Objective: The aim of this study was to reveal the efficacy and safety of rabbit antithymocyte globulin (rATG) in patients with aplastic anemia (AA).
Patients: This study included 17 consecutive patients in Tenri Hospital from May 2009 through November 2013 who were diagnosed with AA and first treated with rATG in combination with or without cyclosporine (CS), including one who had been previously treated with CS alone.
Results: Ages ranged from 8 to 81, with a median of 68. The diseases included 5 non-severe (NSAA), 7 severe (SAA), and 5 very severe AA (VSAA). Paroxysmal nocturnal hemoglobinuria (PNH)-type cells were present in 11. Rabbit ATG was administered at a dose of 2.5 or 3.75 mg/kg/day. Cyclosporine was concurrently given to all but one. At 6 months, 10 (71%) of 14 evaluable patients achieved a partial response (PR) and 2 finally fulfilled the criteria for a complete response. Nine (75%) of the 12 NSAA/SAA patients achieved a PR or more, while the hematological response in 3 of 4 VSAA patients at >6 months did not reach the level of PR. The percentage of PNH-type cells showed no significant change after treatment. Three patients aged >75 years old died, including 2 with unexpected cardiopulmonary arrest. With a median follow-up of 504 days, the overall survival rate at 2 years was 79%.
Conclusion: This study indicates that rATG is the treatment of choice for NSAA/SAA patients who are ineligible for allogeneic transplantation. However, we should be cautious when using rATG for aged patients.

View full abstract

Background: Transient tachypnea of the newborn (TTN) is one of the most common respiratory disorders in newborns. Risk factors for TTN include cesarean section, male sex, and premature delivery. Here, we examined the risk factors of TTN in our hospital in order to find a tool for early diagnosis.
Methods: We performed a retrospective review of 444 babies who were born in our hospital between April 2012 and March 2013. TTN was diagnosed in 34 babies (TTN group). Eighty-seven babies had tachypnea or grunting, but improved upon routine care within 12 hours (non-TTN group). Two hundred and sixty-five babies had no symptoms or problems (control group). Fifty-eight babies suffered from infectious diseases, among others (other disease group). We compared the sex, gestational age, birth weight, vaginal delivery or cesarean section, and Apgar score among the TTN group, the non-TTN group, and the control group.
Results: The percentage of the TTN group was 7.7% among all newborn babies, making it the most common disease of newborn babies in our hospital. In the comparison among these 3 groups, there were no significant differences in sex or maternal age, but the average gestational days were 269.6 in the TTN group, 274.3 in the non-TTN group, and 274.1 in the control group, which was significantly lower in the TTN group than in the other 2 groups. The average birth weights were 2,795.7 g in the TTN group, 2,951.5 g in the non-TTN group, and 2,989.8 g in the control group; the birth weight was significantly lower in the TTN group than in the control group. The proportions of cesarean section were 24% in the TTN group, 14% in the non-TTN group, and 10% in the control group; this rate was significantly higher in the TTN group than in the control group. The proportions of premature rupture of membrane were 21% in the TTN group, 31% in the non-TTN group, and 14% in the control group; this rate was significantly higher in the non-TTN group than in the control group. There was no significant difference in fetal distress among these 3 groups. The median Apgar scores at 1 min were 8 in the TTN group, and 9 in the non-TTN group and the control group, which were significantly different; the score was the lowest in the TTN group, intermediate in the non-TTN group, and the highest in the control group. The median Apgar scores at 5 min were 9 in the TTN group and 10 in the non-TTN and control groups; it was the lowest in the TTN group.
 When the conditions of gestational week ≤38 weeks (gestational day ≤272), Apgar score at 1 min ≤8, and Apgar score at 5 min ≤9 were combined, the prevalence of TTN was 59% (10 out of 17 babies); otherwise, it was 7% (24 out of 369 babies), which was significantly different.
Conclusion: Gestational age, birth weight, cesarean section, and Apgar score were related to TTN in our study. When gestational week ≤38 weeks, Apgar score at 1 min ≤8, and Apgar score at 5 min ≤ 9 were combined, the prevalence of TTN was more than 50%.

View full abstract

 A 66-year-old woman presented with stage III diffuse large B-cell lymphoma. She was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy; however, profound cytopenia requiring long-term transfusion subsequently appeared, and acute monocytic leukemia finally developed 10.5 months after the first dose of R-CHOP. G-banding and fluorescence in situ hybridization (FISH) using the MLL break-apart probe determined that the leukemia cells carried t(11;17)(q23;p13).ish t(11;17)(q23;p13)(5'MLL+,3'MLL-;3'MLL+), and reverse-transcriptase polymerase chain reaction and nucleotide sequencing determined that MLL exon 9 fused to GAS7 (growth arrest specific 7) exon 2 in frame. Reevaluation of bone marrow cells by MLL-FISH showed that leukemia cells with the MLL rearrangement had appeared as early as 6.5 months after starting R-CHOP. It remains to be determined whether the MLL-GAS7 rearrangement had occurred before the exposure to chemotherapy or whether this case represented therapy-related leukemia induced by the topoisomerase II inhibitor, doxorubicin. The presence of MLL-GAS7-positive cells in prodromal hematopoietic hypoplasia suggested that these cells exerted a suppressive effect on normal hematopoiesis.

