Human herpesvirus 6 encephalitis in patients administered mycophenolate mofetil as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. METHODS AND RESULTS: We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. CONCLUSIONS: Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

Loss of CD45 expression at relapse of acute myeloid leukemia.

A 49-year-old female was initially diagnosed with acute myeloid leukemia (AML) M4 with a CD45＋CD13＋CD33＋CD34-HLA-DR＋ immunophenotype. She underwent allogeneic bone marrow transplantation, but the disease recurred. The bone marrow was infiltrated with 87.0% blasts negative for myeloperoxidase (MPO) staining. Immunophenotyping by flow cytometry identified the presence of a CD45-negative blast population. These blasts exhibited a CD13＋CD33＋CD19-CD10-CD34-HLA-DR- immunophenotype. The lack of CD45 expression is often observed in B-cell acute lymphoblastic leukemia, whereas CD45-negative AML is extremely rare; only one older male with AML-M0 has been reported. In the present case, the CD45-negative blasts had an MPO-CD13＋CD33＋ phenotype, which is similar to AML-M0.

Coexpression of NUP98/TOP1 and TOP1/NUP98 in de novo Acute Myeloid Leukemia with t(11;20)(p15;q12) and t(2;5)(q33;q31).

The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]. Expression of the NUP98/TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2;5) was centromeric to EGR1. In all 10 cases described in the literature, the NUP98 exon 13/TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11;20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML.

Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation.

A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III-IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.

Excessive MET signaling causes acquired resistance and addiction to MET inhibitors in the MKN45 gastric cancer cell line.

The clinical efficacy of MET tyrosine kinase inhibitors (MET-TKIs) is hindered by the emergence of acquired resistance, presenting an obstacle to drug discovery. To clarify the mechanisms underlying acquired resistance to MET-TKIs, we established resistance models by continuous exposure of the MET-amplified gastric cancer cell line MKN45 to MET-TKIs, PHA665752 (MKN45-PR) and GSK1363089 (MKN45-GR). Baseline expression and phosphorylation of MET were elevated in MKN45-PR and MKN45-GR compared to MKN45 cells, and higher concentrations of MET-TKIs were required to inhibit MET phosphorylation compared to parental cells. Alterations in MET previously associated with resistance to MET-TKIs were observed in resistant cells, including elevated MET copy number, observed in both resistant lines compared to MKN45 cells, and the Y1230H mutation, detected in MKN45-PR cells. Notably, the growth of resistant lines was lower in the absence of MET-TKIs, suggesting "addiction" to inhibitors. While MKN45-PR cells exhibited a higher S-phase fraction in the absence of PHA665752, bromodeoxyuridine (BrdU) uptake was identical. Baseline phosphorylation of ATR, Chk1 and p53 and p21(waf1/Cip1) expression was higher in MKN45-PR compared to MKN45 cells, and levels were reduced to those observed in untreated MKN45 cells following PHA665752 treatment. Furthermore, targeted knockdown of MET enhanced the growth of MKN45-PR cells. These findings suggest that alterations in MET leading to acquired MET-TKI resistance, may cause excessive MET signaling, subsequent replication stress and DNA damage response, and intra-S-phase arrest in the absence of MET-TKIs. Thus, partial MET inhibition is necessary for resistant cells to proliferate, a phenomenon we refer to as MET-TKI "addiction".

Myelosuppression grading of chemotherapies for hematologic malignancies to facilitate communication between medical and dental staff: lessons from two cases experienced odontogenic septicemia.

