ALBERT

Description: Background: Autologous stem cell transplantation (ASCT) combined with novel therapeutic drugs, including proteasome inhibitors (PIs)/immunomodulatory agents (IMiDs), can substantially improve the prognosis of patients with multiple myeloma (MM). Because MM patients survive longer, the incidence of secondary primary malignancies (SPMs) in long-term survivors is increasing. To date, only few studies have evaluated SPMs in real-world patients, particularly in those with MM in Asia. Aims: To analyze the risk factors of SPMs in MM patients after ASCT before and after the introduction of PIs/IMiDs. Methods: In this retrospective observational study, data from the Registry of the Japan Society for Hematopoietic Cell Transplantation were collected and analyzed. A total of 2340 newly diagnosed MM patients who underwent ASCT between 1993 and 2016 were enrolled in this study. Median age 58 at ASCT (range 22-72); males 1329 (56.8%), females 1011 (43.2%); IgG 1340 (57.3%), IgA 452 (19.3%), IgD 63 (2.7%), IgE 3 (0.1%), IgM 6 (0.3%), BJP 416 (17.8%), non-secreting 38 (1.6%), unknown 22 (0.9%); ISS1 774 (33.1%), ISS2 825 (35.3%), ISS3 455 (19.4%), not assessed 286 (12.2%). 1908 (81.5%) and 432 (18.5%) patients received single melphalan 200 mg/sqm (Mel200) and double Mel200, respectively as conditioning regimen before ASCT. Moreover, 771 (32.9%) and 1569 (67.1%) patients underwent ASCT from 1993 to 2006 and from 2007 to 2016, respectively. 659 (28.2%) patients received PIs, 73 (3.1%) IMiDs and 903 (38.6%) both PIs and IMiDs. Meanwhile, 38 (1.6%) patients received radiation treatment. The disease status at ASCT was as follows: 690 (29.5%), sCR/CR; 580 (24.8%), VGPR; 831 (35.5%), PR; 144 (6.2%), SD; 50 (2.1%), PD; and 45 (1.9%), unknown. Results: The median follow-up from ASCT was 24 (range: 0-218) months. A total of 38 patients in this cohort developed SPMs, with a cumulative incidence of 0.8% [95% confidence interval (CI): 0.4%-1.2%] and 2.4% (95% CI: 1.6%-3.5%) at 24 and 60 months, respectively. Twenty-four solid (4, stomach; 3, breast; 5, lung; 2, liver; 2, pancreas; 2, colon; 1, uterus; 1, thyroid gland; 1, bladder; 2, sarcoma; and 1, basal cell carcinoma), 11 hematologic (7, myelodysplastic syndrome; 1, acute leukemia; 2, lymphoma; and 1, unknown), and 3 unknown tumors were observed. The cumulative incidence of hematologic and solid SPMs at 60 months was 0.8% and 1.7%, respectively. OS at 60 months after ASCT was 62.9%, and OS after the diagnosis of SPMs at 24 months was 70.7% for hematologic and 64.6% for solid SPMs (median follow-up of 23 months). Next, the risk factors affecting the incidence of SPMs were analyzed, which included age at ASCT (≤65 or 〉65 years), sex, PI/IMiD treatment, use of radiation, single/double ASCT, and period of ASCT (1993-2006 or 2007-2016). Because bortezomib, thalidomide, and lenalidomide were released for relapse/refractory MM treatment in Japan in December 2006, February 2009, and July 2010, respectively, we categorized the patients into two treatment cohorts: pre-novel agent era (1993-2006) and novel agent era (2007-2016). Univariate analysis showed that the novel agent era (1.7% vs 4.3% at 60 months; P = 0.013; Fig. 1) and use of radiation (2.3% vs 9.5% at 60 months; P = 0.027) were significant independent risk factors for SPMs. Multivariate analysis revealed that the use of radiation [hazard ratio (HR): 3.895; 95% CI: 1.163-13.050; P = 0.027] was a significant, independent risk factor for SPMs. The novel agent era (HR: 1.716; 95% CI: 0.857-3.438; P = 0.13) and IMiD without PI treatment (HR: 2.206; 95% CI: 0.787-6.189; P = 0.13) were likely high-risk factors for SPMs. In contrast, PI without IMiD treatment (P = 0.79) was not a risk factor for SPMs. The probabilities of developing SPMs and death due to other causes (mainly MM) at 60 months were 2.4% and 36.5% (Fig. 1), respectively, indicating that the risk for SPMs was lower than that for death from MM. Furthermore, OS between the pre-novel and novel agent era groups significantly improved (59.2% vs. 69.5%, P 〈 0.0001) at 60 months after ASCT. Conclusions: The incidence of SPMs in patients with MM in Japan was consistent with that reported recently (Sahebi et al. BBMT, 2018). Although the risk for SPMs increased in the novel agent era group, the mortality rate of SPMs was lower than that of other causes (primarily