Effects of combined test dose and therapeutic drug monitoring strategy in exposure-directed busulfan.

Although exposure-directed busulfan (BU) dosing can improve allogeneic hematopoietic stem cell transplantation outcomes, there is still large variability in BU exposure with test dose alone due to changes in BU clearance caused by drug interactions. We conducted a single-arm phase II trial using the combined test dose and therapeutic drug monitoring strategy (PK-guided group) and compared the outcomes with an external historical cohort receiving a fixed-dose (fixed-dose group). The first eight and second eight doses were adjusted based on the area under the blood concentration-time curve (AUC) of the test and first doses, respectively, targeting a total AUC of 82.1 mg·h/L. All patients received either BU and cyclophosphamide conditioning (BU/CY) or fludarabine (FLU)-containing conditioning. The BU clearance at the first dose decreased more in patients receiving FLU than in those receiving BU/CY; however, BU clearance also declined over time in patients who received BU/CY. The simulated total AUC (sAUC) with test dose only was significantly higher in patients who received FLU than in those who received BU/CY, but sAUC with the combined strategy was comparable. The 100-day progression-free survival was 85.5% (95% confidence interval [CI]: 71.9-92.8%), and was not inferior to that in the fixed-dose group. For the FLU-containing regimens, the PK-guided group showed decreased relapse (0.0% vs. 26.9%, p = 0.03), and favorable overall survival (75.1% vs. 57.0%, p = 0.07) at 1 year. The combined strategy effectively controlled the BU exposure close to the target levels, potentially improving efficacy, especially in patients receiving the FLU-containing regimen. Clinical evaluation of efficacy of dose-modified intravenous busulfan in allogeneic hematopoietic stem cell transplantation for hematological malignancy (#UMIN000014077, June 15th, 2014).

[HIV-negative plasmablastic lymphoma sustaining long-term response after autologous peripheral blood stem cell transplantation].

The patient is a 34-year-old HIV antibody-negative female with normal immunocompetence. The patient was referred to the hospital of the current study due to diarrhea and abdominal pain, which developed in May 2014. On conducting computed tomography (CT), remarkable wall thickening was noted in the terminal ilium over the ascending colon, suggesting a malignant tumor. However, making a definite diagnosis by lower gastrointestinal endoscopic biopsy and left hemicolectomy was not possible. The dense proliferation of plasma cell-like cells and plasmablasts was noted; CD20, CD19, CD79a, CD3, CD4, and Epstein-Barr virus-encoded miRNAs (EBER) were negative and CD138 was positive on immunostaining. Based on the aforementioned data, the patient was diagnosed with plasmablastic lymphoma (PBL). High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (PBSCT) was performed in the first remission period after the completion of four cycles of hyper CVAD/MTX-AraC alternating therapy. Remission was confirmed by FDG-PET/CT 3 months after autologous PBSCT. No signs of recurrence have been observed in 6 years after the transplantation. Although no standard treatment for PBL has been established, autologous peripheral blood stem cell transplantation combined with high-dose chemotherapy during the first remission period may be a beneficial treatment option.

[Treatment for acute leukemia showing PCR-positivity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at initial diagnosis: a case report and review of literature].

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world. We encountered two patients with COVID-19 who underwent treatment for acute leukemia at initial diagnosis. Both the patients received conventional induction therapy without the exacerbation of COVID-19. Although the impact of SARS-CoV-2 on the treatment of leukemia is unclear, our treatment experience suggests that there is no major contraindication to standard chemotherapy for acute leukemia in patients with COVID-19. As COVID-19 continues to be a threat worldwide, further evaluations of large cohorts are needed for future treatment decisions for acute leukemia with COVID-19.

Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation for Mature T Cell and Natural Killer Cell Neoplasms in the Kyoto Stem Cell Transplantation Group.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the key strategy to cure patients with mature T and natural killer (NK) cell lymphomas/leukemia, especially those with relapsed/refractory diseases, there is no consensus strategy for donor selection. We retrospectively analyzed the outcomes of allo-HSCT in 111 patients in 15 Japanese institutions as a multi-institutional joint research project. Thirty-nine patients received bone marrow or peripheral blood stem cell transplantation from related donors (rBMT/rPBSCT), 37 received BMT/PBSCT from unrelated donors (uBMT/uPBSCT), and 35 received cord blood transplantation (CBT). Overall survival (OS) and progression-free survival (PFS) at 4 years were 42% and 34%, respectively. The cumulative incidences of relapse and nonrelapse mortality were 43% and 25%. In multivariate analysis, CBT showed comparable OS with rBMT/rPBSCT (rBMT/rPBSCT versus CBT: hazard ratio [HR], 1.63; P = .264) and better OS compared with uBMT/uPBSCT (HR, 2.99; P = .010), with a trend toward a lower relapse rate (rBMT/rPBSCT versus CBT: HR, 2.60; P = .010; uBMT/uPBSCT versus CBT: HR, 2.05; P = .082). This superiority of CBT was more definite in on-disease patients (OS: rBMT/rPBSCT versus CBT: HR, 5.52; P = .021; uBMT/uPBSCT versus CBT: HR, 6.80; P = .007). Better disease control was also strongly associated with better OS and PFS with lower relapse rate. In conclusion, allo-HSCT is beneficial for the survival of patients with mature T and NK cell lymphomas/leukemia if performed in a timely fashion. Since CBT showed favorable survival with a lower relapse risk, it could be a preferred alternative, especially in on-disease patients.

Outcomes of allogeneic stem cell transplantation for DLBCL: a multi-center study from the Kyoto Stem Cell Transplantation Group.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) has been considered as a potentially curative treatment option for refractory or relapsed diffuse large B cell lymphoma (DLBCL) patients. However, there is little information available, especially for Japanese patients and in cord blood transplantation (CBT). We aimed to determine treatment outcomes of allo-SCT for DLBCL in the Kyoto Stem Cell Transplantation Group, a multi-institutional joint research group. Sixty-eight DLBCL patients who underwent their first allo-SCT between 2003 and 2016 were included. The median time from diagnosis to transplantation was 13.5 months. Thirty-one patients were in CR/PR at transplantation. Twenty-seven patients underwent CBT. The median follow-up for survivors was 44.2 months. Four-year overall survival (OS) and relapse-free survival (RFS) rates were 23% (95% CI, 13-35%) and 20% (95% CI, 11-31%), respectively. Cumulative incidences of non-relapse mortality and relapse were 23% and 57%, respectively. Patients in CR/PR at allo-SCT had better OS (4-year, 46% vs 4%, P < 0.001) and RFS (4-year, 36% vs 7%, P = 0.005). The source of the stem cell did not significantly affect OS (4-year, bone marrow vs cord blood vs peripheral blood, 28.6% vs 27.2% vs 6.5%, P = 0.193). In multivariate analysis, non-remission status at SCT associated with inferior OS and RFS. Duration from diagnosis to transplantation of less than 1 year associated with inferior RFS. Allo-SCT, including CBT, may be a promising therapeutic modality for DLBCL patients who have good disease control at transplantation.

Rapidly progressive hemorrhagic pneumonia caused by Stenotrophomonas maltophilia occurring early after bone marrow transplantation in a patient with myelodysplastic syndrome.

A 44-year-old woman had repeated bacterial infections because of hypoplastic myelodysplastic syndrome; therefore, she underwent allogeneic hematopoietic cell transplantation. Broad spectrum antibiotics were administered because she had bacterial infection and pneumonia 2 weeks before undergoing transplantation. On day19 after transplantation, she suddenly presented with hemoptysis. Stenotrophomonas maltophilia was considered to be the cause of hemorrhagic pneumonia, which required ventilation support, massive transfusion, and catecholamine administration. However, she died 8 h after the onset of hemoptysis. Severe S. maltophilia infections may occur in patients with immunocompromised conditions such as those after allogeneic hematopoietic cell transplantation.