View full abstract

 A 78-year-old woman was admitted to our hospital with tarry stools. Endoscopic examination of the small intestine by oral single-balloon enteroscopy revealed irregular ulcerated lesions with bleeding at the proximal ileum. The patient underwent exploratory laparotomy with resection of a segment of the small intestine as well as the regional mesenteric lymph nodes. Histopathological examination of the surgical specimen revealed transmural infiltrates of centrocyte-like lymphoma cells with a marginal zone distribution. The lymphoma cells had a CD5^-, CD10^-, CD19⁺, CD20⁺, CD21⁺, CD22^+weak, and CD23^- immunophenotype, and expressed α/λ-type immunoglobulins. The karyotype was 46,XX,t(11;18)(q21;q21)/47,idem,+der(11)t(11;18)(q21;q21), and fluorescence in situ hybridization on the interphase nuclei confirmed the BIRC3-MALT1 fusion. The presence of IgA-λ-type monoclonal proteins in the serum and BIRC3-MALT1-positive cells with plasma cell morphology in the bone marrow indicated that the lymphoma was a disseminated disease. The patient was treated with 6 doses of rituximab; however, her serum IgA levels remained high. The centrocyte-like cytomorphology of lymphoma cells with marginal zone distribution and the presence of t(11;18)(q21;q21)/BIRC3-MALT1 fulfilled the diagnostic criteria of extranodal marginal zone lymphoma of the MALT type. The incidence of this type of lymphoma developing in the small intestine may increase with the introduction of balloon-assisted enteroscopy.

View full abstract

 With the progress of cancer therapy, there have been increasing demands for validation of the measures of its therapeutic efficacy and benefit. We briefly review such measures, including 5-year survival rate, cure rate, median and mean survival times, log-rank statistics and hazard ratio, as well as the endpoints advocated by the US Food and Drug Administration (FDA). These are evaluated from the perspective of patients. The results show that 1) although the 5-year survival rate is easily appreciable to patients and non-statisticians, it tends to overestimate the cure rate; 2) generally, cured patients have longer survival times and better QOL than those whose deaths are merely delayed, so the cure rate should be the measure of primary importance, rather than the time to event, particularly if the group under study has a potentially curable fraction; and 3) if the time to death from cancer is delayed, the QOL may be reduced against the patient's wishes. In conclusion, measures of efficacy and benefit in cancer therapy have yet to be improved by giving more consideration to cure rate and patient preference.

View full abstract

 Primary central nervous system lymphoma (PCNSL) is an uncommon subtype of non-Hodgkin lymphoma, the lesions of which are confined to the CNS without evidence of systemic disease. The vast majority of PCNSL show the diffuse large B-cell lymphoma histopathology. Patients with PCNSL present with focal neurological deficits, neuropsychiatric symptoms, signs of raised intracranial pressure, and seizures. Periventricular lesions are most common, and the lesions appear isointense to hypointense on T1-weighted MRI images and isointense to hyperintense with respect to cortex on T2-weighted MRI images, and show marked enhancement after contrast medium administration. PCNSL is primarily treated with high-dose methotrexate (HD-MTX)-containing chemotherapy, followed by whole-brain radiation therapy (WBRT) of 40 to 45 Gy, leading to complete response rates of 30% to 87% and 5-year overall survival rates of 22% to 70%. However, delayed neurocognitive decline accounting for the combined effects of HD-MTX and WBRT can occur, especially in elderly patients. We encountered a total of 10 patients with PCNSL during the last 3 years. The treatment included HD-MTX-containing intensive chemotherapy, intraventricular administration of cytotoxic drugs through Ommaya reservoir in place, high-dose chemotherapy with autologous hematopoietic stem cell support, and WBRT; however, only one patient showed disease-free survival of over 2 years. On the other hand, systemic malignant lymphoma can involve the nervous system at any level. The most common site of CNS relapse is the meninges, and patients typically present with cranial nerve deficits. For patients with CNS relapse, systemic HD-MTX is suggested as for those with PCNSL; however, survival has been poor, with a median of 2 to 5 months. Thus, administration of CNS prophylaxis should be incorporated into the initial treatment of patients at high risk of CNS relapse.

View full abstract