Validation of pretransplantation assessment of mortality risk score in the outcome of hematopoietic SCT in non-Caucasians.

The Pretransplantation Assessment of Mortality (PAM) score is a risk score for mortality after allogeneic hematopoietic SCT (HSCT). Ethnicity is a genetically determined factor that correlated with immune-mediated outcomes of allogeneic HSCT. We evaluated the predictive value of the PAM score for transplant outcome in 276 Japanese populations in which transplant-related complications occur less frequently than Caucasians. The PAM score effectively risk-stratified these patients for survival; overall survival (OS) at 2 years was 100%, 80.2%, 49.4%, and 13.9% in the categories 1, 2, 3, and 4, respectively, showing a clear distinction of OS by categories (P<0.001). In addition, the PAM score is useful for the prediction of transplant outcomes both in patients with standard-risk underlying diseases and those with high-risk diseases. The PAM score developed in Caucasian populations is thus useful in non-Caucasian populations.

Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group.

Peripheral T-cell lymphoma (PTCL) is generally characterized by poor prognosis after conventional chemotherapy compared with aggressive B-cell lymphoma. To elucidate the role of high-dose chemotherapy (HDCT) with auto-SCT, we retrospectively analyzed the outcomes of 39 patients with PTCL who received HDCT and auto-SCT between 1990 and 2005. Eleven patients were histologically typed as angioimmunoblastic, nine as anaplastic large-cell lymphoma, seven as natural killer/T-cell lymphoma and twelve as PTCL unspecified. Clinical conditions at transplantation were complete response (CR) in 27 patients and non-CR in 12 patients. Thirty-two patients received a pre-transplant conditioning regimen (MCEC) comprising ranimustine, carboplatin, etoposide and CY, and seven did other TBI-based regimens. Rapid engraftment was obtained in all cases, and transplant-related death was not seen. An estimated 5-year OS was 62.1% with a median follow-up of 78 months. The 5-year OS was significantly higher in patients transplanted during complete response than in those during other disease status (71.4% vs 27.3%, P=0.046). HDCT supported by auto-SCT may therefore be effective as consolidation in CR for PTCL treatment.

Infectious complications in patients receiving autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

Long-term analysis of infectious complication after high-dose immunosuppressive therapy with CD34-selected autologous hematopoietic stem cell transplantation for patients with severe autoimmune diseases (AD) was performed. Theoretically, CD34 selection can reduce the risk of reinfusion of autoreactive lymphocytes. However, it is also associated with a significant reduction in T cells, natural killer cells, and monocytes, which in turn may compromise immune reconstitution, thereby increasing the risk of infection. Moreover, AD compromises host immunity and causes organ damage resulting in dysfunction of the cutaneous or mucosal barrier. In this study, the incidence rate of infections is reported in 14 patients who underwent high-dose (200 mg/kg) cyclophosphamide therapy followed by reinfusion of CD34-selected autologous peripheral blood stem cells. Bacterial complication occurred in 3 of 14 (21%) patients. Cytomegalovirus reactivation and adenovirus hemorrhagic cystitis were observed in 9 (64%) and 2 (14%) patients, respectively. As for late infectious complications, 7 patients (50%) developed dermatomal varicella zoster virus infection. No infection-related mortality was seen in this case series. Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic workup, and prophylactic strategies similar to those applicable to allogeneic recipients are warranted.

Disseminated tuberculosis following second unrelated cord blood transplantation for acute myelogenous leukemia.

Here we report the case of a 43-year-old Japanese woman with acute myelogenous leukemia who underwent 2 unrelated cord blood transplantations (UCBT), terminating in fatal disseminated tuberculosis (TB). The patient did not achieve remission despite intensive chemotherapy, and subsequently underwent UCBT with a standard conditioning regimen. However, engraftment was not achieved. Fifty days after the first UCBT, the patient underwent a second UCBT with a reduced-intensity conditioning regimen. She developed a pre-engraftment immune reaction, which responded well to prednisolone, and engraftment was documented. However, 50 days after the second UCBT, the patient presented with high fever and developed pneumonia despite antibiotic and antifungal treatments. Thereafter, Mycobacterium tuberculosis was detected in blood cultures and specimens of bronchoalveolar lavage, thus indicating disseminated TB. Despite anti-tuberculous treatment, she died on day 85. TB should always be considered as a possible diagnosis when treating febrile immunocompromised patients.

