The prognosis and risk factors for patients with complex karyotype myelodysplastic syndrome undergoing allogeneic haematopoietic stem cell transplantation.

Allogeneic haematopoietic stem cell transplantation (HCT) is the curative treatment for myelodysplastic syndrome with a complex karyotype (CK-MDS). However, only a few studies have been limited to patients with CK-MDS undergoing allogeneic HCT. This study aimed to identify the risk factors for patients with CK-MDS undergoing allogeneic HCT. We included 691 patients with CK-MDS who received their first allogeneic HCT. The overall survival (OS) was the primary end-point, estimated using the Kaplan-Meier method. Prognostic factors were identified using a Cox proportional hazards model. The 3-year OS was 29.8% (95% confidence interval [CI]: 26.3-33.3). In the multivariable analysis, older age (hazard ratio [HR]: 1.44, 95% CI: 1.11-1.88), male sex (HR: 1.38, 95% CI: 1.11-1.71), poor haematopoietic cell transplant comorbidity index (HR: 1.47, 95% CI: 1.20-1.81), red blood cell transfusion requirement (HR: 1.58, 95% CI: 1.13-2.20), platelet transfusion requirement (HR: 1.85, 95% CI: 1.46-2.35), not-complete remission (HR: 1.55, 95% CI: 1.16-2.06), a high number of karyotype abnormality (HR: 1.63, 95% CI: 1.18-2.25) and monosomal karyotype (HR: 1.49, 95% CI: 1.05-2.12) were significantly associated with OS. Thus, the 3-year OS of allogeneic HCT was 29.8% in patients with CK-MDS, and we identified risk factors associated with poor OS.

Comparative outcomes of various transplantation platforms, highlighting haploidentical transplants with post-transplantation cyclophosphamide for adult T-cell leukaemia/lymphoma.

This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo-HCT) platforms in patients with adult T-cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)-haploidentical-related donors using post-transplant cyclophosphamide (PTCY), HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo-HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non-relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow-up of 794 days for survivors, 2-year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2-year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft-versus-host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo-HCT with PTCY is a safe and effective platform for patients with adult T-cell leukaemia/lymphoma.

Association of individual comorbidities with outcomes in allogeneic hematopoietic cell transplantation from unrelated adult donors versus unrelated cord blood: A study on behalf of the Donor/Source and Transplant Complications Working Groups of the Japanese Society for Transplantation and Cellular Therapy.

We retrospectively evaluated the effect of 17 individual comorbidities, defined by the hematopoietic cell transplantation (HCT)-specific comorbidity index, on non-relapse mortality (NRM) and overall survival (OS) in 9531 patients aged between 16 and 70 years who underwent their first allogeneic HCT from 8/8 and 7/8 allele-matched unrelated donors (8/8 and 7/8 MUDs) or single-unit unrelated cord blood (UCB) between 2011 and 2020 using data from a Japanese registry database. In the multivariate analysis, infection (adjusted hazard ratio [HR], 1.62, 95% confidence interval [CI], 1.33-1.99 for 8/8 and 7/8 MUDs; adjusted HR, 1.33, 95%CI, 1.12-1.58 for UCB) and moderate/severe hepatic comorbidity (adjusted HR, 1.57, 95%CI, 1.04-2.38 for 8/8 and 7/8 MUDs; adjusted HR, 1.53, 95%CI, 1.09-2.15 for UCB) had a significant impact on NRM in both donor groups. Cardiac comorbidity (adjusted HR, 1.40, 95%CI, 1.08-1.80), mild hepatic comorbidity (adjusted HR, 1.22, 95%CI, 1.01-1.48), rheumatologic comorbidity (adjusted HR, 1.67, 95%CI, 1.11-2.51), renal comorbidity (adjusted HR, 2.44, 95%CI, 1.46-4.09), and severe pulmonary comorbidity (adjusted HR, 1.40, 95%CI, 1.11-1.77) were significantly associated with an increased risk of NRM but only in UCB recipients. Renal comorbidity had the strongest impact on poor OS in both donor groups (adjusted HR, 1.73, 95%CI, 1.10-2.72 for 8/8 and 7/8 MUDs; adjusted HR, 2.24, 95%CI, 1.54-3.24 for UCB). Therefore, unrelated donor selection should be taken into consideration along with the presence of specific comorbidities, such as cardiac, rheumatologic, renal, mild hepatic, and severe pulmonary comorbidities.