MM). Considering the increase in the number of long-term survivors with MM, the early occurrence of SPMs should be cautiously monitored. Disclosures Takamatsu: Bristol-Myers Squibb: Honoraria, Research Funding; Ono pharmaceutical: Honoraria, Research Funding; CSL Behring: Research Funding; SRL: Consultancy, Research Funding; Daiichi-Sankyo Company: Honoraria; Becton, Dickinson and Company: Honoraria; Sanofi: Consultancy, Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Fujimoto Pharmaceutical: Honoraria; Janssen Pharmaceutical: Consultancy, Honoraria; Abbvie: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Mizuno:Takeda Pharmaceutical Co., Ltd.: Honoraria; Bristol-Myers Squibb Corporation: Honoraria; Celgene Corporation: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria. Fuchida:Japan Blood Products Organization: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Daiichi-Sankyo Company: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Ono pharmaceutical: Honoraria; Kyowa Kirin: Honoraria; SEKISUI MEDICAL CO., LTD.: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria. Hanamura:Asai Clinic: Research Funding; Yamada Yohojo: Research Funding; AbbVie: Honoraria; Chugai: Research Funding; Eli Lilly: Research Funding; Taiho: Research Funding; Sanofi: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; Pfizer: Honoraria, Research Funding; Eisai: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Fukuyu Hospital: Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Nihon Shinyaku: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Shionogi: Honoraria, Research Funding; Fujimoto: Research Funding; MSD: Research Funding; Zenyaku: Research Funding; Ono: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Mundi: Honoraria. Nakamura:Astellas Pharma Inc.: Honoraria; Takeda Pharmaceutical Company Limited: Research Funding; Eisai Co. Ltd.: Honoraria; Kyowa Kirin: Research Funding. Mori:Celgene: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Bristol-Myers Squibb: Honoraria; Ono Pharmaceutical: Honoraria; Novartis Pharma K.K: Honoraria. Tsukada:Chugai Pharmaceutical Co.,Ltd: Honoraria; Kyowa Kirin: Honoraria; Celgene: Honoraria; Ono Pharmaceutical: Honoraria; Sanofi: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria; MOCHIDA PHARMACEUTICAL CO., LTD.: Honoraria; Asahi Kasei Pharma Corporation: Honoraria; Ohtsuka Pharmaceutical: Honoraria; Fujimoto Pharmaceutical: Honoraria. Ichinohe:Astellas Pharma: Research Funding; Chugai Pharmaceutical Co.: Research Funding; CSL Behring: Research Funding; Eisai Co.: Research Funding; Kyowa Hakko Kirin Co.: Research Funding; Ono Pharmaceutical Co.: Research Funding; Pfizer: Research Funding; Nippon Shinyaku Co.: Research Funding; MSD: Research Funding; Otsuka Pharmaceutical Co.: Research Funding; Repertoire Genesis Inc.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; Taiho Pharmaceutical Co.: Research Funding; Takeda Pharmaceutical Co.: Research Funding; Zenyaku Kogyo Co.: Research Funding; Alexion Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; JCR Pharmaceuticals: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria. Kanda:Pfizer: Research Funding; Novartis: Research Funding; Mochida: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Nippon-Shinyaku: Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Shionogi: Consultancy, Honoraria, Research Funding; Ono: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Nippon-Shinyaku: Research Funding; Ono: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; CSL Behring: Research Funding; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Asahi-Kasei: Research Funding; Tanabe Mitsubishi: Research Funding; Novartis: Research Funding; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Shionogi: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria; Takara-bio: Consultancy, Honoraria; Tanabe Mitsubishi: Research Funding; Asahi-Kasei: Research Funding; MSD: Research Funding; Alexion: Consultancy, Honoraria; Takara-bio: Consultancy, Honoraria; Celgene: Consultancy, Research Funding; Mochida: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Research Funding; CSL Behring: Research Funding; MSD: Research Funding; Otsuka: Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Dainippon Sumitomo: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding; Sanofi: Research Funding; Dainippon