSION: This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.

Short course radiotherapy versus radiochemotherapy for locally advanced rectal cancers in the elderly (UNICANCER PRODIGE 42/GERICO 12 study): Quality of life and comprehensive geriatric assessment.

BACKGROUND: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study. PATIENTS AND METHODS: In all, 101 patients ≥75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m2, 5 days/week) with delayed surgery (7 weeks ± 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA. RESULTS: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference. CONCLUSION: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged ≥75 treated for locally advanced rectal cancer.

Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study.

BACKGROUND: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. METHODS: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. RESULTS: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. DISCUSSION: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.

Second Malignancy Probabilities in Patients With Breast Cancer Treated With Conventional Versus Hypofractionated External Beam Radiation Therapy in the Adjuvant Setting.

AIMS: For women with breast cancer, seminal studies have shown that adjuvant hypofractionated external beam radiation therapy (hEBRT) maintains similar outcomes and may reduce overall costs compared with conventionally fractionated external beam radiation therapy (cEBRT). However, it is unclear whether hEBRT may be associated with differential risk of development of radiation-induced second malignancies compared with cEBRT. Because the occurrence of second malignancies is small, large databases may improve our understanding of the relative risk of second malignancies between hEBRT and cEBRT. MATERIALS AND METHODS: Using the National Cancer Database, we carried out a retrospective cohort analysis of women diagnosed with non-metastatic, stage 0-III breast cancer from 2004 to 2017. All patients had a lumpectomy or mastectomy and a follow-up time of at least 60 months after diagnosis. The probability of second malignancies in women receiving adjuvant cEBRT or hEBRT was compared using multivariable logistic regression adjusting for sociodemographic, geographical, clinical and treatment factors, allowing for relative (but not absolute) comparison of second malignancy risk. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up time were also conducted. RESULTS: Of the 125 228 women in our study, 115 576 (92.3%) received cEBRT and 9652 (7.71%) received hEBRT. The median age of the cohort was 60 (interquartile range 51-68) years at diagnosis and the median follow-up time was 99.61 (interquartile range 77.5-128.49) months. Upon adjusting for sociodemographic and clinical factors, patients who received hEBRT had no difference in relative risk than patients who received cEBRT (odds ratio 0.937, 95% confidence interval 0.869-1.010, P = 0.091). In analyses stratified by year of diagnosis, and stratified by length of follow-up, there was no difference in second malignancy probability between patients who completed hEBRT and patients who completed cEBRT. CONCLUSIONS: In this analysis of over 120 000 women with non-metastatic breast cancer, hEBRT was not associated with different odds of developing second malignancies compared with cEBRT. Our findings may inform patient counselling in the choice of radiation regimens for breast cancer and further support the safety of hypofractionated regimens for breast cancer.

Effectiveness and risk of second primary malignancies after radiotherapy in major salivary gland carcinomas: A retrospective study using SEER database.

OBJECTIVE: To investigate the effectiveness of radiotherapy and its association with second primary malignancies (SPMs) risk in major salivary gland carcinomas (MSGCs) patients. METHODS: Cohort 1 included 7274 surgically treated MSGC patients from the Surveillance, Epidemiology, and End Results database, assessing the effectiveness of radiotherapy. Cohort 2 (n = 4213) comprised patients with ≥5-year survival in Cohort 1 to study SPMs. RESULTS: Radiotherapy decreased overall survival in MSGCs patients, but improved it in high-grade MSGCs. Cumulative SPMs incidences at 25 years were 16.5% in the radiotherapy (RT) group compared to 14.5% in the non-radiotherapy (NRT) group. For second head and neck carcinomas (SHNCs), incidences were 3.4% in RT versus 1.6% in NRT. Radiotherapy increased the relative risks of tumors, particularly SHNCs (RR = 1.78). The 10-year OS rates of SHNCs after radiotherapy were significantly lower. CONCLUSION: Radiotherapy improves survival in advanced-stage MSGCs but increases the risk of developing SPMs, particularly SHNCs.

Lifetime risks of second primary malignancies after pediatric Hodgkin lymphoma and non-Hodgkin lymphoma.