Swim-up method is superior to density gradient centrifugation for preserving sperm DNA integrity during sperm processing.

Purpose: This study aimed to evaluate the effects of swim-up and density gradient centrifugation methods on sperm DNA fragmentation. Methods: Nineteen normozoospermic patient samples with ≥100 × 106 motile sperms were included in this study. Sperm DNA fragmentation, progressive motility, and progressive motile sperm number were measured before and after the swim-up method or density gradient centrifugation. Results: Sperm DNA fragmentation was not statistically different between swim-up-(14.4 ± 2.1%, p = 0.32) and density gradient centrifugation-processed (25.0 ± 3.0%, p = 0.20) and unprocessed semen samples (19.2 ± 1.9%). Sperm DNA fragmentation was significantly lower in swim-up-than in density gradient centrifugation-processed samples (p < 0.05). Sperm progressive motility was significantly higher (p < 0.05) in swim-up-(92.9 ± 1.0%) and density gradient centrifugation-processed (81.3 ± 2.0%) samples, with the former being higher, than in unprocessed semen samples (53.1 ± 3.7%). The recovery rate of progressive motile sperms was significantly lower in swim-up-(9.7 ± 1.4%) than in density gradient centrifugation-processed samples (17.2 ± 1.8%, p < 0.05). Conclusions: The swim-up method is superior to density gradient centrifugation, evidenced by less sperm DNA fragmentation and higher sperm progressive motility. The recovery rate of progressive motile sperms was better after density gradient centrifugation than after swim-up.

Lenalidomide treatment for recurrent adult T-cell leukemia/lymphoma after allogeneic hematopoietic cell transplantation.

Patients with recurrent adult T-cell leukemia/lymphoma (ATL) after allogeneic hematopoietic cell transplantation (allo-HCT) have a dismal prognosis. We retrospectively evaluated the safety and efficacy of lenalidomide (LEN) in 11 consecutive patients with recurrent ATL after allo-HCT. The median time from allo-HCT to ATL recurrence was 111 days (range, 20-1476), and that from allo-HCT to the initiation of LEN was 162 days (range, 43-1560). The median initial daily dose of LEN was 10 mg (range, 5-25), and the median duration of LEN treatment was 37 days (range, 3-1078). Three patients (27%) achieved complete response and two (18%) achieved partial response (PR). The rates of complete or PR according to the involved site were 57% for skin and 50% for nodal or extranodal lesions. With a median follow-up of 1033 days (range, 601-1465) among survivors, the 1-year probability of overall survival (OS) after ATL recurrence was 55%. Grade ≥3 toxicities included cytopenia (n = 4), superficial vein thrombosis (n = 1), and deep vein thrombosis (n = 1). Graft-versus-host disease (GVHD) newly developed in five patients (45%) and worsened in four patients (36%). The median duration from the initiation of LEN to GVHD onset or worsening was 5 days (range, 1-9). GVHD was manageable in all patients. Seven patients received mogamulizumab (MOG) for recurrent ATL before LEN treatment. The overall response rates to LEN were 57% in patients who had previously received MOG and 25% in those who had not. The 1-year probabilities of OS after recurrent ATL were 71% in patients who had previously received MOG and 25% in those who had not. Although cytopenia and GVHD are common among patients with recurrent ATL after allo-HCT, LEN may improve survival. Administering MOG before LEN may augment treatment efficacy in the allo-HCT population.