Sumitomo: Consultancy, Honoraria, Research Funding; Taisho-Toyama: Research Funding; Sanofi: Research Funding; Taiho: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Taisho-Toyama: Research Funding; Celgene: Consultancy, Research Funding; Taiho: Research Funding. Atsuta:CHUGAI PHARMACEUTICAL CO., LTD.: Honoraria; Kyowa Kirin Co., Ltd: Honoraria. Sunami:Takeda: Honoraria, Research Funding; GSK: Research Funding; Sanofi: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Research Funding; Ono: Honoraria, Research Funding; Alexion-pharma: Research Funding; Daiichi Sankyo: Research Funding; MSD: Research Funding; Abbvie: Research Funding; Celgene: Honoraria, Research Funding; Janssen: Research Funding.

Description: Abstract 2281 Poster Board II-258 Background: A decision analysis using the Markov process is a flexible and convenient analytical method that tracks the clinical events that occur after a certain decision with different probabilities and utilities over time. To address the role of allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) in CR1, we performed a Markov decision analysis using newly collected clinical data from 2029 patients. Methods: Probabilities and other outcome data were derived from a database of adult AML patients that was constructed from case report files collected for this study. We included patients who were diagnosed with AML other than M3 between 1999 and 2006, aged 16 to 70 years, and who had achieved CR1 after 1 or 2 courses of induction chemotherapy. Using the software package TreeAge Pro 2009, we constructed a Markov decision model that compared 2 strategies: allo-HCT in CR1 (HCT group) and no allo-HCT in CR1 (CTx group). Possible health states considered in each decision included, for the HCT group, 1) no relapse without chronic GVHD, 2) no relapse with chronic GVHD, 3) relapse, and 4) dead, and, for the CTx group, 1) no relapse, 2) relapse, 3) second remission, 4) after salvage allo-HCT, and 5) dead. Quality-of-life (QOL) adjustments were made by incorporating time trade-off utilities that were derived from a questionnaire to 12 physicians who were familiar with the treatment of AML. The cycle length between state transitions was set at 3 months. Results: A total of 2029 patients were eligible for this analysis. The median age was 50 years, and the median follow-up of the surviving patients was 4.10 years. The proportions of patients with favorable, intermediate, unfavorable and unknown cytogenetic risk by SWOG criteria were 20%, 54%, 17% and 9%, respectively. Therapies performed at CR1 were allo-HCT in 494 patients (24%) and chemotherapy in 1535 patients (76%). Among 1076 patients whose HLA typing was performed for allo-HCT in CR1, 431 had HLA-matched or 1-antigen-mismatched related donors. Life expectancy and quality-adjusted life expectancy for the HCT and CTx groups in each risk category are summarized in Table 1. Life expectancy of the HCT group was longer than that of the CTx group (4.96 years vs. 4.44 years). However, quality-adjusted life expectancy of the HCT group was comparable to that of the CTx group (4.06 years vs. 3.98 years) due to a larger reduction of expected life length in the HCT group after QOL adjustment. In a subset analysis of the CTx group, patients with more favorable cytogenetic risk had a longer life expectancy. Whereas allo-HCT in CR1 was associated with a shorter life expectancy in patients with favorable-risk AML, allo-HCT in CR1 was associated with a longer life expectancy in those with intermediate-risk or unfavorable-risk AML. Adjustment for QOL did not change the preferred decision in the intermediate- and unfavorable-risk groups, although the survival advantages for allo-HCT in CR1 were less than those without QOL adjustment. In a subset of patients who had related donors, both life expectancy and quality-adjusted life expectancy were longer in the HCT group. Conclusion: The results of our decision analysis using the Markov process indicated that patients with intermediate- or unfavorable-risk AML have a longer life expectancy and quality-adjusted life expectancy with a decision of allo-HCT in CR1. Our results also showed that a Markov decision analysis that incorporates QOL may be useful as a decision-making tool for patients who might be candidates for allo-HCT. Disclosures: No relevant conflicts of interest to declare.

