Central nervous system mucormycosis in a patient with hematological malignancy: A case report and review of the literature.

Invasive mucormycosis is a refractory fungal infection. Central nervous system (CNS) mucormycosis is a rare complication caused by infiltration from the paranasal sinuses or hematogenous dissemination. Here, we present a case of a brain abscess, due to mucormycosis, diagnosed using burr craniotomy. A 25-year-old Japanese woman with relapsed-refractory acute lymphoblastic leukemia underwent cord blood transplantation (CBT). The patient experienced prolonged and profound neutropenia, and oral voriconazole was administered as primary antifungal prophylaxis. The patient received a conditioning regimen on day -11 and complained of aphasia and right hemiparesis on day -6. Magnetic resonance imaging (MRI) revealed a T2-weighted high-intensity area in the left frontal cortex. A brain abscess was suspected, and liposomal amphotericin B (L-AMB) administration was started. The patient underwent CBT as scheduled and underwent neutrophil engraftment on day 14. Although the patient achieved complete remission on day 28, her consciousness level gradually deteriorated. MRI revealed an enlarged brain lesion with a midline shift sign, suggesting brain herniation. Craniotomy was performed to relieve intracranial pressure and drain the abscess on day 38, and a diagnosis of cerebral mucormycosis was confirmed. The L-AMB dose was increased to 10 mg/kg on day 43. Although the patient's consciousness level improved, she died of hemorrhagic cystitis and aspiration pneumonia. Cerebral mucormycosis should be suspected if neurological symptoms are observed in stem cell transplant recipients. Prompt commencement of antifungal therapy and debridement are crucial because mucormycosis has a poor prognosis.

[Clinical features of thyroid dysfunction in adult Japanese after allogeneic hematopoietic stem cell transplantation].

We examined the incidence and clinical features of thyroid dysfunction in 661 patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our hospital. At a median of 2.5 (1.0-11.3) years, 28 patients (4.2%) developed subclinical hypothyroidism, and 16 patients (2.4%) developed hypothyroidism. Eight of 16 patients (50%) with hypothyroidism were positive for anti-thyroid antibodies. Ten of 44 patients (22.7%) with thyroid dysfunction were discovered more than 5 years after allo-HSCT. Thyroid dysfunction with late onset was common in allo-HSCT recipients, and thyroid function should be monitored on a regular basis.

[Late-onset refractory autoimmune hemolytic anemia following autologous hematologic recovery after allo-HSCT in aplastic anemia-PNH syndrome].

A 31-year-old man underwent allogeneic bone marrow transplantation (BMT) for the treatment of transfusion-dependent aplastic anemia (AA) after conditioning with a regimen including fludarabine, cyclophosphamide, and antithymocyte globulin. The patient developed a late graft rejection on day 103 and showed autologous hematologic recovery not requiring transfusions on day 76. Peripheral blood leukocytes were of 100% recipient origin on day 103, and paroxysmal nocturnal hematuria (PNH)-type granulocytes were detected 5 months after BMT. The patient suddenly experienced hemolytic symptoms triggered by cold stimulation, and was diagnosed with autoimmune hemolytic anemia (AIHA) 37 months after BMT. Although anemia was ameliorated by prednisolone (PSL), hemolytic attacks repeatedly occurred, which became refractory to corticosteroids. Moreover, the patient underwent a splenectomy for the steroid-resistant AIHA and achieved AIHA remission without the need for PSL at 53 months after BMT. The immune tolerance breakdown to erythrocyte antigens was thought to have occurred due to various factors including immune AA, medication, cold stimulation, and infection, leading to AIHA development in this case.

[A favorable clinical course of acute myeloid leukemia with t (6;21;8)(p23;q22;q22)].