BACKGROUND: Odontogenic diseases can be a risk factor for life-threatening infection in patients with hematologic malignancies during chemotherapy that induces myelosuppression of variable severity. Previous studies noted the necessity of the elimination of all odontogenic foci before hematopoietic stem cell transplantation. To enable planning for the adequate dental intervention, the oral medicine team must understand the general status of patient and the intensity of the chemotherapy, which is sometimes difficult to be fully appreciated by dental staff. Therefore, a simplified grading would facilitate the sharing of information between hematologists, dentists and oral hygienists. This study aimed to introduce our myelosuppression grading of chemotherapies for hematologic malignancies and analyze the timing of occurrence of severe odontogenic infection. METHODS: 37 patients having received various chemotherapies for hematologic malignancies were enrolled. The chemotherapy regimens were classified into four grades based on the persistency of myelosuppression induced by chemotherapy. Mild myelosuppressive chemotherapies were classified as grade A, moderate ones as grade B, severe ones as grade C, and chemotherapies that caused severe myelosuppression and persistent immunodeficiency (known as conditioning regimens for transplant) as grade D. The timing of occurrence of severe odontogenic infection was retrospectively investigated. RESULTS: Two patients (5.4%) had severe odontogenic infections after grade B or C chemotherapy. One occurred after extraction of non-salvageable teeth; the other resulted from advanced periodontitis in a tooth that could not be extracted because of thrombocytopenia. Both were de novo hematologic malignancy patients. During grade D chemotherapy, no patients had severe odontogenic infections. CONCLUSIONS: The simplified grading introduced in this study is considered a useful tool for understanding the myelosuppressive state caused by chemotherapy and facilitating communication between medical and dental staff. During the period around the primary chemotherapy, especially for de novo hematologic malignancy patients who often received grade B to C myelosuppression chemotherapy, caution should be exercised for severe odontogenic infection by the oral medicine team, irrespective of whether invasive treatment is to be performed.

Is CT or FDG-PET more useful for evaluation of the treatment response in metastatic HER2-positive breast cancer? a case report and literature review.

Response evaluation criteria in solid tumors version 1.1 (RECIST ver1.1) has been widely adopted to evaluate treatment efficacy in solid tumors, including breast cancer (BC), in clinical trials and clinical practice. RECIST is based mainly on computed tomography (CT) images, and the role of fluorodeoxyglucose-positron emission tomography (FDG-PET) is limited. However, because the rate of tumor shrinkage on CT does not necessarily reflect the potential remaining tumor cells, there may be a discrepancy between the treatment response and prognosis in some cases. Here we report a case of metastatic human epidermal growth factor receptor 2 (HER2)-positive BC where FDG-PET was preferable to CT for evaluation of the treatment response. A 40-year-old woman became aware of a lump in her right breast in September 201X. She was pregnant and underwent further examinations, including a biopsy, in November. The diagnosis was HER2-positive BC (cT2N2bM1, stage IV). Trastuzumab plus pertuzumab plus docetaxel (TPD) therapy was initiated in December 201X. CT performed in February 201X+1 showed cystic changes in the metastatic lesions in the liver, and the treatment response was stable disease (SD) according to RECIST. However, FDG-PET in March 201X+1 did not detect abnormal uptake of FDG in the hepatic lesions. The disease remained stable thereafter. Thus, tumor shrinkage may not be apparent in situations where the response to treatment results in rapid changes in blood flow within the tumor, which is associated with cystic changes. When patients with hypervascular liver metastases receive treatment with highly effective regimens, the target lesion may show cystic changes rather than shrinkage, as observed in the present case. Therefore, FDG-PET is sometimes superior to CT in judging a tumor response.

Slowly Progressive Bone Marrow Metastasis of Gastric Cancer Followed-up Without Treatment.

BACKGROUND/AIM: Bone marrow metastasis (BMM) of gastric cancer (GC) is complicated by disseminated intravascular coagulation syndrome (DIC), which is more prominent in poorly differentiated carcinoma. This is one of the first case reports of a slowly progressing BMM of GC after approximately 1 year of follow-up without treatment. CASE REPORT: A 72-year-old woman underwent total gastrectomy and splenectomy for GC in February 2012. The pathological diagnosis was that of a moderately differentiated adenocarcinoma. Five years later in December 2017, she developed anemia; however, its cause remained unknown. Due to worsening of the anemia, the patient visited the Kakogawa Central City Hospital in October 2018. Bone marrow biopsy revealed an infiltration of caudal type homeobox 2-positive cancer cells, and our diagnosis was BMM of GC. There was no DIC. The incidence of BMM is high in well- or moderately differentiated breast cancer but rarely causes DIC. CONCLUSION: As with breast cancer, in moderately differentiated cancer cells, BMM of GC may progress slowly after the appearance of symptoms without causing DIC.

Late-onset doxorubicin-induced congestive heart failure in an elderly cancer survivor: A case report.

