Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Next-generation sequencing-based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse.

Next-generation sequencing (NGS) has been applied to define clinically relevant somatic mutations and classify subtypes in acute myeloid leukemia (AML). Persistent allelic burden after chemotherapy is associated with higher relapse incidence, but presence of allelic burden in AML patients after receiving allogeneic hematopoietic cell transplantation (HCT) has not been examined longitudinally. As such, we aimed to assess the feasibility of NGS in monitoring AML patients receiving HCT. Using a targeted gene panel, we performed NGS in 104 AML patients receiving HCT using samples collected at diagnosis, pre-HCT, and post-HCT at day 21 (post-HCTD21). NGS detected 256 mutations in 90 of 104 patients at diagnosis, which showed stepwise clearances after chemotherapy and HCT. In a subset of patients, mutations were still detectable pre-HCT and post-HCT. Most post-HCT mutations originate from mutations initially detected at diagnosis. Post-HCTD21 allelic burdens in relapsed patients were higher than in nonrelapsed patients. Post-HCTD21 mutations in relapsed patients all expanded at relapse. Assessment of variant allele frequency (VAF) revealed that overall VAF post-HCTD21 (VAF0.2%-post-HCTD21) is associated with an increased risk of relapse (56.2% vs 16.0% at 3 years; P < .001) and worse overall survival (OS; 36.5% vs 67.0% at 3 years; P = .006). Multivariate analyses confirmed that VAF0.2%-post-HCTD21 is an adverse prognostic factor for OS (hazard ratio [HR], 3.07; P = .003) and relapse incidence (HR, 4.75; P < .001), independent of the revised European LeukemiaNet risk groups. Overall, current study demonstrates that NGS-based posttransplant monitoring in AML patients is feasible and can distinguish high-risk patients for relapse.

18F-FDG PET/CT is useful for determining survival outcomes of patients with multiple myeloma classified as stage II and III with the Revised International Staging System.

PURPOSE: This study evaluated the prognostic role of 18F-FDG PET/CT at baseline in patients with newly diagnosed multiple myeloa (MM) and evaluated the prognostic relevance of 18F-FDG PET/CT for each stage according to the Revised International Staging System (R-ISS). METHOD: We retrospectively analyzed the records of 167 patients with newly diagnosed MM. 18F-FDG PET/CT was performed prior to induction therapy in patients with newly diagnosed MM. RESULTS: In the total cohort, the presence of more than three hypermetabolic focal lesions (FLs) or extramedullary disease (EMD) on baseline PET/CT was associated with significantly inferior progression-free survival (PFS) and overall survival (OS) than other patients. Because most patients (91%) with EMD had more than three FLs, PET/CT positivity was defined as the presence of more than three FLs or the presence of EMD. In multivariate analyses, PET/CT positivity was an independent predictor of PFS and OS in all patients. Fifty-five patients (46.1%) with R-ISS II were PET/CT-positive at baseline and had significantly shorter PFS and OS. PET/CT positivity was also correlated with poor PFS and OS in patients with R-ISS III. CONCLUSION: 18F-FDG PET/CT was an independent predictor of survival outcomes in patients with newly diagnosed MM. In addition, performing 18F- FDG PET/CT at diagnosis may be useful for determining the survival outcomes of MM patients with R-ISS II and III.

Thalidomide-based induction regimens are as effective as bortezomib-based regimens in elderly patients with multiple myeloma with cereblon expression.

Cereblon (CRBN) has been identified as a primary target of immunomodulatory drugs and is considered a biomarker for the prediction of outcomes after thalidomide- or lenalidomide-based treatments. In this study, we evaluated CRBN expression in bone marrow (BM) tissue at diagnosis and investigated the relationship between CRBN expression and treatment outcomes after thalidomide- or bortezomib-based front-line therapies in 89 elderly patients with multiple myeloma (MM). CRBN expression at the time of diagnosis was evaluated with immunohistochemical (IHC) staining for myeloma cells in paraffin wax-embedded BM tissue. CRBN-immunostained slides were scored by intensity and diffuseness, and a total score of >6 was defined as CRBN-positive (CRBN(+)). Thirty-eight patients (45.2 %) were CRBN(+). Among patients treated with thalidomide-based regimens, CRBN(+) patients showed a better treatment response than did CRBN-negative patients (35.0 vs. 11.8 % complete response rate, respectively; HR = 4.038, P = 0.137). During a median follow-up of 31.8 months, patients treated with bortezomib-based regimens had a longer time to progression (TTP) than did patients treated with thalidomide-based regimens (15.6 vs. 13.2 months, respectively; P = 0.047), but early mortality occurred frequently in patients treated with bortezomib-based regimens. Additionally, there was no significant difference in survival outcomes between thalidomide- and bortezomib-based regimens in CRBN(+) patients (median TTP, 13.8 vs. 15.6 months, respectively; P = 0.842 and median OS, 39.3 vs. 30.1 months, respectively; P = 0.074). These data suggest that thalidomide-based regimens are as effective as bortezomib-based regimens in elderly patients with MM who are CRBN(+). Thus, CRBN positivity, by IHC staining, may be useful in deciding appropriate treatment options in elderly patients with MM.

Normal karyotype acute myeloid leukemia patients with CEBPA double mutation have a favorable prognosis but no survival benefit from allogeneic stem cell transplant.