Description: Objectives Fever during neutropenia occurs in 〉 90% and 80% of allogeneic and autologous hematopoietic stem cell transplantation (HSCT) recipients, respectively. Current guidelines recommend the prophylaxis with fluoroquinolones (FQs) in HSCT patients. Although there is evidence that antibiotic prophylaxis improve clinical outcome in patients with chemotherapy-induced neutropenia, prophylactic antibiotic therapy has not been thoroughly evaluated in HSCT recipients. Therefore, we performed a meta-analysis to evaluate the impact of systemic antibiotic prophylaxis in HSCT recipients on mortality, incidence of infection and related adverse events. Data sources We identified reports that were not restricted to those in English and not restricted to published trials through PubMed, the Cochrane Library, and references of identified studies. Review Methods We included prospective, randomized studies on systemic antibiotic prophylaxis in HSCT recipients. The outcome measures included the all-cause mortality, infection-related mortality, febrile episodes, incidence of clinically or microbiologically documented infection, bacteremia, or related adverse events. The summarized odds ratios (ORs) were calculated using the Mantel–Haenszel method and the DerSimonian–Laird method. Results Seventeen trials with 1453 patients (842 autologous and 407 allogeneic HSCT recipients) were included. The percentage of autologous and allogeneic HSCT recipients was not specified in 2 trials. Systemic antibiotic prophylaxis was compared with placebo or no prophylaxis in 10 trials and with non-absorbable antibiotic in 2 trials, respectively. Systemic antibiotics other than FQs were evaluated in five out of these 12 trials. Four trials evaluated the effect of addition of antibiotics for gram positive bacteria to FQs. Remaining 1 trial compared the two different systemic antibiotic regimens, FQs versus trimethoprim sulfamethoxazole. As a result, systemic antibiotic prophylaxis reduced the incidence of febrile episodes (OR 0.16; 95 percent confidence interval [CI], 0.09-0.30), clinically or microbiologically documented infection (OR 0.41; 95% CI 0.30-0.57) and bacteremia (OR 0.37; 95% CI 0.26-0.53) without the significant effect on all-cause mortality or infection-related mortality (OR 0.89; 95% CI 0.48-1.66, OR 1.37; 95% CI 0.50-3.76, respectively). Impact of prophylaxis with FQs on mortality was inconclusive because of small number of clinical trials evaluated. Adverse events increased in patients with systemic antibiotic prophylaxis compared to controls (OR 3.32; 95% CI 1.45-7.63). In meta-regression, percentage of allogeneic HSCT recipients was not associated with each outcome measure. With regard to the comparison between different prophylactic regimens, addition of antibiotics for gram positive bacteria to FQs decreased the incidence of bacteremia (OR 0.44; 0.24-0.80) without significant effects on all-cause mortality, infection related death and febrile episodes. There was not significant, but consistent decrease in clinically or microbiologically documented infection (OR 0.55; 95% CI 0.30-1.01). There was significant increase of adverse events in patients receiving addition of antibiotics for gram positive bacteria to FQs (OR 6.65; 95% CI 2.15-20.54). Conclusions Systemic antibiotic prophylaxis successfully reduced the incidence of infection in HSCT recipients. However, there was no significant impact on mortality. Impact of prophylaxis with FQs on mortality in HSCT recipients was inconclusive because of small number of trials evaluated. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3084 With modern intensive chemotherapy, 78% to 93% of adult patients with acute lymphoblastic leukemia (ALL) achieve complete remission (CR). However, the disease-free survival rate is only 30% to 40% due to the high rate of relapse. A part of relapsed patients can achieve second remission (CR2) with salvage therapy, and allogeneic hematopoietic stem cell transplantation (HSCT) in CR2 will be the only curative strategy. Prognosis after relapse in adult patients with ALL is considered to be extremely poor, but reports as to the outcome after relapse have been limited. To elucidate the outcome of relapsed patients and prognostic factors after relapse, we retrospectively collected and analyzed clinical data from 69 institutions in Japan on patients with Philadelphia-chromosome (Ph) negative ALL, aged 16–65 years, who relapsed after first CR (CR1) between 1998 and 2008. A total of 332 patients were included in this study. The median age of them was 35 years, and 165 patients were male. Median duration of CR1 was 290 days (range 15–7162 days), and median follow-up time after relapse was 319 days (range 3–3689 