Background: Recently, the survival rate of patients with cancer has improved annually due to advancements in cancer diagnosis and treatment technologies. Meanwhile, late-onset complications associated with cancer treatment significantly affect survival and quality of life. However, different from pediatric cancer survivors, there is no unified view on the follow-up of late complications in elderly cancer survivors. We reported a case of congestive heart failure as a late-onset complication of doxorubicin (DXR) in an elderly cancer survivor. Case report: The patient is an 80-year-old woman with hypertension and chronic renal failure. She received six cycles of chemotherapy for Hodgkin's lymphoma that started in January 201X-2. The total dose of DXR was 300 mg/m2, and a transthoracic echocardiogram (TTE) performed in October 201X-2, showed good left ventricular wall motion (LVWM). In April 201X, she suddenly developed dyspnea. Upon arrival at the hospital, a physical examination revealed orthopnea, tachycardia, and leg edema. A chest radiograph showed cardiac enlargement and pleural effusion. A TTE showed diffusely reduced LVWM and a left ventricular ejection fraction in the 20% range. After close examination, the patient was diagnosed with congestive heart failure due to late-onset DXR-induced cardiomyopathy. Conclusion: Late-onset DXR-induced cardiotoxicity is considered high-risk from 250 mg/m2 or higher. Elderly cancer survivors are at higher risk of cardiotoxicity than non-elderly cancer survivors and may require closer follow-up.

Delayed diagnosis of bladder cancer in a patient with autosomal dominant polycystic kidney disease.

ABSTRACT: Approximately 50% of autosomal dominant polycystic kidney disease (ADPKD) patients have gross hematuria, but few cases of bladder cancer complications are known. We report a case of a 49-year-old female ADPKD patient with bladder cancer, who was presented to our hospital 4 months after the onset of gross hematuria. A computed tomography (CT) scan showed a bladder mass, enlarged pelvic and left inguinal lymph nodes, multiple liver cysts, and a polycystic kidney. Based on family history, CT scan results, and lymph node biopsy, we diagnosed the patient with uroplakin III-negative bladder cancer with squamous metaplasia and ADPKD. The patient was treated with systemic chemotherapy but died 2 months after the definitive diagnosis. The delayed diagnosis was disastrous, and malignancy should be considered in the differential diagnosis when symptoms suggestive of malignancy such as hematuria appear. Particularly, uroplakin III-negative advanced bladder cancer has a poor prognosis and requires early diagnosis and treatment.

Efficacy and Safety of Synbiotics in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Randomized, Double-blinded, Placebo-controlled Pilot Study.

Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.

Validity of the Cancer and Aging Research Group Predictive Tool in Older Japanese Patients.

Background: This study aimed to evaluate the usefulness of the Cancer and Aging Research Group (CARG) predictive tool in older Japanese patients with cancer. Methods: Patients aged 65 years or older with solid tumors treated with new anticancer regimens in Kakogawa Central City Hospital between April 2016 and March 2019 were included. Grade 3 or higher risks of developing chemotherapy-related adverse events (CRAEs) were calculated using the tool (low-, intermediate-, or high-risk scores). The association between grade 3−5 CRAE incidence during the first course of each regimen and the calculated risk or the patient characteristics was evaluated. The difference in the incidences of CRAEs between the groups was evaluated by Fisher's exact test. Results: This study examined 76 patients (mean age: 71 (65−82) years). The incidence of grade 3−5 CRAE was 38%, 55%, and 76% in patients classified as low, medium, and high CARG risk scores (p = 0.035), and the incidence of severe non-hematological toxicities was 4%, 31%, and 52% (p < 0.01), respectively. Eastern Cooperative Oncology Group performance status and age were not associated with chemotherapy toxicity. Conclusions: The CARG predictive tool was valid, suggesting its usefulness in optimizing chemotherapy outcomes in older patients with cancer.

Difficulty in Distinguishing Pulmonary Arterial Intimal Sarcoma from Pulmonary Thromboembolism Using FDG PET/CT.

