Transformed follicular lymphoma with laryngeal edema requiring tracheal intubation after tisagenlecleucel treatment: A case report.

RATIONALE: Cytokine release syndrome (CRS) is a common adverse event of chimeric antigen receptor T (CAR-T) cell therapy. CRS is generally a systemic inflammatory reaction, but in rare cases, it can occur in specific body areas and is referred to as "local CRS (L-CRS)." A case of laryngeal edema due to L-CRS that required tracheal intubation because of the lack of response to tocilizumab (TCZ) and dexamethasone (DEX) is reported. PATIENT CONCERNS: A 67-year-old woman with relapsed transformed follicular lymphoma was treated with CAR-T cell therapy. Although she had been given TCZ and DEX for CRS, neck swelling appeared on day 4 after infusion. DIAGNOSES: Laryngoscopy showed severe laryngeal edema, which was presumed to be due to L-CRS, since there were no other apparent triggers based on history, physical examination, and computed tomography. INTERVENTIONS: Tracheal intubation was performed because of the risk of upper airway obstruction. Ultimately, 4 doses of tocilizumab (8 mg/kg) and 6 doses of dexamethasone (10 mg/body) were required to improve the L-CRS. OUTCOMES: On day 7, laryngeal edema improved, and the patient could be extubated. LESSONS: The lessons from this case are, first, that CAR-T cell therapy may induce laryngeal edema in L-CRS. Second, TCZ alone may be ineffective in cervical L-CRS. Third, TCZ, as well as DEX, may be inadequate. In such cases, we should recognize L-CRS and manage it early because it may eventually progress to laryngeal edema that requires securing the airway.

Long-Term Outcome of Eltrombopag With First-Line Immunosuppressive Therapy for Newly Diagnosed Severe Aplastic Anemia.

Background: To investigate whether the addition of eltrombopag (EPAG) to rabbit anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) for newly diagnosed severe aplastic anemia (SAA) improves outcomes and affects the cumulative incidence of clonal evolution (CE), we conducted a multicenter retrospective analysis. Methods: Data were collected from 101 patients, aged 15 - 65 years, undergoing initial IST. Results: No significant imbalance in age, sex, or severity was observed between the EPAG (n = 20) and non-EPAG (n = 81) groups. The median duration of EPAG administration in EPAG group was 16.1 months (range: 0.6 - 41.1 months). Six months after the initiation of IST, the complete response (CR) rate significantly improved in the EPAG group (P < 0.01). The cumulative incidence of allogeneic stem cell transplantation (allo-SCT) at 2 years and the 2-year overall survival (OS) were not significantly different between the two groups (allo-SCT, P = 0.31; OS, P = 0.64). Grade 3-4 adverse events in the EPAG group and the cumulative incidence of CE (P = 0.96) showed no increase. Conclusion: In summary, IST showed significantly better initial efficacy in the EPAG group. Although the addition of EPAG did not reduce the need for allo-SCT, no increase was observed in the incidence of CE with long-term EPAG use.

Effect of Vitamin D and Skeletal Muscle Mass on Prognosis of Patients with Diffuse Large B-Cell Lymphoma.

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0-27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77-2.5] for a low SMI and 3.2 [95% CI 1.8-5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions.

Impact of Skeletal Muscle Depletion on Patients with Myelodysplastic Syndrome Treated with Azacitidine.

BACKGROUND: Azacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated. METHODS: This retrospective, observational study included 50 MDS patients treated with AZA. Muscle mass was evaluated using the skeletal muscle index (SMI), which is the area of muscle mass at the third lumbar vertebra on CT images divided by the square of the height. RESULTS: Of the enrolled patients, 39 were males, and their median age was 69.5 years. Twenty-seven (20 male and 7 female) patients showed SMD. The median survival was 13.4 months in the SMD group and 15.2 months in the non-SMD group, with no significant difference and no significant association between the response rate or severe non-hematological toxicities and the presence of SMD. By contrast, grade 3-4 anemia and thrombocytopenia were significantly more frequent in the SMD group than in the non-SMD group. SMD was associated with severe anemia and thrombocytopenia in MDS patients treated with AZA. CONCLUSION: Reduced skeletal muscle mass may predict severe hematological toxicity in MDS patients treated with AZA.

A phase II study of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed or refractory non-Hodgkin lymphoma.