days). Fifty-eight and 4 of them relapsed after allogeneic and autologous HSCT in CR1, respectively. The overall survival (OS) rate was not significantly different between patients who relapsed after allogeneic HSCT in CR1 and those who relapsed after chemotherapy only (50.0% vs. 43.4% at 1 year and 10.6% vs. 16.3% at 5 year, respectively). Among 270 patients who relapsed after chemotherapy only, 234 patients received salvage chemotherapy after relapse, and 123 patients achieved CR2 (52.5%). Sixty-two patients out of those 123 patients underwent allogeneic HSCT in CR2. Median duration between the achievement of CR2 with salvage chemotherapy and allogeneic HSCT in CR2 was 76 days. OS rate was significantly better in patients who underwent allogeneic HSCT in CR2 following salvage chemotherapy than those who did not (74.1% vs. 55.1% at 1 year and 44.7% vs. 11.6% at 5 year, respectively) by a landmark analysis limiting patients who were surviving without disease at 76 days after the achievement of CR2. In multivariate analysis of factors that included allogeneic HSCT in CR2 following salvage chemotherapy as a time-dependent covariate, lower white blood cell count at relapse (less than 10000/μl) and allogeneic HSCT in CR2 were associated with better OS rate among patients who achieved CR2 following salvage chemotherapy. Forty-six patients underwent allogeneic HSCT in non-CR after receiving salvage chemotherapy. A part of them survived long, and 5 year OS rate was 20.9%. In conclusion, the prognosis of adult patients with relapsed Ph-negative ALL is poor. Allogeneic HSCT after first relapse could improve the prognosis. Disclosures: No relevant conflicts of interest to declare.

Description: Varicella-zoster virus (VZV) infection remains a common complication after hematopoietic stem cell transplantation (HSCT). The introduction of long-term prophylaxis with low-dose acyclovir against VZV reactivation has been investigated, because VZV-related complications including post-herpetic neuralgia and secondary infection significantly affect the patient’s quality of life. We started long-term oral acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least one year after transplantation. To evaluate the efficacy of this long-term prophylaxis with ultra low-dose acyclovir against VZV reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic HSCT for the first time from June, 1995 to November, 2006 at University of Tokyo Hospital. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. There was no VZV-related death. Only one breakthrough reactivation occurred during long-term acyclovir, responding well to the therapeutic dose of valacyclovir. The use of long-term acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20.4% vs 50.5%, P

Description: The role of chemotherapy before allo-SCT remains unclear. We analyzed the data of 283 patients (median age 41 years, range 16–65 years) who underwent allo-SCT from an HLA-identical sibling donor for MDS that were reported to the Japan Society for Hematopoietic Cell Transplantation. One hundred eighty-eight patients had received chemotherapy before allo-SCT (Chemo group), whereas 95 had not (NoChemo group). The Chemo group included significantly higher proportion of patients with advanced disease and poor karyotype than the NoChemo group, (p

Description: To clarify which is preferable, a related donor with an HLA-1 Ag mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host (GVH) direction (RD/1AG-MM-GVH) or an HLA 8/8-allele (HLA-A, HLA-B, HLA-C, and HLA-DRB1)–matched unrelated donor (8/8-MUD), we evaluated 779 patients with acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome who received a T cell–replete graft from an RD/1AG-MM-GVH or 8/8-MUD. The use of an RD/1AG-MM-GVH donor was significantly associated with a higher overall mortality rate than the use of an 8/8-MUD in a multivariate analysis (hazard ratio, 1.49; P 〈 .001), and this impact was statistically significant only in patients with standard-risk diseases (P = .001). Among patients with standard-risk diseases who received transplantation from an RD/1AG-MM-GVH donor, the presence of an HLA-B Ag mismatch was significantly associated with a lower overall survival rate than an HLA-DR Ag mismatch because of an increased risk of treatment-related mortality. The HLA-C Ag mismatch or multiple allelic mismatches were frequently observed in the HLA-B Ag-mismatched group, and were possibly associated with the poor outcome. In conclusion, an 8/8-MUD should be prioritized over an RD/1AG-MM-GVH donor during donor selection. In particular, an HLA-B Ag mismatch in the GVH direction has an adverse effect on overall survival and treatment-related mortality in patients with standard-risk diseases.