Clinical and echocardiographic characteristics for differentiating between transthyretin-related and light-chain cardiac amyloidoses.

Differential diagnosis between transthyretin (TTR) and immunoglobulin light-chain (AL) cardiac amyloidoses is essential due to significantly different prognoses and therapeutic options. Therefore, clinical characteristics of patients with biopsy-proven cardiac amyloidosis were investigated to differentiate TTR from AL amyloidosis. From September 2006 to May 2014, 46 patients were confirmed to have cardiac amyloidosis (TTR, n = 28; AL, n = 18) in our institute. The median age of patients with TTR amyloidosis was 78 years (range 61-90) with 27 (96 %) males, while that of patients with AL amyloidosis was 66 (range 52-76) with 12 (67 %) males. There were no statistically significant differences in echocardiographic findings regarding left ventricular (LV) systolic function or diastolic dysfunction between the two groups. Interestingly, serum brain natriuretic peptide (BNP) levels in patients with AL amyloidosis were significantly higher than those in TTR amyloidosis patients. In contrast, the LV wall was significantly thicker in patients with TTR amyloidosis than in those with AL amyloidosis. Therefore, the ratio of BNP to LV mass index (LVMI) at presentation in AL amyloidosis patients was significantly higher than that in TTR patients (6.7 vs 2.9, p = 0.0006). A BNP-LVMI ratio of less than 3.5 had a diagnostic sensitivity and specificity for TTR amyloidosis of 71 and 83 %, respectively. One-year overall survival was 88.7 % in the patients with TTR amyloidosis and 23.7 % in the patients with AL amyloidosis. Our analysis indicates that the BNP-LVMI ratio, as well as age and sex, may be useful parameters for distinguishing TTR from AL cardiac amyloidosis.

[Infliximab therapy for Crohn's-like gastrointestinal lesions after allogeneic bone marrow transplantation].

A 45-year-old man was diagnosed with t(8;21) positive acute myelogenous leukemia and failed to achieve complete remission (CR) after the first induction chemotherapy. He was then treated with high-dose cytarabine and achieved CR. Molecular relapse was detected during post-remission therapy and he underwent myeloablative bone marrow transplantation from his HLA-matched sibling donor. One year after transplantation, he developed an intractable anal fistula during treatment of chronic GVHD. Colonoscopy showed longitudinal ulcers and cobblestone appearance, and histopathological examination revealed non-caseating epithelioid granuloma. According to these findings, he was diagnosed with Crohn's-like chronic gastrointestinal inflammatory disease. He was treated with enteral nutrition, mesalazine and dose re-escalation of cyclosporine, but these therapies were not effective. Therefore, we decided to treat him with infliximab. After starting treatment with infliximab, his abdominal symptoms and the anal fistula showed prompt improvement. There are few reports regarding the efficacy of infliximab for gastrointestinal chronic GVHD. Our experience suggests that infliximab could be useful for the treatment of Crohn's-like gastrointestinal inflammatory disease.

[Successful second cord blood transplantation (CBT) for late graft failure associated with several immune disorders after the initial CBT in a patient with acute myeloid leukemia].