This study evaluated the efficacy and safety of salvage chemotherapy with gemcitabine, carboplatin, dexamethasone, and rituximab (GCD ± R) for Japanese patients with relapsed or refractory non-Hodgkin lymphoma (NHL). A multicenter, phase II trial of GCD ± R administered every 3 weeks for up to 6 cycles was conducted. Rituximab was administered as a therapeutic strategy for CD20-positive lymphoma. The primary endpoint was the complete response (CR) rate. Secondary endpoints included the overall response (OR) rate, overall survival (OS), progression-free survival (PFS), toxicity, and success rate of peripheral blood stem cell collection for eligible transplant patients. A total of 25 patients (median age 66 years) were evaluated, with a median follow-up period of 66.7 months. CR and OR rates were 28% and 52%, respectively. Median PFS and OS were 8.7 and 32.2 months, respectively. The major toxicity was myelosuppression, but the regimen was generally well-tolerated, with a low incidence of febrile neutropenia (20%) and no treatment-related deaths. Of the 6 patients who were eligible for autologous stem cell transplantation and underwent peripheral blood stem cell mobilization, the required number of CD34-positive cells was collected in 5 (83%). All 6 proceeded to transplantation and achieved successful engraftment without recurrence. The present results suggest that GCD ± R may be effective and well-tolerated in Japanese patients with relapsed or refractory NHL. However, further investigation is needed to confirm these results.

The pretreatment Controlling Nutritional Status score is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma.

Predicting prognosis is crucial in older patients with diffuse large B-cell lymphoma (DLBCL). This study evaluated the prognostic impact of the controlling nutritional status (CONUT) score, a simple nutritional index, for older DLBCL patients (≥65 years of age) treated with R-CHOP-like regimens in a retrospective, cohort study including 203 patients. The CONUT score was an independent prognostic factor for overall survival (hazard ratio 1.11, 95% confidence interval (CI) 1.01-1.21, p = 0.032) in a multivariable Cox proportional hazards model. On receiver-operating characteristic analysis, the optimal cutoff value was 3. The CONUT score (≥3 or <3) effectively stratified older DLBCL patients, regardless of the International Prognostic Index (p = 0.71 for interaction). Further, the CONUT score independently affected initial dose intensity (odds ratio 0.84, 95% CI 0.73-0.95, p = 0.008), likely reflecting the patients' status at diagnosis and affecting dose adjustments. In conclusion, the CONUT score is associated with a poorer prognosis in older DLBCL patients.

Comparison of the prognostic impact of IPI and PIT in peripheral T-cell lymphoma in real-world practice with a large elderly population.

We compared the predictive ability of the International Prognostic Index (IPI), a frequently used prognostic model for peripheral T-cell lymphoma (PTCL), with that of a type-specific prognostic model, the Prognostic Index for PTCL-U (PIT). We retrospectively analyzed 113 patients diagnosed with PTCL. The median age was 67 years (range, 16-88 years), 75 patients (66%) were male, and the most common disease type was PTCL, not otherwise specified (69%). With a median follow-up of 6.8 years (interquartile range, 2.7-9.9 years), 5-year survival rates for the four groups in IPI were 85%, 62%, 49%, and 13%, respectively. Similarly, 5-year survival rates for the four groups in PIT were 83%, 64%, 49%, and 19%, respectively. The area under the receiving operating characteristic curve for predicting mortality from PIT (0.725) was not significantly different from that from the IPI (0.685, P = 0.134). Multivariable analysis showed that performance status ≥ 2 (P < 0.0001) and extranodal lesions ≥ 2 (P = 0.029) were significantly associated with lower overall survival. The present study found no significant difference in prognostic ability between the IPI and PIT for PTCL, and both models appear useful as predictive models.

Japanese subgroup analysis in the Asian phase II study of darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma.

A Japanese subgroup analysis from the Asian phase II study of darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) was performed to evaluate the efficacy and safety outcomes of the Japanese population. In this Asian phase II study, darinaparsin was administered to 65 patients, including 37 Japanese patients. In the Japanese population, the histopathological type of PTCL was PTCL, not otherwise specified in 26 patients (70.3%), angioimmunoblastic T-cell lymphoma in 9 patients (24.3%) and anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) -negative in 2 patients (5.4%), and the median patient age was 70.0 (range: 43-85). 94.6% and 35.1% of the Japanese population had previously received multi-agent and single-agent regimen, respectively. The efficacy and safety were summarized and compared between the overall and Japanese populations. Based on central assessment, the overall response rate was 22.2% (8/36; 90% confidence interval [CI]: 11.6-36.5) in the Japanese population and 19.3% (11/57; 90% CI: 11.2-29.9) in the overall population. There were no essential differences in the safety profile of darinaparsin between the Japanese population and the overall population. The results of this subgroup analysis indicate that the efficacy and safety profiles of the Japanese subpopulation were broadly consistent with that of the overall population, and that darinaparsin is potentially an effective treatment with a manageable safety profile in Japanese patients with relapse or refractory PTCL.