Variants of the t (8;21) (q22;q22) involving chromosome 8, 21, and other chromosomes account for about 3% of all t (8;21) (q22;q22) in patients with acute myeloid leukemia (AML). However, the prognosis of AML with variant t (8;21) remains unknown due to the scarcity of reported cases. Herein we report a case of AML with t (6;21;8) (p23;q22;q22). Fluorescence in situ hybridization confirmed a RUNX1-RUNX1T1 fusion signal on the derivative chromosome 8. This is the first report on a variant of t (8;21) involving the breakpoint 6p23. After induction chemotherapy, our patient achieved complete remission and has been stable for four years.

[Klinefelter's syndrome diagnosed at the onset of acute myeloid leukemia with inv (16) following treatment for germ cell tumor].

A 22-year-old man with a history of mediastinal germ cell tumor, which was diagnosed at age 20 and remained disease-free after chemotherapy, was diagnosed with acute myeloid leukemia (AML) M2 in January 2020. Karyotype analysis of bone marrow (BM) specimen at diagnosis detected 47,XXY, inv (16) in all cells. Following induction treatment, he achieved complete remission with a remarkable decrease in the minimal residual disease marker. Although considered related to therapy, the AML had a prognostically favorable karyotype, and the initial treatment response was very good. He had no human leukocyte antigen-matched sibling donor candidate. Thus, allogeneic hematopoietic stem cell transplantation was not scheduled at the first complete remission. After three cycles of consolidation therapy, he remained disease-free for over one year. Karyotype analysis of BM during remission revealed that all analyzed cells harbored 47,XXY, and Klinefelter syndrome (KS) was diagnosed. Although the patient experienced an adjustment disorder on KS diagnosis, he had overcome the difficulty with the assistance of psycho-oncologists, clinical psychologists, and genetic counselors. Herein, we report this rare case of KS that manifested after AML diagnosis following mediastinal germ cell tumor treatment.

[Haploidentical hematopoietic stem cell transplantation for graft failure in myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable complicated with Stenotrophomonas maltophilia bacteremia].

A 60-year-old woman with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent unrelated bone marrow transplantation from a human leukocyte antigen (HLA) 8/8 allele-matched male donor. Neutrophil engraftment was achieved on day 29. Fluorescence in situ hybridization of sex chromosomes demonstrated complete donor chimerism. The red blood cell and platelet transfusion dependence continued, and the neutrophil count decreased gradually. Despite prolonged administration of broad-spectrum antibiotics for febrile neutropenia, blood cultures on days 46 and 58 returned positive for Stenotrophomonas maltophilia (SM). Contrast-enhanced computed tomography revealed multiple nodules of septic emboli in the lungs and kidneys, suggesting a disseminated SM infection. Antibiotic therapy was conducted based on antimicrobial susceptibility testing. However, the blood cell count failed to normalize and a secondary graft failure was diagnosed. A HLA-haploidentical peripheral-blood stem-cell transplantation from the patient's son was performed on day 134 after the initial transplantation. Neutrophil engraftment was achieved on day 11. Red blood cells and platelets were also engrafted. After the resolution of the SM bacteremia, the patient was discharged on day 63. The prognosis of the SM bacteremia with neutropenia is poor. Antibiotic treatment based on antimicrobial susceptibility testing and a second transplant from an HLA-haploidentical donor likely contributed to the successful outcome in this patient.

Successful Cord Blood Transplantation for Idiopathic CD4+ Lymphocytopenia.

Idiopathic CD4+ lymphocytopenia (ICL) is the depletion of CD4+ lymphocytes to <300 cells/mm3 without human immunodeficiency virus infection or other causes of lymphocytopenia. ICL causes fatal infections; its etiology remains unclear and it lacks consensus regarding therapeutic options. We report the first patient with ICL who had a successful clinical course following a cord blood transplant (CBT). A 45-year-old woman was diagnosed with ICL and underwent partial hepatectomy for an abscess caused by the Mycobacterium avium complex. No specific gene alterations were detected through next generation sequencing-based evaluation. Following a reduced-intensity conditioning (RIC) regimen consisting of fludarabine, busulfan, and 4 Gy total body irradiation, a single-unit CBT was performed. Neutrophils were engrafted on day +14. CD4+ lymphocyte counts increased to over 300 cells/mm3 on day +436. After 75 months, she was alive without any sequelae. CBT with an RIC regimen could be a curable treatment option for ICL.