A 64-year-old woman underwent reduced-intensity conditioning cord blood transplantation (RIC-CBT) for refractory acute myeloid leukemia (AML). A 6/6 antigen-level HLA-identical cord blood from a male infant was transfused. After successful engraftment with complete donor chimerism, the patient developed mixed chimera (XX 8.8%) on day 82. Tapering of tacrolimus was started on day 96. Bone marrow chimerism analysis showed a decreasing recipient cell population (XX 2.2%) on day 117 and tacrolimus was discontinued with no clinical signs of GVHD on day 123. However, pancytopenia with agranulocytosis was detected on day 138. She was diagnosed as having secondary graft failure associated with Coombs-positive immune hemolytic anemia and immune thrombocytopenia (ITP). At the same time, the percentage of recipient T cell chimerism in peripheral blood was about 50% and the B cell population showed lambda light chain restriction. On day 180, she received a second RIC-CBT due to lack of improvement of agranulocytosis. A single dose of rituximab was administered on day - 11 before the second CBT to eliminate the activated B cells. Prompt neutrophil engraftment was achieved and both hemolytic anemia and ITP also showed resolution. She is currently well (30 months after the second CBT), showing normal blood cell counts and complete second donor chimerism of marrow cells.

[Extranodal natural killer/T-cell lymphoma, nasal type developing central nervous system and epididymis involvement immediately after concurrent chemoradiotherapy].

A 66-year-old man showed central nervous system (CNS) and epididymis involvement after concurrent chemoradiotherapy for extranodal natural killer/T-cell lymphoma, nasal type (ENKL). The patient experienced continuous nasal obstruction. CT revealed a mass in the nasal cavity and paranasal sinuses. Biopsy of the nasal cavity mass showed it to be ENKL. Based on bone marrow biopsy and 18F-FDG PET/CT findings, the clinical stage was suspected to be IIE. The sites involved were the nasal cavity, paranasal sinuses, and cervical lymph nodes. We performed concurrent chemoradiotherapy consisting of a 67% dose of DeVIC and involved field radiation therapy towards his head and neck. Head and neck CT confirmed a therapeutic response. After receiving concurrent chemoradiotherapy, the patient complained of perineal discomfort. Ultrasonography revealed swelling of the left epididymis. Left epididymis biopsy showed ENKL involvement and lumbar puncture revealed CNS involvement. The findings of this case suggest that evaluation of CNS involvement might be an essential part of the initial workup for some ENKL patients.

Direct hemoperfusion using polymyxin-B immobilized fiber for severe septic patients with hematological disorders: a single-center analysis.

The benefit of endotoxin absorption therapy (direct hemoperfusion with polymyxin B-immobilized fiber: PMX-DHP) for severe septic patients is still controversial. There are limited data on the clinical experience and efficacy of PMX-DHP for septic patients with hematological disorders. At our institution, 16 patients with hematological diseases underwent PMX-DHP therapy for gram-negative septic shock from February 2006 to March 2012. Most of the patients had severe neutropenia (median neutrophil counts: 7/µL) due to intensive chemotherapy for their hematological diseases. After the PMX-DHP therapy, six patients recovered from the shock status (favorable group) and ten died of the sepsis (unfavorable group). We analyzed the differences between the two groups based on clinical characteristics just before PMX-DHP therapy. Regarding sequential organ failure assessment (SOFA) score, which is a scoring system to determine the degree of organ dysfunction, all patients in the favorable group scored less than 11. The sensitivity and specificity of SOFA score less than 11 for the therapeutic efficacy were 100% and 80%, respectively. Our results suggest that septic patients with hematological diseases may not be a candidate for PMX-DHP therapy when they have already developed serious organ dysfunction.

Long-term survival of a patient with multiple myeloma-associated severe cardiac AL amyloidosis after implantation of a cardioverter-defibrillator.

Cardiac involvement is by far the most relevant factor impacting poor outcomes of patients with systemic light-chain (AL) amyloidosis. Median survival of patients with symptomatic cardiac AL amyloidosis is less than 6 months. Approximately two-thirds of these patients die suddenly due to ventricular arrhythmias and electromechanical dissociation. We report a 56-year-old female with very severe cardiac AL amyloidosis (NT-proBNP 13,355 ng/l, troponin T 0.16 µg/l, and systolic blood pressure 100 mmHg), who was successfully treated with diuretics and an implantable cardioverter-defibrillator (ICD) and has survived for more than 4 years, to date. During the 4-year period after receiving the ICD, she experienced several episodes of sustained ventricular tachycardia and ventricular fibrillation, all successfully terminated by anti-tachycardia pacing or electrical shock. The benefit of ICD for cardiac AL amyloidosis is unclear since there have been only a few reports of successful use of this therapy for patients with cardiac AL amyloidosis. Recently, new treatment options for AL amyloidosis, such as bortezomib and lenalidomide, have shown high response rates and improved outcomes. It is important to identify those cardiac amyloidosis patients who might be more likely to benefit from ICD implantation.