A multicenter phase II study of bendamustine, rituximab, and cytarabine (BRAC) for relapsed or refractory patients with follicular lymphoma or mantle cell lymphoma.

This phase II clinical trial aimed to evaluate the efficacy and safety of the combination therapy of bendamustine, cytarabine, and rituximab (BRAC) in patients with relapsed or refractory follicular lymphoma (FL) or mantle cell lymphoma (MCL). Thirteen patients were enrolled and received a median of 4 cycles (range 2-6) of BRAC. The complete response rate was 61.5%, and the overall response rate was 84.6%; the 2-year overall survival was 76.9%, and the 2-year progression-free survival was 69.2%. Although all patients received G-CSF prophylaxis, grade 3 or higher neutropenia was observed in all cycles, and the incidence of febrile neutropenia was 20%. Grade 4 thrombocytopenia was observed in 92.5% of all cycles, and platelet transfusion was performed in 94%. Although hematological toxicity was relatively high, BRAC therapy was effective for relapsed and refractory FL or MCL. Further studies are needed to determine the optimal dose of BRAC therapy.Trial registration The UMIN Clinical Trials Registry, UMIN000009797. Registered 17 January 2013, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000011103.

Prognostic impact of the controlling nutritional status score in patients with peripheral T-cell lymphoma.

The controlling nutritional status (CONUT) score is a simplified nutritional index calculated from serum albumin, total cholesterol, and total lymphocyte count. This study evaluated the prognostic impact of the CONUT score on overall survival (OS) in patients with peripheral T-cell lymphoma (PTCL). A multicenter, retrospective cohort study including 99 patients with PTCL was conducted. The CONUT score was significantly higher in the non-survivor group (median 5, range 0-12) than in the survivor group (median 3, range 0-11; p = 0.026). The CONUT score was an independent prognostic factor in a multivariable Cox proportional hazards model (hazard ratio 1.119, 95% confidence interval 1.021-1.227, p = 0.017). No significant effect-modification by the International Prognostic Index (IPI) was observed, and the CONUT score affected the prognosis of PTCL regardless of the IPI (P for interaction = 0.208). In conclusion, the CONUT score is an independent prognostic factor for PTCL irrespective of IPI category.

Clinical significance of oxidative stress for untreated patients with diffuse large B-cell lymphoma.

Oxidative stress serves an important role in carcinogenesis. The present study investigated the clinical significance of oxidative stress as a prognostic factor for diffuse large B-cell lymphoma (DLBCL). The participants comprised 55 consecutive patients with DLBCL. A commercially available derivatives of reactive oxygen metabolites (d-ROMs) test kit was used to assess oxidant levels. Similarly, a commercially available biological antioxidant potential (BAP) test was used to assess antioxidant levels. The antioxidative/oxidative stress ratio was calculated as d-ROMs/BAP. The median serum concentration of d-ROMs was 425 µM. The levels of d-ROMs were significantly higher in patients with DLBCL than in healthy volunteers (P<0.01). The complete remission (CR) rates in patients with d-ROMs <425 and ≥425 µM were 81.5 and 85.7%, respectively [not significant (NS)]. The 3-year overall survival (OS) rates for patients with d-ROMs <425 and ≥425 µM were 67.2 and 72.0%, respectively (NS). The median BAP was 2,002 µM. The CR rates of patients with BAP <2,002 and ≥2,002 µM were 77.8 and 88.9%, respectively (NS). The 3-year OS rates of patients with BAP <2,002 and ≥2,002 µM were 60.9 and 75.9%, respectively (NS). No significant difference in the d-ROMs/BAP ratio was observed between groups. Multivariate analysis revealed that d-ROMs were an independent prognostic factor for progression-free survival.

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.

A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B-cell lymphoma.