[Clinical features of tuberculosis among allogeneic hematopoietic stem cell transplantation recipients].

The incidence of tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is 10-40 times higher than that in the general population, which ranges from 0.1% to 5.5%. However, the clinical features of TB among allo-HSCT recipients in Japan remain unknown. We retrospectively analyzed the incidence of TB and the clinical features of culture-positive TB among allo-HSCT recipients at our hospital between 2002 and 2018. Of 1,047 recipients, 5 (0.4%) developed pulmonary TB (with an incidence rate of 472 per 100,000 population) at a median of 1,730 (range: 586-2,526) days after allo-HSCT. Three patients had chronic graft-versus-host disease upon the onset of TB, which was well-controlled with tacrolimus and/or steroid. Three of five patients completed TB treatment, and the disease did not flare up after therapy completion. The incidence of TB was higher in allo-HSCT recipients than in the general population (0.01%, with an incidence rate of 12.3 per 100,000 population). Therefore, TB should be considered a late complication among allo-HSCT recipients.

Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment-free remission.

This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D-STOP, after a 3-year follow-up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Estimated treatment-free remission (TFR) rates at 12 and 36 months were 63.0% [95% confidence interval (CI): 48.7-74.3] and 59.3% (95% CI: 45.0-71.0), respectively. CD3- CD56+ NK, CD16+ CD56+ NK, and CD57+ CD56+ NK large granular lymphocyte (NK-LGL), CD8+ CD4- cytotoxic T cell, and CD57+ CD3+ T-LGL cell numbers were relatively elevated throughout the 24-month consolidation only in failed patients who molecularly relapsed within 12 months. In successful patients, these subsets elevated transiently after 12 months, but returned to basal levels after 24-month consolidation. Therefore, smaller changes in NK/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3- CD56+ NK >376 cells/µL, CD16+ CD56+ NK > 241 cells/µL, or CD57+ CD56+ NK-LGL >242 cells/µL during consolidation compared with others were 26.7% (8.3%-49.6%) vs 78.3% (55.4%-90.3%), HR 0.032 (0.0027-0.38; P = .0064), 31.2% (11.4%-53.6%) vs 85.0% (60.4%-94.9%), HR 0.039 (0.0031-0.48; P = .011), or 36.8% (16.5%-57.5%) vs 77.3% (53.7%-89.8%), HR 0.21 (0.065-0.69; P = .010), respectively. Therefore, silent responses of T/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D-STOP, NCT01627132).

Geriatric nutritional risk index as a useful prognostic factor in second allogeneic hematopoietic stem cell transplantation.

Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2 years after second allo-HSCT: 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2 years after second allo-HSCT decreased according to the score: 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P < 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.

Bone turnover markers as an aid to monitor osteoporosis following allogeneic hematopoietic stem cell transplantation.

Bone turnover markers (BTMs) are useful parameters for assessing fracture risk and unlike bone mineral density (BMD), can be measured at any institution. However, BTM values have not been established in patients post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the practicality of BTMs in patients who underwent allo-HSCT by measuring levels of the serum bone resorption marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation marker, bone-specific alkaline phosphatase (BAP), together with BMD, 1 month before and 6 months after allo-HSCT. Patients were classified into either the alendronate group (n = 14) if alendronate treatment (35 mg orally per week) was administered before allo-HSCT or within 1 month after allo-HSCT, or the control group (n = 16), in which patients did not receive alendronate treatment. Despite the high frequency of corticosteroids users in the alendronate group (71.4 vs. 18.9%; p < 0.01), the mean percentage changes in BMD at the lumbar spine (- 2.9 vs. - 3.1%; p = 0.44) and femoral neck (- 3.2 vs. - 4.1%; p = 1.00), TRACP-5b levels (- 4.8 vs. 9.9%; p = 0.45), and BAP levels (6.9 vs. 1.0%; p = 0.85) during 6 months did not differ significantly between the alendronate and control groups. Additionally, the percentage changes in BMD at the lumbar spine were negatively associated with the TRACP-5b levels 6 months after allo-HSCT (p = 0.03, r = 0.40). Our results indicate the possible effectiveness of alendronate treatment in allo-HSCT patients. BTM levels could be useful to monitor the BMD changes.