BACKGROUND/AIM: Pulmonary arterial intimal sarcoma (PAIS) is a rare malignant soft tissue tumor that is difficult to differentiate from pulmonary thromboembolism (PTE). Therefore, pre-operative diagnosis is often difficult. However, recent advances in fluorodeoxyglucose positron emission tomography (FDG-PET) have enabled the use of standardized uptake values (SUVs) for the differential diagnosis of PAIS from PTE, and the frequency of diagnosis of PAIS has increased. Here, we report a case of PAIS that was difficult to differentiate from PTE despite using FDG-PET. CASE REPORT: A 40-year-old woman presented with gradually worsening exertional dyspnea. Contrast-enhanced computed tomography (CT) revealed lesions with poor enhancement in the right lateral basal pulmonary artery. FDG-PET/CT did not reveal any tumor or thrombosis in other areas. Cytological evaluation using a right ventricular catheter did not lead to a definitive diagnosis. Because the patient did not respond to anticoagulation, we performed pulmonary artery endarterectomy. Pathological examination of the pulmonary artery tumor revealed a mucinous tumor with an edematous stroma and spindle-shaped tumor-cell proliferation, which confirmed the diagnosis of PAIS. However, FDG/PET demonstrated a low SUV of 3.4. CONCLUSION: Some PAISs with low cellular densities and high mucous tissue proportions have SUVs similar to those in PTE. In patients with low FDG uptake, if PAIS is suspected based on other objective findings, additional exploration using highly invasive tests or surgical procedures specific to PAIS is warranted.

Predicting Chemotherapy-Related Adverse Events in Elderly Cancer Patients with Prior Anticancer Therapy.

To test the usefulness of the Cancer and Aging Research Group (CARG) predictive tool, it was used to assess elderly cancer patients with prior anticancer therapy. Among patients with solid malignancies aged ≥ 65 years receiving second-line chemotherapy who were admitted to the Department of Medical Oncology/Hematology at Kakogawa Central City Hospital between April 2016 and September 2019, the risk ≥ grade 3 of developing chemotherapy-related adverse events (CRAEs) (low, intermediate, or high) was calculated using the tool. Correlations between grades 3 and 5 CRAE incidence rates in the first course of each regimen and CARG risk score, age, and Eastern Cooperative Oncology Group performance status (ECOG PS) were assessed. Included patients (n = 62) had a mean age of 71 years (range, 65−82 years). Severe CRAE incidence in patients with low, medium, or high CARG risk was 27%, 54%, and 71%, respectively (p = 0.026). The incidence of severe non-hematological toxicities was 5%, 35%, and 64%, respectively (p < 0.01). There was no association between age or ECOG PS and chemotherapy toxicity. The results suggest the validity of the CARG predictive tool in elderly cancer patients with prior anticancer therapy. Particularly, the tool showed potential for predicting non-hematological toxicity.

Case report: Paratesticular dedifferentiated liposarcoma with poor prognosis.

Background/Aim: Most paratesticular liposarcomas (PLPSs) are well-differentiated liposarcomas (WDLPSs) with favourable prognoses. As such, the rare occurrence of PLPS often leads to its misdiagnosis as a hernia or hydrocele on physical examination. Curative resection of the tumour may not be possible in cases where PLPSs have transformed into dedifferentiated liposarcomas (DDLPSs) owing to a delay in diagnosis. Herein, we describe a case of unresectable paratesticular dedifferentiated liposarcoma (PDDLPS) with poor prognosis due to delayed diagnosis. Case Report: A 57-year-old man visited our hospital with a chief complaint of a right scrotal mass, which was diagnosed as scrotal hydrocele but without treatment or follow-up. Eight years later, the patient complained of abdominal distension, and a computed tomography scan revealed the presence of retroperitoneal and right scrotal masses. The right scrotal mass was removed, and histopathology revealed DDLPS. The patient was diagnosed with unresectable PDDLPS metastasising to the retroperitoneum, and the left pleura was treated with doxorubicin. After an initial response, pleural effusion and ascites increased during the sixth cycle of chemotherapy. The patient subsequently received eribulin but died 5 months after the initial DDLPS diagnosis. Conclusion: It is difficult to distinguish PLPS from benign inguinal hernia and hydrocele testis on physical examination. PLPS generally has a considerably good prognosis. However, failure to diagnose WDLPS can be dangerous as it might lead to malignant transformation to DDLPS, which has a poor prognosis. Physicians should consider this malignancy when examining patients with hernias or hydroceles of the inguinal region and should perform ultrasonography or magnetic resonance imaging.

Detection of a novel CBFB-MYH11 fusion transcript in acute myeloid leukemia M1 with inv(16)(p13q22).