Polatuzumab vedotin (pola) is a CD79b-targeted antibody-drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open-label, single-arm study of pola 1.8 mg/kg, bendamustine 90 mg/m2 , rituximab 375 mg/m2 (pola + BR) Q3W for up to six cycles in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received ≥1 prior line of therapy and were ineligible for autologous stem cell transplantation (ASCT) or experienced treatment failure with prior ASCT. Primary endpoint was complete response rate (CRR) at the end of the treatment (EOT) by positron emission tomography-computed tomography (PET-CT) using modified Lugano Response Criteria. Secondary endpoints included efficacy, safety, and pharmacokinetics. Thirty-five patients (median age 71 [range 46-86] years) were enrolled. Twenty-three (66%) patients had refractory disease, and 23 (66%) had ≥2 prior lines of therapy. At a median follow-up of 5.4 (0.7-11.9) months, patients received a median of five treatment cycles. CRR was 34.3% (95% confidence interval [CI] 19.1-52.2) at EOT. Overall response rate was 42.9% at EOT, and median progression-free survival was 5.2 months (95% CI 3.6-not evaluable). Median overall survival was not reached. No fatal adverse events (AEs) were observed. Grade 3-4 AEs were mainly hematological: anemia (37%), neutropenia (31%), white blood cell count decreased (23%), thrombocytopenia/platelet count decreased/neutrophil count decreased (20% each), and febrile neutropenia (11%). Grade 1-2 peripheral neuropathy (PN; sensory and/or motor) was reported in 14% of patients; there were no ≥grade 3 PN events. This study (JapicCTI-184048) demonstrated the efficacy and safety of pola + BR in Japanese patients with R/R DLBCL who were ineligible for ASCT.

Albumin-bilirubin score for predicting neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Ifosfamide, an alkylating agent, is widely used in the treatment of malignant diseases. However, these treatments are often limited due to the incidence of neuropsychiatric symptoms such as delirium, seizures, hallucinations and agitation. In this study, we examined risk factors for neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy. METHODS: The study cases were patients with cancer receiving ifosfamide-based chemotherapy between April 2007 and March 2018. Risk analysis for ifosfamide-related neuropsychiatric symptoms was determined by time-dependent Cox proportional hazard regression analysis. RESULTS AND DISCUSSION: Of 183 eligible patients, 32 patients (17.5%) experienced ifosfamide-related neuropsychiatric symptoms. Time-dependent Cox proportional hazard model showed that the albumin-bilirubin (ALBI) score was significantly correlated with the incidence of ifosfamide-related neuropsychiatric symptoms (hazard ratio [HR] =1.45, 95% confidence interval [CI] = 1.05-2.01, p = 0.025). Additionally, there were correlations between the predicted risk of neuropsychiatric symptoms and ifosfamide-dose per cycle (HR =0.51, 95% CI = 0.27-0.94, p = 0.030) and creatinine clearance (Ccr) (HR = 0.53, 95% CI = 0.28-1.00, p = 0.050). In contrast, neither serum albumin nor total bilirubin was a significant risk factor for neuropsychiatric symptoms. WHAT IS NEW AND CONCLUSION: These findings indicate that ALBI score may be a useful biomarker for predicting neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy.

Development of diffuse large B-cell lymphoma after sofosbuvir-ledipasvir treatment for chronic hepatitis C: A case report and literature review.

Recently, treatments for chronic hepatitis C virus (HCV) infection have significantly improved by the development of direct-acting antiviral agents (DAAs) and almost all patients with HCV can complete antiviral treatment without apparent adverse events. Malignant lymphoma, particularly B-cell non-Hodgkin's lymphoma, is one of the extrahepatic manifestations associated with chronic HCV infection. The effectiveness of anti-HCV therapy with DAAs for B-cell non-Hodgkin's lymphoma has been demonstrated in recent reports, whereas late-onset B-cell non-Hodgkin's lymphoma after HCV eradication with DAAs has occasionally been reported. In the present study, a 77-year-old man with chronic hepatitis C and intermediate liver cancer risk received sofosbuvir-ledipasvir treatment for 12 weeks. Two months following the end of antiviral therapy, he had achieved sustained virologic response for 8 weeks. However, the patient occasionally found swelling of the right cervical lymph nodes without any subjective symptoms. Lymph node biopsy revealed diffuse large B-cell lymphoma and whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography showed increased FDG uptake in the right cervical, right submandibular, mediastinal and mesenteric lymph nodes. The patient received six courses of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and achieved complete response at 8 months after chemotherapy initiation. Thus, the development of lymphoid malignancies may arise, even after HCV eradication with DAAs. Therefore, clinicians should be aware of such risks during and after antiviral treatment with DAAs.

Comparison of breakthrough Gram-positive cocci infection during vancomycin vs teicoplanin therapy in patients receiving haematopoietic stem cell transplantation.