Rituximab does not compromise the mobilization and engraftment of autologous peripheral blood stem cells in diffuse-large B-cell lymphoma.

To investigate effects of the preautografting administration of rituximab on the mobilization and engraftment of peripheral blood stem cells (PBSC), we retrospectively analyzed the outcomes of 43 newly diagnosed diffuse-large B-cell lymphoma patients who received CHOP chemotherapy with or without rituximab as a first-line treatment before autologous PBSC transplantation (PBSCT). There was no difference in the number of CD34(+) cells among PBSC between the non-rituximab and the rituximab groups. Although B-cells were completely depleted from PBSC in the rituximab group, we found no difference in the expression of CXCR-4, VLA-4 and c-Kit on PBSC, indicating that rituximab did not affect the expression of these adhesion molecules, which might be involved in the mechanism of mobilization. There was no significant difference in the recovery of neutrophils and platelets, transplant-related toxicity and post-transplant complications between the two groups. Despite the short follow-up, there was no significant difference in progression-free survival between the two groups. These results indicated no adverse effect of rituximab on the mobilization and engraftment of PBSC. Larger studies are required to determine the impact of rituximab on the mobilization and function of PBSC as well as whether a survival advantage exists in patients who undergo auto-PBSCT with rituximab.

Evans' syndrome following autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

A 34-year-old woman with non-Hodgkin's lymphoma received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). She developed Evans' syndrome, the association of immune thrombocytopenia and autoimmune hemolytic anemia, 49 days after transplantation. Multiple autoimmune disorders may occur concurrently after autologous PBSCT.

Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation: comparison of an antigenemia assay and quantitative real-time polymerase chain reaction.

Cytomegalovirus (CMV) antigenemia and quantitative real-time polymerase chain reaction (PCR) were compared for monitoring of CMV reactivation after allogeneic stem cell transplantation. The number of CMV antigen-positive cells by the antigenemia assay and the level of CMV DNA by real-time PCR correlated well. The sensitivity and specificity of the antigenemia assay was 55.4% and 95.5%, respectively, using real-time PCR as the reference standard. The probability of positive antigenemia at day 100 was 76.5%, with a median of first detection at day 37 in 51 patients, compared with a positive PCR of 84.3% and day 33, respectively. When HLA-identical sibling donor transplant recipients and other donor transplant recipients were analyzed separately, there was no difference between the two tests. However, temporal patterns of first detection of CMV antigen-positive cells and CMV DNA differed between HLA-identical and alternative recipients; patients without CMV (29%) or with sporadic positive PCR results (14%) were more common in HLA-identical sibling transplants, whereas patients with simultaneous antigenemia and positive PCR occurred more in alternative transplants (48%). Two of 51 patients (4%) developed CMV colitis despite antigenemia-guided prophylaxis, but both were successfully treated with ganciclovir. Although PCR is more sensitive than antigenemia, both tests are useful in the early detection of CMV after allogeneic stem cell transplantation.

[Clinical trials of cefroxadine on skin and soft tissue infections in the field of pediatrics (author's transl)].