Acute myeloid leukemia (AML) with an inv(16)(p13q22) or t(16;16)(p13;q22) chromosomal abnormality represents one of the most common subtypes of de novo cases. These chromosomal rearrangements result in multiple CBFB-MYH11 fusion transcripts, with type-A being the most frequent. We here describe a unique case of de novo AML-M1, with inv(16)(p13q22), leading to an unusual CBFB-MYH11 fusion transcript, and der(7)t(7;11)(q31;q21). The fusion transcript involves a CBFB exon 5 with a breakpoint at nucleotide 754, an insertion of a 13-bp sequence of CBFB intron 5 at the fusion point, and the MYH11 exon 27 with a breakpoint at nucleotide 3464. To our knowledge, this CBFB-MYH11 fusion transcript has never been reported previously. The clinical characteristics of the present case are in line with previous reports suggesting that rare CBFB-MYH11 fusion transcripts lead to aberrant characteristics such as an atypical cytomorphology and additional cytogenetic abnormalities.

Double-hit pancreatic B-lymphoblastic lymphoma with a variant translocation t(2;18)(p11;q21).

Double-hit lymphoma is typically categorized as "high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements", but in infrequent cases in which terminal deoxynucleotidyl transferase (TdT) expression is positive, it is categorized as B-lymphoblastic lymphoma (B-LBL). BCL2 rearrangements are usually caused by t(14;18)(q32;q21); variant translocations are very rare. Here, we describe an unusual case of double-hit pancreatic B-LBL with a variant translocation t(2;18)(p11;q21). A 69-year-old man was admitted because of an abdominal mass. Computed tomography scans demonstrated a diffusely enlarged pancreas and massive ascites. Cell block preparations of ascites cells revealed marked proliferation of blastic lymphoid cells positive for CD19, CD10, CD79a, PAX5, and TdT, indicating a diagnosis of B-LBL. G-banding and spectral karyotyping showed 45,XY,+X,t(2;18)(p11;q21),-4,der(5)t(1;5)(q12;p15),der(6)t(6;21)(q21;q?),t(8;14)(q24;q32),-15. Fluorescence in situ hybridization detected split BCL2 and IGH/MYC fusion signals. Almost all ascites cells were diffusely and strongly positive for MYC and BCL2. The patient died of progressive disease 20 days after admission. To our knowledge, this is the first reported case of MYC and BCL2 double-hit B-LBL with t(2;18)(p11;q21). High coexpression of MYC by t(8;14) and BCL2 by t(2;18) may be implicated in the development of B-LBL. Furthermore, double-hit B-LBL may be associated with a less favorable outcome compared with typical B-LBL.

Successful Bridging Chemotherapy with Gemcitabine, Carboplatin, and Dexamethasone before Unrelated Stem Cell Transplantation for Hepatosplenic T-cell Lymphoma.

A 45-year-old woman was diagnosed with hepatosplenic T-cell lymphoma (HSTCL), a rare subtype of peripheral T-cell lymphoma. She received different types of chemotherapy, but disease progression was observed. To reduce the tumor burden before an unrelated bone marrow transplantation, combination chemotherapy consisting of the gemcitabine, carboplatin, and dexamethasone (GCD) was administered as bridging therapy, resulting in a reduction in the number of lymphoma cells. We were then able to perform bone marrow transplantation. Although she experienced some adverse events, she successfully achieved long-term remission. We herein report a successful case of HSTCL treated with unrelated stem cell transplantation following the GCD regimen as bridging chemotherapy.

Early lymphocyte recovery predicts clinical outcome after HSCT with mycophenolate mofetil prophylaxis in the Japanese population.

Immune reconstitution affects clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT), and it has been suggested that lymphocyte recovery affects survival after HSCT. However, few studies have examined lymphocyte recovery in Asian patients who received mycophenolate mofetil (MMF) prophylaxis for graft-versus-host disease. We retrospectively evaluated early lymphocyte recovery after HSCT among Japanese adults who received MMF prophylaxis. Patients were divided into two groups according to their median absolute lymphocyte count (ALC) on day 28 after HSCT as follows: the "low ALC group" (≤ 0.22 × 109 cells/L) and the "high ALC group" (> 0.22 × 109 cells/L). With a median follow-up of 317 days, the high ALC group showed significantly better overall survival than the low ALC group (at 1 year: 62 vs. 46%, P = 0.02). The high ALC group also tended to have better non-relapse mortality than the low ALC group (at 1 year: 13 vs. 23%, P = 0.08). There was no significant difference in relapse rate between the high and low ALC groups (at 1 year: 29 vs. 35%, P = 0.2). We conclude that among Japanese patients who received MMF prophylaxis, ALC on day 28 after HSCT was effective in predicting overall survival and non-relapse mortality.