Description: Cardiac toxicity due to conditioning regimens is a critical problem in the hematopoietic stem cell transplantation (HSCT). High-dose cyclophosphamide, which is a major component of conventional myeloablative regimens, is considered to be a main cause of cardiac toxicity. Although reduced intensity conditioning regimens have been developed in order to diminish regimen related toxicities for patients with pre-transplant co-morbidity, their anti-neoplastic effects have been revealed to be insufficient especially for patients with acute lymphoblastic leukemia. Therefore, it is imperative to establish an alternative preparative regimen with myeloablative intensity for patients with impaired pre-transplant cardiac function. From June 1995 at the University of Tokyo, we have adopted a heart protective regimen (VP/rCY/TBI) which is composed of continuous infusion of VP-16 20 mg/kg for 2 days, CY 40 mg/kg for 1 day, and 12 Gy of fractionated total body irradiation (TBI) for 17 patients because they had impaired cardiac function defined by ejection fraction (EF) less than 0.55 (n=15) or a history of congestive heart failure (n=1) or pulmonary hypertension (n=1). The clinical relevance of VP/rCY/TBI regimen was evaluated by retrospectively comparing the outcome of VP/rCY/TBI recipients with that of conventional CY/TBI (CY 60 mg/kg for 2 days + fractionated TBI 12 Gy, which was administered to 140 patients during the same period) recipients. The characteristics analysis revealed that VP/rCY/TBI recipients had higher cumulative doses of anthracyclines (354 mg/m2 vs 150 mg/m2 calculated as the equivalence of native doxorubicin, p

Description: Late occurrence of viral infections beyond day 100 after hematopoietic stem cell transplantation (HSCT) was widely recognized to depend on the profound immune suppression due to severe chronic GVHD and its treatment. However, there have been few reports clarifying the direct relationships between the development of late viral infections and immune reconstitution after HSCT. To evaluate the correlation of the immune recovery with the occurrence of late cytomegalovirus (CMV) or varicella-zoster virus (VZV) infections, we retrospectively analyzed the records of 60 Japanese adult patients who underwent allogeneic HSCT for the first time from April, 2002 to February, 2007 at the University of Tokyo Hospital, and survived longer than 180 days after HSCT. Absolute lymphocyte subset counts (CD3+ T cells, CD3−CD19+ B cells, CD3+CD4+ helper T cells, CD4+CD45RO+ memory T cells, CD4+CD45RA+ naïve T cells, CD3+CD8+ cytotoxic T cells, CD3−CD56+ natural killer cells), absolute monocyte counts, serum IgG, IgA, and IgM levels were measured at 3 and 6 months after HSCT. As a prophylaxis against late CMV disease, risk-adopted preemptive therapy with ganciclovir was performed by monitoring CMV antigenemia beyond day 100 after HSCT. For late VZV disease, oral administration of acyclovir at 200 mg/day was principally continued until the end of immunosuppressive therapy and at least one year after HSCT in 52 patients, whereas valacyclovir at 500 mg/day three times a week was administered until one year after HSCT in eight patients. Two out of 60 patients have already developed CMV disease within 100 days after HSCT. Thirteen of the remaining 58 patients developed late CMV infection defined as 10 or more CMV-Ag positive cells per two slides at a median of 125 days (101 to 546 days) after HSCT. CD3+ T cells less than 400x106/L (P=0.003), CD3+CD4+ T cells less than 200 x106/L (P=0.013), CD4+CD45RO+ T cells less than 100x106/L (P