Optimal timing to retrieve oocytes for fertility preservation in patients with acute myeloid leukemia: two cases of controlled ovarian stimulation using DuoStim with a literature review.

Fertility preservation (FP) for hematological malignancies is difficult because immediate chemotherapy is needed after diagnosis. We report two cases of acute myeloid leukemia (AML) treated with controlled ovarian stimulation (COS) and oocyte cryopreservation using DuoStim after first-line chemotherapy. In Cases 1 and 2, COS and oocyte retrieval (OR) were performed using DuoStim 116 and 51 days after first-line chemotherapy, respectively, and 14 and 6 unfertilized oocytes, respectively, were cryopreserved. Another round of COS and OR was performed using the random-start method 82 days after first-line chemotherapy, and 22 unfertilized oocytes were cryopreserved. DuoStim is useful to maximize OR for patients with a short interval for FP. Many oocytes can be retrieved depending on the timing of recruitment from primary to secondary follicles, although ovarian reserve capacity declines immediately after first-line chemotherapy. Aggressive FP should be performed before allogeneic hematopoietic stem cell transplantation becomes necessary.

Prognostic implication of CTLA-4, PD-1, and PD-L1 expression in aggressive adult T-cell leukemia-lymphoma.

The prognosis of patients with aggressive adult T cell leukemia-lymphoma (ATLL) is dismal even with intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation (HSCT) is a promising option for patients with aggressive ATLL, but the posttransplant outcome remains unsatisfactory. Hence, to further improve clinical outcomes, novel therapeutic approaches are needed. The clinical significance of immune checkpoint protein expression has not been well-established in aggressive ATLL. This study aims to identify the association between the expression profile of immune checkpoint proteins on ATLL cells and clinical outcomes. This retrospective study cohort included 65 patients with aggressive ATLL diagnosed between 2001 and 2015 at the National Cancer Center Hospital, Tokyo, Japan. Formalin-fixed paraffin-embedded tissue was used to immunohistochemically determine the expression of immune checkpoint proteins and assess the impact of expression profile on the probability of overall survival from diagnosis or HSCT. The current analysis shows that cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) expressions were adverse prognostic factors in patients with aggressive ATLL. Experiments that assess the efficacy of immune checkpoint inhibitors are warranted to alleviate the adverse impacts associated with negative immune checkpoints.

Feasibility and usefulness of recommended screenings at long-term follow-up clinics for hematopoietic cell transplant survivors.

PURPOSE: Advances in allogeneic hematopoietic cell transplantation (allo-HCT) have resulted in a growing number of transplant survivors; however, long-term survivors are at risk of developing late complications, and published guidelines recommend screening of this population. We conducted a single-center prospective study to evaluate the adherence to and usefulness of recommended screenings at a long-term follow-up (LTFU) clinic. METHODS: We included consecutive patients who received allo-HCT at our center from 2014, as well as post-HCT patients visiting our outpatient clinic. Visits and screenings were planned at 3 months, 6 months, and 1 year after allo-HCT, and annually thereafter. Outcomes were reported by physicians including the incidence of findings at each screening that led to interventions. RESULTS: Among the 216 participants, 95% visited the LTFU clinic, and 94% completed planned screenings. However, the rate of secondary cancer screenings targeting high-risk subjects was lower (38% to 68%). The overall percentage of screening results leading to interventions was 4.5%, with higher percentages (> 10%) for bone density testing, ophthalmological examinations, dental assessment, upper gastrointestinal endoscopy, and colonoscopy, with two patients diagnosed with secondary cancers. CONCLUSIONS: Although the overall screening rate was high, it should be possible to improve the detection rate of late complications by decreasing screening failures, especially the screening for secondary cancers limited for high-risk survivors. A nationwide effort to educate HCT survivors and health practitioners using standardized nationwide LTFU tools may be effective, along with the development of institutional, local, and nationwide networks to maintain effective follow-up systems.