OBJECTIVES: Survivors after pediatric Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are with lifetime risk for second primary malignancy (SPM). This necessitates a thorough analysis to better understand the potential long-term health implications for these individuals. METHODS: We used a US-wide population-based cancer registry data to quantify the SPM risk and identify its incidence patterns among pediatric lymphoma patients. RESULTS: We observed 4.74-fold (95% CI 4.27-5.25) and 3.40-fold (95% CI 2.78-4.10) increased risks of SPM in survivors after pediatric HL and NHL, respectively. Through over 40 years' follow-up, the cumulative incidence of SPM for pediatric lymphoma was persistently increasing, and here we firstly report the high 40-year cumulative incidence rates of SPM, 22.2% for HL and 12.6% for NHL, suggesting that SPM accounts for a great proportion of deaths among survivors. Of 6805 pediatric lymphomas, 462 (6.36%) developed a SPM, especially second breast and thyroid cancer, followed by hematologic neoplasms including leukemia and NHL. The competing risk analysis demonstrated gender, lymphoma subtype and radiotherapy were significantly associated with SPM. Different risk patterns of SPM were identified between pediatric HL and NHL. Chemotherapy accelerated SPM development but did not increase its incidence risk. CONCLUSION: Overall, patients after pediatric lymphoma can be with high lifetime risk of SPM, and more attention should be paid to SPM-related signs for early detection and intervention.

Long-term second primary cancer risk in adolescent and young adult (15-39 years) cancer survivors: a population-based study in the Netherlands between 1989 and 2018.

BACKGROUND: Few studies have comprehensively investigated the long-term second cancer risk among adolescent and young adult (AYA, aged 15-39 years) cancer survivors. This study investigated the long-term second cancer risk by including the full range of first and second cancer combinations with at least 10 observations in the Netherlands between 1989 and 2018. MATERIALS AND METHODS: First and second primary cancer data of all 6-month AYA cancer survivors were obtained from the nationwide population-based Netherlands Cancer Registry. Excess cancer risk compared to the general population was assessed with standardized incidence ratio (SIR) and absolute excess risk (AER) statistics up to 25 years after diagnosis. Cumulative incidences were estimated, using death as a competing risk factor. Analyses were carried out with and without applying multiple cancer rules. RESULTS: The cohort included 99 502 AYA cancer survivors. Male survivors had a 2-fold higher risk of developing any cancer compared to the general population, whereas this was around 1.3-fold in females. AERs were 17.5 and 10.1 per 10 000 person-years for males and females. The long-term excess risk of cancer was significantly higher for most first and second primary cancer combinations, but comparable and lower risk estimates were also observed. Application of the multiple cancer rules resulted in a noticeable risk underestimation in melanoma, testicular, and breast cancer survivors. Risk outcomes remained similar in most cases otherwise. The cumulative incidence of second cancer overall increased over time up to 8.9% in males and 10.3% in females at 25 years' follow-up. Highest long-term cumulative incidences were observed among lymphoma survivors (13.3% males and 18.9% females). CONCLUSIONS: AYA cancer survivors have a higher cancer risk compared to the general population for most cancers up to 25 years after their initial cancer diagnosis. Additional studies that investigate risk factors for the specific cancer type combinations are needed to develop personalized follow-up strategies.

Allogeneic haematopoietic cell transplantation for therapy-related myeloid neoplasms arising following treatment for lymphoma: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

Therapy-related myeloid neoplasms (t-MN), either myelodysplastic neoplasms (t-MDS) or acute myeloid leukemias (t-AML), have a poor prognosis and allogeneic haematopoietic cell transplantation (allo-HCT) represents the only curative option. In this multicenter, registry-based study, we analyzed outcomes of 378 patients undergoing first allo-HCT between 2006-2017 for t-MN arising secondary to lymphoma treatment. Median age was 58 years at allo-HCT; 222 (59%) had a diagnosis of t-MDS and 156 (41%) of t-AML, respectively. At the time of allo-HCT, 46% of t-MN cases were reported as in complete remission (CR) and 15% of lymphomas were recorded as not in remission. A reduced intensity conditioning regimen was used in 70% of cases. For the entire cohort, 5-year OS, and t-MN PFS, relapse incidence and NRM were 32%, 28%, 35% and 37%, respectively. In multivariable analysis, undergoing allo-HCT with t-MN not in CR and older age were associated with significantly worse OS, PFS and NRM. At 5 years post allo-HCT, the relapse incidence of lymphoma was low at 3%, while the rate of secondary malignancies was 8%. This analysis shows the curative potential of allo-HCT for patients with t-MN arising secondary to lymphoma treatment in approximately a third of patients.

Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem. AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors. METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6 months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92 years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60 years and older were negatively associated with CBC. CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.