Unmanipulated haploidentical hematopoietic stem cell transplantation using very low-dose antithymocyte globulin and methylprednisolone in adults with relapsed/refractory acute leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) could be the only curative therapy for patients with relapsed/refractory acute leukemia (RRAL). Many reports have described unmanipulated haploidentical HSCT (HID-HSCT) using high-dose antithymocyte globulin (ATG). However, the transplant outcomes of HID-HSCT using very low-dose ATG (thymoglobulin, 2-2.5 mg/kg) and methylprednisolone (mPSL, 1 mg/kg) for patients with RRAL have not been reported. We compared the outcomes of 46 patients with RRAL who underwent HID-HSCT using very low-dose ATG (thymoglobulin) and mPSL with the outcomes of 72 patients who underwent non-HID-HSCT. Patient characteristics differed regarding conditioning intensity (myeloablative; 19.6% in HID-HSCT vs. 61.1% in non-HID-HSCT, P < 0.001) and having undergone multiple HSCT (26.1% vs. 11.1%, P = 0.045). However, we found no significant differences in the 1-year overall survival (OS, 31.7% vs. 29.1%; P = 0.25), disease-free survival (DFS, 20.5% vs. 23.7%; P = 0.23), cumulative incidence of relapse (CIR, 40.0% vs. 42.8%; P = 0.92), non-relapse mortality (NRM, 39.5% vs. 33.5%; P = 0.22), or 100-day grade II-IV acute graft-versus-host disease (32.6% vs. 34.7%; P = 0.64) following HID-HSCT vs. non-HID-HSCT, respectively. Subgroup analysis stratified by disease and intensity of conditioning regimen demonstrated the same results between HID-HSCT and non-HID-HSCT. Furthermore, multivariate analysis showed that HID-HSCT was not an independent prognostic factor for OS (hazard ratio (HR) = 0.95 [95% confidence interval (CI), 0.58-1.58]), DFS (HR = 1.05 [95%CI, 0.67-1.68]), CIR (HR = 0.84 [95%CI, 0.48-1.47]), or NRM (HR = 1.28 [95%CI, 0.66-2.46]). In summary, transplant outcomes for RRAL were comparable in the HID-HSCT and non-HID-HSCT groups. HID-HSCT using very low-dose ATG and mPSL for RRAL may be a viable alternative to non-HID-HSCT.

[Vacuolar myelopathy after allogeneic bone marrow transplantation in a patient with acute lymphoblastic leukemia].

Vacuolar myelopathy (VM) is known to be a neurological complication in patients with acquired immunodeficiency syndrome (AIDS). In autopsy-based studies, VM was reported in approximately 20-50% of patients with AIDS. It manifests in various says, mainly presenting as a painless spastic paraparesis with a sensory ataxia. We present a rare case of VM after bone marrow transplantation (BMT) in a patient without AIDS. A 50-year-old man developed weakness in the lower legs, leg muscle atrophy, and difficulty in walking 86 days after BMT. The patient died from septic shock on day 309. The autopsy revealed intralamellar vacuolation in the spinal white matter, which was compatible with VM.

[Tyrosine kinase inhibitor maintenance therapy following allogenic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia].