Outcomes of hematopoietic cell transplantation for transformed follicular lymphoma.

This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low-dose anti-thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT-specific comorbidity index were similar between the two groups. With a median follow-up of 5.8 years among survivors, the 5-year probability of progression-free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5-year cumulative incidence of non-relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5-year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low-dose anti-thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced-phase tFL achieved long-term progression-free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression.

Usefulness of hematopoietic progenitor cell monitoring to predict autologous peripheral blood stem cell harvest timing: A single-center retrospective study.

INTRODUCTION: In autologous peripheral blood stem cell harvest (APBSCH), CD34-positive cells have been measured to assess the numbers of hematopoietic stem cells, but measurement requires specialized equipment. Recently, there was a report that peripheral blood hematopoietic progenitor cells (HPCs) are useful indicators of the presence of hematopoietic stem cells. We examined the usefulness of HPC monitoring to predict APBSCH timing. METHODS: We retrospectively analyzed the relationship between HPC and collected CD34-positive cells in 84 consecutive patients who underwent APBSCH. RESULTS: According to the receiver operating characteristics curve for the collection of ≥2 × 106 CD34-positive cells/kg, the HPC cut-off value on the day before collection was 21/µL, while that on the day of collection was 41/µL. No significant factors were found in the univariate analysis except for the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001). According to the multivariate analysis, the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001) were also factors that strongly influenced the quantity of CD34-positive cells collected. CONCLUSION: Our results suggest that the HPC count on not only the day of collection but also the day before collection is a good indicator for appropriate APBSCH timing.

iPREFACE score: Integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring.

AIM: Cardiotocography is used worldwide to evaluate fetal well-being during pregnancy and labor. In past guidelines, the management plan was determined based on the assessment of the most severe waveform. There are no guidelines for evaluating the integrated recurrent decelerations; however, we believe their assessment to be essential for predicting the status of the fetus. The objective of this study was to propose an indicator for performing medical interventions during labor by creating a scoring system that reflects integrated recurrent decelerations. METHODS: In this retrospective cohort study, we included data for only full-term single fetus births from vaginal deliveries. The score named the iPREFACE score (integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring) was calculated using cardiotocography findings from continuing 30 min before delivery. We examined the iPREFACE score and fetal acidemia association and calculated the cut-off iPREFACE scores for acidemia using receiver operating characteristic curves. RESULTS: The study included 469 delivery cases. Their iPREFACE scores exhibited a significant negative correlation with the umbilical artery blood pH (correlation coefficient; -0.43). The cut-off iPREFACE scores for the umbilical artery blood with pH <7.20, <7.10 and <7.0 were 44, 46 and 67, respectively (the areas under the curve were 0.776, 0.962 and 0.996, respectively). CONCLUSION: The iPREFACE score may predict fetal acidemia and could be used as an indicator for timely medical interventions during labor. Because assessments using a cardiotocography are quick and easy to perform, the iPREFACE score could be a valuable tool in clinical practice.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for ATL with HTLV-1 Antibody-Positive Donors.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative treatment option for patients with aggressive adult T cell leukemia-lymphoma (ATL). Donor human T cell leukemia virus (HTLV) 1 seropositivity is a critical concern when choosing relative donors, as they are not usually recommended due solely to the occurrence of donor-derived ATL. A previous report suggested that allo-HCT with an HTLV-1-seropositive donor increased ATL-related mortality. We updated the risk assessment for choosing an HTLV-1-seropositive allo-HCT donor for ATL. Our current registry data, which include larger numbers of HTLV-1-seropositive donors and longer observation periods, revealed no significant difference in overall survival (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.70-1.24; P = .61) or cumulative incidence of either ATL-related (HR, 0.96; 95% CI, 0.64 to 1.45; P = .80) or non-ATL-related mortality (HR, 0.91; 95% CI, 0.61 to 1.37; P = .66). Similarly, when considering only patients with ATL in complete remission, there was no significant difference in overall survival (HR, 1.02; 95% CI, 0.70 to 1.49; P = .91) or cumulative incidence of either ATL-related (HR, 1.20; 95% CI, 0.66 to 2.20; P=0.54) or non-ATL-related mortality (HR, 0.86; 95% CI, 0.52-1.42; P = .66). These data indicate that selecting HTLV-1-seropositive donors might not be contraindicated for patients with ATL receiving allo-HCT if alternative donors are unavailable. Further risk assessment remains to be performed.