CXD was administered orally at an average dose of 28.6 mg/kg (18.3 approximately 42.3 mg/kg) for an average 6 days (3 approximately 12 days) to a total of 99 pediatric cases with skin and soft tissue infections (impetigo 89, abscess 7 and furuncle 3) ranging from 3 months to 9 years old. The drug was given twice to 4 times per day after meals. The clinical and bacteriological effects and adverse reactions of CXD as well as the susceptibility of the causative organisms against CXD and CEX were studied, and the results obtained are as described below: 1. According to judgement of the attending doctors, CXD had a high global efficacy rate of 90.9%. 2. Analysis of the attending physicians' evaluations of the clinical effects on impetigo revealed that a dose of CXD 20.5 approximately 30.4 mg/kg t.i.d. can produce satisfactory responses. 3. According to the assessments by Evaluation Committee, the global clinical effects after 3, 5 and 7 days were 81.4, 91.2 and 94.6%, respectively. This indicates that clinical responses increased with prolongation of the treatment period, viz. better responses obtained after 5 and 7 days. This suggests that a minimum of 5 days administration is required for treating these infections. 4. As for impetigo having the largest number of patients in this study, a dose of CXD 20.5 approximately 30.4 mg/kg per day seemed to produce satisfactory clinical effects. 5. As for dose per day, the t.i.d. regimen of CXD 20.5 approximately 30.4 mg/kg seemed to exhibit satisfactory clinical responses, as already mentioned. Because of quite a small number of patients on the q.i.d. regimen of higher doses, however, the question of whether the t.i.d. treatment with 20.5 approximately 30.4 mg is adequate or not should be determined by a comparative study between the q.i.d. and t.i.d. treatments. 6. As for bacteriological responses, a high global effect of 87.1% was obtained with CXD against S. aureus and S. pyogenes isolated from 74 and 1 cases, respectively. 7. As for impetigo with predominant number of cases, CXD was highly effective bacteriologically at a daily dose of 20.5 approximately 30.4 mg/kg t.i.d. As an appropriate comparative evidence with the q.i.d. treatment was lacking, however, therapeutic validity of the t.i.d. treatment could not be determined definitely. 8. Utility was evaluated by the attending physicians on the total 99 cases, and CXD showed as high as 88.9%. 9. There were neither non-compliances nor adverse reactions to this treatment. 10. CXD showed a distribution of antimicrobial activity similar to that of CEX, against 74 isolates of S. aureus with the MICs of CXD ranging from 1.56 to 25 mcg/ml and those of CEX ranging from 0.78 to 25 mcg/ml, with peak MIC being 3.13 mcg/ml for both drugs. As for S. pyogenes, only one isolate from the same species, CXD was antimicrobial activity at 0.2 mcg/ml and CEX was antimicrobial at 0.39 mcg/ml. The above findings suggest that CXD is highly effective against acute skin and soft tissue infections in pediatrics.

[Absorption, excretion and clinical trials of cefroxadine in the field of pediatrics (author's transl)].

A study was made with the newly developed cefroxadine (CXD) dry syrup by measuring the serum level, urine excretion and recovery rate in 10 children who were orally administered 5, 10 and 20 mg/kg at 1 hour after meals and the following results were gained. Also, its clinical efficacies and side effects were investigated in the following cases who were treated with a mean dose of 33 mg/day divided into 3 to 4 portions for a period of 9 days on the average; viz. a total of 151 cases consisting of 9 cases of pharyngitis, 39 of tonsillitis, 11 of streptococcal infection, i.e. scarlet fever, 7 of bronchitis, 6 of pneumonia, 1 of otitis media, 6 of purulent lymphadenitis, 1 of purulent parotitis, 1 of subcutaneous abscess and 3 of impetigo. 1. The serum level tends to reach its maximum level within 1 hour after administration. The mean concentrations of 5, 10 and 20 mg/kg dose in the foregoing time were 6.35, 9.12 and 21.62 mcg/ml respectively and dose response was observed. CXD showed higher concentration than CEX, CED and CFT. The mean half-life periods of the 3 dose were 72, 84 and 66 minutes respectively and variations were observed, but the drugs maintains a satisfactory serum level. 2. The time which showed highest urine excretion was mainly in the 0 to 2 hours bracket and the average concentrations of 5 , 10 and 20 mg/kg dose in the foregoing time were 381.2, 771.7 and 1,577.7 mcg/ml respectively. The dose response was more evident than in the serum concentrations. The average recovery rates within 6 hours were 93.6, 88.3 and 94.3% respectively and they were similar to those of CEX, CED and CFT. 3. The clinical effects were evaluated were in 148 cases out of the total of 151 and 136 cases, or 91.9% showed good or excellent efficacy response. 4. The daily dose groups of less than 30 mg/kg and 31 to 40 mg/kg formed the majority and there was no difference in the comparison of the clinical effectiveness in these 2 groups. Administration of a daily dose of 20 to 40 mg/kg is sufficient for the treatment of the aforementioned mild diseases except for pneumonia. 5. The clinical effects were compared between the 3 and 4 times a day treatment groups, but there was no difference between these two groups with regard to the foregoing daily dose. The 3 times a day treatment is acceptable, but the 4 times a day treatment is preferable when pharmacokinetics if taken into account. 6. The bacteriological effects in 41 cases, or 97.6% out of the 42 cases were above the efficacy base line and a high efficacy rate was achieved. 7. With regard to side effects, diarrhea developed in 4 cases and eosinophilia in 6 cases, abnormal simultaneous increases in GOT and GPT in 1 case and 1 case each for abnormal values in LDH and BUN were seen in the clinical test values. The foregoing results show that CXD has high efficacy and safety and it can be said that it is a drug required in the pediatric field.