[A case of cytomegalovirus gastroduodenitis in an immunocompetent adult].

A 58-year-old male developed epigastric discomfort and high fever in 2010. Complete blood count showed leukocytosis and a small number of atypical lymphocytes. Gastric endoscopy revealed multiple gastroduodenal erosions and ulcers. Biopsy specimens were obtained and pathological examination demonstrated cytomegalic inclusion bodies. Cytomegalovirus (CMV) IgM antibody was positive and CMV DNA was detected with PCR in his blood, leading to the diagnosis of CMV gastroduodenitis. He was treated with intravenous ganciclovir and his symptoms resolved rapidly. It is recognized that CMV gastroduodenitis is extremely rare in immunocompetent hosts but sometimes shows a severe clinical course in elderly patients. The results from our present patient suggest that we should consider CMV infection in the differential diagnosis of multiple gastroduodenal erosions and ulcers. Our data also suggested that anti-CMV medications could be important treatment options for CMV gastroduodenitis, especially in elderly patients.

[Streptococcal toxic shock-like syndrome caused by Streptococcus dysgalactiae subsp. equisimilis in a patient with acute myeloid leukemia at diagnosis].

A 46-year-old woman was urgently admitted to our hospital due to acute renal failure, liver dysfunction, disseminated intravascular coagulation, shock status, and impaired consciousness. About 1 day prior to admission, she developed a high-grade fever, bilateral lower leg pain, and multiple small papules. She was diagnosed with streptococcal toxic shock syndrome (STSS) caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE) associated with acute myeloid leukemia. The emm gene type of the isolated SDSE was shown to be stG2078. Her invasive streptococcal infection resolved with immediate administration of meropenem and continuous hemodiafiltration. However, she died of septic shock caused by multidrug-resistant Pseudomonas aeruginosa one month after admission. Recently, epidemiological studies have shown increasing numbers of invasive SDSE infections, including STSS and necrotizing fasciitis, often among immunocompromised patients. This suggests that hematologists as well as primary care doctors need to be aware of the possibility of the invasive infections caused by SDSE. An influenza-like illness consisting of a fever, lower extremity pain, and diarrhea are common initial symptoms in STSS patients. Awareness of these prodromal symptoms could lead to the early diagnosis of the illness and prompt initiation of antibiotic treatment.

The efficacy and safety of caplacizumab in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura: an open-label phase 2/3 study.

Caplacizumab is an anti-von Willebrand factor humanized single-variable-domain immunoglobulin fragment whose efficacy and safety in immune-mediated thrombotic thrombocytopenia purpura (iTTP) have been demonstrated in international studies. This prospective, open-label phase 2/3 study evaluated caplacizumab 10 mg administered daily during plasma exchange and for 30 days afterward, in combination with immunosuppressive treatment, in Japanese adults with a clinical diagnosis of iTTP (new or recurrent). The primary endpoint was prevention of iTTP recurrence; key secondary endpoints included time to platelet count response, time to organ damage normalization, and safety. Among 21 treated patients, 1 of 15 (6.7%) evaluable patients developed iTTP recurrence. Median time to normalization was 2.79 days for platelet count and 2.65 days for organ damage markers (n = 15). Treatment-emergent adverse events (TEAEs) were mostly mild to moderate in severity; the most frequently reported caplacizumab-related TEAEs were increased alanine aminotransferase, epistaxis, and gastrointestinal hemorrhage (all in 9.5% of patients). At least one bleeding event was reported in 7 of 21 patients (33%). Caplacizumab was effective in Japanese patients with iTTP, with a low rate of iTTP recurrence, rapid normalization of platelet counts and organ damage markers, and no unexpected TEAEs. Trial registration: ClinicalTrials.gov identifier, NCT04074187.

Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation.

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.

Epitope Mismatch at HLA-DRB1 Associates with Reduced Relapse Risk in Cord Blood Transplantation for Standard-Risk Hematologic Malignancy.

Cord blood transplantation (CBT) is an attractive therapeutic option for patients with hematologic malignancies. CBT tolerates HLA mismatches between donors and recipients, but the HLA mismatches that generate graft-versus-tumor (GVT) effects remain unknown. Given that HLA molecules contain epitopes comprising polymorphic amino acids that determine their immunogenicity, we investigated associations between epitope-level HLA mismatches and relapse following single-unit CBT. A total of 492 patients with hematologic malignancies who underwent single-unit, T cell-replete CBT were included in this multicenter retrospective study. HLA epitope mismatches (EMs) were quantified using HLA matchmaker software from donor and recipient HLA-A, -B, -C, and -DRB1 allele data. Patients were dichotomized by median EM value and divided into 2 groups: patients who underwent transplantation in complete/partial remission (standard stage: 62.4%) and others (advanced stage: 37.6%). The median number of EMs in the graft-versus-host direction (GVH-EM) was 3 (range, 0 to 16) at HLA class I and 1 (range, 0 to 7) at HLA-DRB1. Higher HLA class I GVH-EM was associated with increased nonrelapse mortality (NRM) in the advanced stage group (adjusted hazard ratio [HR], 2.12; P = .021), with no significant advantage for relapse in either stage. In contrast, higher HLA-DRB1 GVH-EM was associated with better disease-free survival in the standard stage group (adjusted HR, .63; P = .020), which was attributed to lower relapse risk (adjusted HR, .46; P = .014). These associations also were observed even within HLA-DRB1 allele-mismatched transplantations in the standard stage group, indicating that EM might have an impact on relapse risk independent of allele mismatch. High HLA-DRB1 GVH-EM did not increase NRM in either stage. High HLA-DRB1 GVH-EM may lead to potent GVT effects and a favorable prognosis following CBT, especially in patients who underwent transplantation at the standard stage. This approach may facilitate appropriate unit selection and improve the overall prognosis of patients with hematologic malignancies who undergo CBT.

[Lethal pulmonary hemorrhage caused by Stenotrophomonas maltophilia pneumonia in a patient with acute myeloid leukemia].

A 63-year-old man had been treated with intensive chemotherapy for acute myeloid leukemia. On the 49th hospital day, he had febrile neutropenia after the second course of induction chemotherapy. On the 53 rd hospital day, he presented with hemoptysis and developed acute respiratory failure requiring ventilator support within several hours. On the 54th hospital day, the patient died with hemorrhagic respiratory infection. Stenotrophomonas maltophilia was detected in bacterial cultures of his blood, bronchoalveolar lavage, and sputum. To our knowledge, nine cases of fatal hemorrhagic pneumonia caused by S. maltophilia have been reported in the literature. All the patients had hematological neoplasms and were severely neutropenic after one or two intensive chemotherapy regimens. They died shortly (within 3 days) after the onset of the hemorrhagic pneumonia. Management of the infection caused by S. maltophilia is hampered by high-level intrinsic resistance to multiple antibiotics and the increasing occurrence of acquired resistance to co-trimoxazole and fluoroquinolones. It would be important to keep in mind that hemorrhagic respiratory infection caused by S. maltophilia may lead to a fulminant and lethal course in severely neutropenic patients with hematological neoplasms and to recognize which antibiotic agents are more sensitive to S. maltophilia in each institution.