Capsule Endoscopy after Hematopoietic Stem Cell Transplantation Can Predict Transplant-Related Mortality.

BACKGROUND AND OBJECTIVES: Allogenic hematopoietic stem cell transplantation (allo-SCT) is a curative therapy for hematological malignancies, but transplant-related mortality (TRM) remains a concern. This study aimed to determine the efficacy of capsule endoscopy (CE) by evaluating the correlation between inflammatory findings on CE and TRM. METHODS: The data of patients after allo-SCT were retrospectively collected. The association between findings on CE and TRM at 100 days from the CE was evaluated. RESULTS: Of the 94 patients included in the study, 47 showed inflammatory findings on CE. The findings were diagnosed as graft-versus-host disease (GVHD; n = 17), cytomegalovirus (CMV) infection (n = 14), and GVHD with CMV infection (n = 16). Of the 47 patients, 13 (28%) had TRM. Endoscopic diagnoses of these TRM cases were GVHD (n = 4), CMV infection (n = 0), and GVHD with CMV infection (n = 9). In contrast, in the remaining 47 patients who showed no inflammatory findings on CE, 2 patients (4%) had TRM. The proportion of TRM was higher in patients with inflammatory findings than in those without it (28 vs. 4%, p < 0.01). CONCLUSIONS: CE may predict TRM in patients who developed gastrointestinal symptoms after allo-SCT.

DuoStim: a new option for fertility preservation for a woman with Turner syndrome.

INTRODUCTION: Turner syndrome (TS) is associated with hypergonadotropic hypogonadism due to gonadal dysgenesis, which results in premature ovarian failure and subsequent infertility. Therefore, counseling and evaluation for fertility preservation are required as early as possible for women with TS. CASE PRESENTATION: A 23-year-old unmarried woman with mosaic TS (45, X [4/30] 46, XX [26/30]) presented to the pediatric department of our hospital for fertility counseling; she was accompanied by her mother. She was referred to the reproduction center of our hospital for ovarian reserve assessment and counseling regarding fertility preservation. We decided to retrieve oocytes using DuoStim as the controlled ovarian stimulation protocol. During the first and second oocyte retrievals, a total of 17 (9 and 8, respectively) mature metaphase II oocytes were cryopreserved. CONCLUSION: DuoStim may be a useful option for fertility preservation for women with TS and reduced ovarian reserve. This new strategy may obtain the required number of oocytes in the shortest time and preserve the future fertility of women with TS.

[Successful treatment of very severe late-onset sinusoidal obstruction syndrome with recombinant human soluble thrombomodulin, steroids, and control of intra-abdominal pressure].

We report a case of a 16-year-old woman who achieved her third complete remission of acute lymphoblastic leukemia after undergoing allogeneic stem cell transplantation for the second time from an unrelated donor. On post-transplantation day 30, she showed weight gain, hepatomegaly, right hypochondriac pain, and ascites. On day 35, ultrasonography (US) revealed portal vein regurgitation. She was subsequently diagnosed with late-onset sinusoidal obstruction syndrome (SOS) and was transferred to the intensive care unit (ICU) on day 36 for multiple organ dysfunction syndrome (MODS) and disseminated intravascular coagulation, requiring mechanical ventilation. Her SOS was graded as very severe upon ICU admission. Recombinant human soluble thrombomodulin (380 U/kg/day) and methylprednisolone (2 mg/kg/day) therapies were initiated. Additionally, her intra-abdominal pressure had increased to 19 mmHg, which was thought to be the cause of MODS. Ascites drainage (1,000 ml/day), according to the treatment for abdominal compartment syndrome, improved her SOS and MODS. She was weaned from mechanical ventilation on the 10th day after ICU transfer, and US showed resolution of the portal vein regurgitation. She was transferred to the general ward on the 14th day. She had not experienced disease recurrence at her last visit (527 days after the second transplantation).