There have been many reports regarding tyrosine kinase inhibitor (TKI) administration to prevent relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, there are no commonly accepted standards for the choice of TKIs. We retrospectively analyzed the clinical features of Ph+ALL patients who received TKIs after allo-HSCT at our institution. The prophylactic administration of TKIs (pro) occurred in eight patients, and six patients received preemptive TKI administration (pre). The median follow-up period after allo-HSCT was 1,427 (range, 161-2,428) days in the pro group and 773.5 (range, 156-2,243) days in the pre group. Only one patient with non-hematological complete remission before allo-HSCT relapsed among the patients in the pro group. In the pre group, four patients treated with only TKIs achieved negativity of minimal residual disease. The 2-year overall survival rate after allo-HSCT was 85.7% in the pro group and 100% in the pre group. We used lower doses of TKIs compared with previous reports and this analysis shows that the dose is safe and effective as the treatment.

Reassessment of clinical implication of pretransplant surgical procedures for pulmonary invasive fungal lesions.

Dealing with the recent series of allogeneic hematopoietic stem cell transplantation (allo-SCT) performed this decade, we reassessed the clinical impact of pretransplant surgical procedures (SP) for pulmonary lesions of invasive fungal disease (IFD) on subsequent transplant outcome. We focused on the clinical outcomes of seven patients with pulmonary IFD who underwent segmentectomy (n = 4), lobectomy (n = 2) or abscess incision with drainage only (n = 1), and compared results to those of 21 patients carrying pulmonary IFD who never underwent invasive SP before allo-SCT. The rate of exacerbation of pulmonary lesions by 180 days after allo-SCT did not differ significantly between groups (32.2% vs 42.9%, P = 0.69). Moreover, no significant differences in non-relapse mortality (46.4% vs 42.3%, P = 0.93) or overall survival (53.6% vs 30.9%, P = 0.45) at 1 year were evident between groups. These results indicate that pretransplant SP for pulmonary lesions might have no survival benefit under the current antifungal prophylaxis or treatment modality.

Disseminated adenovirus infection in a patient with relapsed refractory multiple myeloma undergoing autologous stem cell transplantation and pomalidomide/dexamethasone as salvage regimens.

BACKGROUND: Disseminated adenovirus (ADV) infection is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, it is rare following autologous peripheral blood stem cell transplantation (auto-PBSCT) or chemotherapy alone. CASE: A 66-year-old Japanese female with relapsed and refractory multiple myeloma (RRMM) received auto-PBSCT, achieving partial response. To obtain a greater response, pomalidomide/dexamethasone was started on day 28 after auto-PBSCT, but was stopped on day 41 due to thrombocytopenia, fever, and gross hematuria. Additionally, she complained of abdominal pain on day 46. Blood tests revealed elevation of transaminases and alkaline phosphatase. There was no evidence of bacterial or fungal infections or progression of MM. ADV titer in urine and serum were 3.41 × 105 copies/mL and 6.76 × 103 copies/mL, respectively. CT scans revealed cystitis, urethritis, and peritonitis. Since more than two organs were infected with ADV, she was diagnosed with disseminated ADV disease. After 5 weeks of supportive care, all symptoms resolved. ADV titer decreased to 5.90 × 102 copies/mL in urine and became negative in serum on day 80. However, she succumbed to the MM a little more than a month later. CONCLUSION: Disseminated ADV infection can occur even in non-allogeneic transplant settings, such as in severely immunocompromised patients with MM who receive auto-PBSCT and repeated salvage therapies. Although it is a rare event, the mortality rate of this disease is very high, and hence, early diagnosis and interventions are needed in suspected cases.

[Transfusion-associated circulatory overload with pulmonary alveolar hemorrhage following allogeneic bone marrow transplantation].