WHAT IS KNOWN AND OBJECTIVE: Our previous report indicated that teicoplanin (TEIC) caused fewer adverse effects than vancomycin (VCM) in patients with febrile neutropenia (FN) receiving haematopoietic stem cell transplantation (HSCT). However, we observed breakthrough methicillin-resistant-Staphylococcus haemolyticus (MR-S haemolyticus) infection during TEIC therapy in these patients. In this study, we sought to compare the incidence of breakthrough Gram-positive cocci (GPC) infection during VCM and TEIC therapy in this population. METHODS: A single-centre, retrospective cohort study was conducted. Patients who had received HSCT and were administered VCM (n = 19) or TEIC (n = 38) for FN from 1 September 2011 to 31 August 2019 were enrolled. We compared the incidence of breakthrough GPC infection between the VCM and TEIC groups. RESULTS: Breakthrough GPC infection during glycopeptide therapy in febrile neutropenic patients received HSCT was observed in three patients (7.9%) in the TEIC group but in none of patients (0%) in the VCM group. MR-S haemolyticus with low glycopeptide susceptibility (TEIC MIC = 2-8 µg/mL, VCM MIC = 2-4 µg/mL) was isolated from blood cultures in all patients with breakthrough GPC infections. All breakthrough infections were cured by changing from TEIC to daptomycin (DAP). WHAT IS NEW AND CONCLUSION: The incidence of breakthrough GPC infection during glycopeptide therapy in febrile neutropenic HSCT patients was higher in the TEIC group than in the VCM group. MR-S haemolyticus with low glycopeptide susceptibility was isolated from all patients with breakthrough GPC infection and successfully treated with DAP.

[Acquired hemophilia A complicated by dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid].

A 72-year-old man developed dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid (BP) during treatment for type 2 diabetes mellitus and was administered prednisolone (PSL, 0.5 mg/kg). Despite PSL treatment at a daily dose of 19 mg/day, purpura appeared on his bilateral forearms 3 months later. He was diagnosed with acquired hemophilia A (AHA) based on a prolonged activated partial thromboplastin time, decrease in factor VIII activity, and the presence of factor VIII inhibitor. Immunosuppressive therapy (IST) comprising PSL (1 mg/kg) and cyclophosphamide (300 mg/week) did not reduce the inhibitor level, and he subsequently developed the complication of pneumonia caused by a fungal infection. Weekly rituximab (RTX) therapy (375 mg/m2) for 4 weeks not only reduced the inhibitor level, but also enabled a rapid PSL dose reduction. Finally, a coagulative complete remission was achieved with improvements in pneumonia and BP. The prevention of adverse events of IST is particularly important in patients with AHA, who have a high median age. Therefore, RTX-based IST may be safer for AHA patients with complicating infections.

Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy.

Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship between skeletal muscles and low levels of tryptophan. A positive correlation was observed between the volume of skeletal muscles and serum tryptophan levels in patients with diffuse large B-cell lymphoma. Low levels of tryptophan reduced C2C12 myoblast cell proliferation and differentiation. Fiber diameters in the tibialis anterior of C57BL/6 mice fed a tryptophan-deficient diet were smaller than those in mice fed a standard diet. Metabolomics analysis revealed that tryptophan-deficient diet downregulated glycolysis in the gastrocnemius and upregulated the concentrations of amino acids associated with the tricarboxylic acid cycle. The weights and muscle fiber diameters of mice fed the tryptophan-deficient diet recovered after switching to the standard diet. Our data showed a critical role for tryptophan in regulating skeletal muscle mass. Thus, the tryptophan metabolism pathway may be a promising target for preventing or treating skeletal muscle atrophies.

Prospective evaluation of alternative donor from unrelated donor and cord blood in adult acute leukemia and myelodysplastic syndrome.

A prospectively registered observational study was conducted to assess the significance of allogeneic hematopoietic stem cell transplantation from highly HLA-matched unrelated donors (UD) and cord blood (CB) on outcomes in adult acute leukemia (AL) and myelodysplastic syndrome (MDS). Between 2007 and 2015, 231 transplant-eligible patients were registered for a phase 2 study of alternative donor transplantation. After registration, a sufficient time period was given to find appropriate UD. Patients received CB transplantation (CBT) if an appropriate UD was unavailable. In total, 119 patients received CBT (106 AL and 13 MDS) and 91 patients received UD transplantation (UDT) (86 AL and 5 MDS). The median age was 39 years in both groups. The primary objective was overall survival (OS); secondary objectives included cumulative incidences of non-relapse mortality (NRM) and relapse, and disease-free survival. Diagnosis, disease status at transplantation, refined disease risk index, and hematopoietic cell transplant-specific comorbidity index did not differ between UDT and CBT. In multivariate analyses, graft source was not a significant risk factor for all objectives. In adjusted analyses, UDT and CBT showed similar OS, NRM, and relapse in this prospective study. CB can be a comparable alternative stem cell source to UD by achieving a timely transplant.