Characterization of Late Acute and Chronic Graft-Versus-Host Disease according to the 2014 National Institutes of Health Consensus Criteria in Japanese Patients.

To characterize the incidences and outcomes of late acute (LA) and chronic graft-versus-host disease (GVHD) in East Asians according to the 2014 National Institutes of Health criteria, we retrospectively analyzed 506 consecutive Japanese patients who had a first allogeneic hematopoietic cell transplantation (HCT) at our center between 2006 and 2013. According to manifestations at onset 91 patients (60%) had LA GVHD and 60 (40%) had chronic GVHD. The cumulative incidences of LA and chronic GVHD were 20% and 17%, respectively, at 48 months after HCT. The involved sites at the onset of LA GVHD included the skin (71%), gut (13%), and liver (8%). The cumulative incidences of relapse, nonrelapse mortality (NRM), transition to chronic GVHD, and discontinued systemic treatment were 11%, 6%, 22%, and 46%, respectively, at 48 months after onset of LA GVHD. Cox models showed that prior acute GVHD was associated with NRM, and HCT from a female donor to a male patient, myeloablative conditioning, and low Karnofsky performance status were associated with a longer duration of systemic treatment after LA GVHD. The most frequently involved sites at the onset of chronic GVHD included the mouth (83%), liver (75%), skin (69%), and eyes (62%). Cox models showed that use of antithymocyte globulin in conditioning regimens was associated with a higher risk of discontinued systemic treatment after the onset of chronic GVHD. The cumulative incidences of relapse, NRM, and discontinued systemic treatment were 16%, 11%, and 41%, respectively, at 48 months after the onset of chronic GVHD. Our results suggested several potential differences between Japanese patients and those of other ethnicities. A direct comparison is needed to formally investigate ethnic differences.

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor specific to the programmed death 1 (PD-1) receptor. Nivolumab has shown clinical responses in many malignancies. Although immune-related adverse events (irAEs) associated with nivolumab are largely tolerable, severe irAEs have occurred in some patients. However, the mechanisms underlying the development of irAEs are not fully clarified. CASE PRESENTATION: We report 2 patients with metastatic melanoma who developed colitis, an irAEs caused by nivolumab. Both patients experienced colitis after nivolumab administration. Pathological examination of the colon showed robust infiltration of CD8+ cells and T-bet expressing CD4+ cells in both cases, indicating helper T cells (Th) 1 to be responsible for the dominant response. Additionally, we observed the serum C-reactive protein level (CRP) as well as interleukin-6 (IL-6) reflected the clinical course of irAEs clearly in the two cases. CONCLUSION: Our two cases suggested that the development of irAEs due to nivolumab is associated with Th1 dominant response. CRP as well as IL-6 was found to be a potential biomarker for irAEs. Our findings may help to understand the mechanisms underlying irAEs caused by nivolumab and manage irAEs in clinical practice.

Association of CD204+ macrophages with poor outcomes of malignant lymphomas not in remission treated by allogeneic HCT.