A 51-year-old man underwent allogeneic bone marrow transplantation (BMT) for recurrent acute myeloid leukemia. Although the patient developed slight edema, pleural effusion, and cardiac effusion 6 months after BMT, his clinical condition improved with furosemide treatment. The patient was transfused with red blood cells for the management of anemia 8 months after BMT. He developed acute respiratory failure with pulmonary alveolar hemorrhage 80 min after the transfusion. He was diagnosed with transfusion-associated circulatory overload (TACO) due to the presence of acute pulmonary congestion and depressed left ventricular systolic function. Reduced circulatory load due to sufficient furosemide led to ventilator weaning 3 days later. Other causes of pulmonary alveolar hemorrhage were excluded, and the patient's condition improved by cardiac failure treatment only. This clinical course indicated that pulmonary alveolar hemorrhage would breakdown the blood vessels due to acute pulmonary congestion. Chemotherapy and prolonged anemia are high risks for cardiac failure in patients with hematological malignancies. Therefore, the possibility of cardiac failure is considered when patients with hematological malignancies have fluid retention, such as cardiac enlargement, edema, and pleural effusion. Moreover, the body fluids should be monitored before and after blood transfusion.

Dasatinib cessation after deep molecular response exceeding 2 years and natural killer cell transition during dasatinib consolidation.

Tyrosine kinase inhibitors (TKI) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMR); some patients have successfully discontinued TKI therapy after maintaining DMR for ≥1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for ≥2 years. This study included 54 patients with CML who were enrolled in a D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation. Peripheral lymphocyte profiles were analyzed by flow cytometry. The estimated 12-month treatment-free survival (TFS) was 62.9% (95% confidence interval: 48.5%-74.2%). During dasatinib consolidation, the percentage of total lymphocytes and numbers of CD3- CD56+ natural killer (NK) cells, CD16+ CD56+ NK cells and CD56+ CD57+ NK-large granular lymphocytes (LGL) were significantly higher in patients with molecular relapse after discontinuation but remained unchanged in patients without molecular relapse for >7 months. At the end of consolidation, patients whose total lymphocytes comprised <41% CD3- CD56+ NK cells, <35% CD16+ CD56+ NK cells, or <27% CD56+ CD57+ NK-LGL cells had higher TFS relative to other patients (77% vs 18%; P < .0008; 76% vs 10%; P < .0001; 84% vs 46%; P = .0059, respectively). The increase in the number of these NK cells occurred only during dasatinib consolidation. In patients with DMR, dasatinib discontinuation after 2-year consolidation can lead to high TFS. This outcome depends significantly on a smaller increase in NK cells during dasatinib consolidation.

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201.

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5-25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.

Reduced therapeutic effect of antiviral drugs in patients with hepatitis B virus reactivation after hematopoietic stem cell transplantation.

AIM: Patients with resolved hepatitis B virus (HBV) infection following hematopoietic stem cell transplantation (HSCT) are potentially at high risk of HBV reactivation. Although antiviral drug therapy is recommended when HBV DNA reappears in the serum, drug efficacy after HBV reactivation remains unclear. METHODS: Host immune response against HBV was investigated by immunological analyses at 12 months after entecavir (ETV) treatment in six HSCT-treated and five non-HSCT-treated patients with HBV reactivation, and 18 patients with chronic hepatitis B (CHB). Peripheral HBV-specific CD8+ T cells were analyzed for total numbers by flow cytometry and tetramer staining, as was intracellular γ-interferon (IFN-γ) production and CD107a expression in response to HBV peptides. Interleukin-10 (IL-10)-expressing CD19+ B-cell count and serum inflammatory cytokine levels were also analyzed. RESULTS: Serum HBV DNA was detectable in HSCT-treated patients with HBV reactivation at 12 months compared with other groups, indicating insufficient ETV efficacy against HBV. The HBV-specific CD8+ T-cell counts in HSCT-treated patients with HBV reactivation were significantly lower compared with those in non-HSCT patients. Additionally, IFN-γ production and CD107a expression by CD8+ T cells after incubation with HBV peptides was significantly reduced in HSCT-treated compared with CHB patients at 12 months after ETV treatment. Conversely, HSCT-treated patient serum IL-10 levels were significantly elevated compared with those in non-HSCT patients. Finally, IL-10-producing CD19+ B-cell counts were increased in HSCT-treated compared with CHB patients. CONCLUSION: After HBV reactivation, ETV efficacy was impaired in HSCT-treated patients as evidenced by low HBV-specific CD8+ T-cell counts and high B-cell IL-10 production.