OBJECTIVE: CD204+ tumor-associated macrophages are associated with adverse outcomes of various malignancies. We performed a study to elucidate the role of CD204+ macrophages in allogeneic hematopoietic cell transplantation (allogeneic HCT). METHODS: In a total of 81 patients who received allogeneic HCT for non-remission malignant lymphoma, immunohistochemical staining of CD204 using specimens preserved before allogeneic HCT was performed. According to the average number of CD204+ macrophages in a high-power field, patients were categorized into three groups: low (<25th percentile), intermediate (≥25th percentile and <50th percentile), and high (≥50th percentile). RESULTS: The B-cell lymphoma proportion was higher in the low group, while T-cell lymphoma and adult T-cell leukemia proportions were higher in the high group. The 3-year overall survival (OS) was poorest in the high group; low vs intermediate vs high = 83.3% vs 43.7% vs 20.2% (P < .01). The 3-year cumulative incidences of relapse were significantly higher in the high group than the intermediate and low groups: 67.0% vs 38.1% vs 18.2% (P < .01). In multivariate analyses, the numbers of CD204+ macrophages were independent risk factors of poorer OS and cumulative incidences of relapse. CONCLUSIONS: CD204+ macrophages might be associated with poorer prognosis in allogeneic HCT for malignant lymphomas.

Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation.

Double-expressor lymphoma (DEL) is a diffuse large B cell lymphoma that exhibits co-expression of MYC and BCL2 proteins by immunohistochemistry. Patients with double-expressor lymphoma have a poor prognosis after standard chemoimmunotherapy or after high-dose chemotherapy with autologous transplantation, but the prognostic impact of DEL after allogeneic hematopoietic cell transplantation has not been well characterized. We retrospectively analyzed 60 consecutive patients with de novo diffuse large B cell lymphoma or transformed follicular lymphoma who underwent allogeneic transplantation at our center and had available immunohistochemistry data. Thirty-seven patients (62%) had DEL. The 2-year progression-free and overall survival rates were lower in patients with DEL than in those without DEL (20% versus 78%; overall P <.001 and 46% versus 77%; overall P = .016, respectively). The cumulative incidence of disease progression at 2 years was higher in patients with DEL (60% versus 13%; overall P = .005). The cumulative incidence of nonrelapse mortality did not differ statistically in the 2 groups. Even in patients with DEL and chemosensitive disease at transplantation, the 2-year progression-free survival rate was only 27% due to early disease progression. Multivariate analysis showed associations between DEL and increased risks of progression-free survival events (hazard ratio [HR], 4.58; 95% confidence interval [CI], 2.07-10.2; P <.001), overall mortality (HR, 2.29; 95% CI, 1.03-5.09; P = .042) and disease progression (HR, 3.60; 95% CI, 1.38-9.44; P = .009). Patients with DEL had poor outcomes after allogeneic transplantation. Innovative strategies are needed to improve outcomes in this population.

Ultrasound-guided laparotomic oocyte retrieval during surgery for fertility preservation in a case of tumor recurrence after a unilateral salpingo-oophorectomy.

Case: A 28 year old unmarried woman underwent a unilateral salpingo-oophorectomy and was suspected of having a malignant tumor in the remaining ovary. After consultation with the patient and her family, it was decided to cryopreserve the unfertilized oocytes. In order to reduce the risk of puncturing or rupturing the tumor when performing the oocyte retrieval from the ovary that was affected by the malignant tumor, it was chosen to use direct laparotomic oocyte retrieval during surgery, instead of conventional transvaginal retrieval. In order to further reduce the risk of tumor rupture, an ultrasound was used in the laparotomy field to precisely puncture only the follicle and thus avoid the tumor. A total of 11 oocytes was retrieved and 10 of them were cryopreserved in the MII phase. Outcome: By using an ultrasound at the same time as the oocyte retrieval, it was possible to avoid the ovarian tumor site. Furthermore, by checking and puncturing the follicles, it became possible to retrieve oocytes from the healthy parts of the ovary with greater precision. The combined use of an ultrasound with oocyte retrieval can be considered to be an effective method because it can be performed relatively easily. Conclusion: The authors believe that not only macroscopic, but also ultrasonic, methods are useful to reduce the risk of tumor rupture.