Normal karyotype acute myeloid leukemia (NK-AML) with CCAAT/enhancer binding protein α (CEBPA) mutations is known to have a more favorable prognosis. However, direct comparison of the clinical significance according to consolidation therapy has not been widely performed in patients with NK-AML. A total of 404 patients with NK-AML who received intensive induction chemotherapy were included in the present study. Diagnostic samples from the patients were evaluated for CEBPA mutations by direct sequencing. CEBPA single (sm) or double mutation (dm) was observed in 27 (6.7 %) and 51 (12.6 %) patients, respectively. CEBPA (dm) was associated with GATA2 (mut), and it was less frequently associated with FLT3-ITD(pos), NPM1 (mut), and DNMT3A (mut) in comparison with CEBPA (wild) or CEBPA (sm) (all p values <0.05). On multivariate analysis, CEBPA (dm) (p = 0.007, OR 39.593) was an independent risk factor for achievement of complete remission (CR). With a median follow-up of 40.1 months, CEBPA (dm) showed a favorable overall survival (OS), event-free survival (EFS), and lower relapse incidence (RI) in comparison with CEBPA (wild) (all p values <0.005). Comparison of clinical outcome analyses (consolidation chemotherapy vs. allogeneic hematopoietic cell transplantation (HCT)) demonstrated the role of consolidation treatment in patients with CEBPA (dm). Allogeneic HCT was associated with lower EFS and RI and a trend of higher non-relapse mortality. However, there was no statistically significant difference in OS. In conclusion, CEBPA (dm) was associated with other molecular mutations. Consolidation chemotherapy alone may overcome higher relapse rates by reducing the treatment mortality and increasing survival after relapse events in patients with CEBPA (dm) in NK-AML.

Pralatrexate in Combination with Bortezomib for Relapsed or Refractory Peripheral T Cell Lymphoma in 5 Elderly Patients.

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.

Decreased body mass index is associated with poor prognosis in patients with multiple myeloma.

Obesity increases morbidity in and mortality of patients with various types of cancer. However, the proportion of obese individuals in Asia is smaller than that in Western populations and only a few studies have explored the effect of obesity at the time of diagnosis on the survival of Asian patients with multiple myeloma (MM). Therefore, we investigated the relationship between body mass index (BMI) at diagnosis, and clinical manifestations, in MM patients. We also measured overall survival (OS) in terms of BMI groupings. Patients were subdivided into three groups based on hazard ratios (HRs) associated with BMIs of <20, 20-24.9, and ≥25 kg/m(2). The median survival times were 25.5 months in patients with a BMI of <20 kg/m(2), 56.8 months for those with a BMI of 20-24.9 kg/m(2), and 76 months in patients with a BMI of ≥25 kg/m(2). Patients with a BMI of <20 kg/m(2) exhibited poorer performance status and a lower hemoglobin level at diagnosis than did others, and renal failure (serum creatinine ≥2 mg/dl) was much more often observed in such patients than in those of other groups. Both univariate and multivariate analyses showed that BMI <20 kg/m(2) (HR 1.831, 95 % confidence interval [CI] 1.005-3.337; P = 0.048) and performance of autologous stem cell transplantation (HR 0.257, 95 % CI 0.139-0.475, P < 0.001) were significantly (negatively) associated with OS. In conclusion, a low BMI (<20 kg/m(2)) at the time of diagnosis was associated with poor survival of MM patients.

Gynecologic problems and healthcare behavior by shift patterns in Korean nursing staff.

We aimed to evaluate the clinical impact of shift patterns at work on gynecologic problems and the healthcare behavior of Korean nursing staff. We conducted a web-based survey for over two weeks in September 2021, involving female nursing staff, including nurses, nurses' aides, and nursing assistants, working in five medical centers. The questionnaire included 40 questions on baseline characteristics, working information, and experiences with gynecologic problems and medical approaches. Overall, 885 nursing staffs participated in the survey, of the 1,904 who received the invitation with an online link of the survey. The response rate was 46.5%. Among the participants responding to all questions, 569 (64.4%) worked two or three shifts and 305 (34.5%) worked full-time. In women rotating two or three-shift patterns, irregular menstrual cycles (21.6% vs. 13.8%, p = 0.005), abnormal menstrual cycles (40.9% vs. 33.8%, p = 0.038), and dysmenorrhea (48.0% vs. 38.4%, p = 0.006) were more frequent than in those who worked full-time. The experience of visiting gynecologic clinics (47.5% vs. 44.1%, p = 0.332) and treating gynecologic conditions (33.4% vs. 29.3%, p = 0.211) did not differ according to the working patterns. However, diagnosis of gynecologic diseases was more frequent in women working full-time (36.4% vs. 29.7%, p = 0.043). The rates of screening (76.1% vs. 57.8%, p<0.001) and human papillomavirus vaccination (55.7% vs. 39.9%, p<0.001) for cervical cancer prevention were higher in women working full-time than in two-three shifts. This study showed that rotating shift work may be related to an increase in gynecologic problems and a decrease in cancer prevention activity among female nursing staff.

Reduced-Intensity Conditioning with Busulfan and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Lymphoblastic Leukemia.

PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation. MATERIALS AND METHODS: Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m²/day of fludarabine for 5 or 6 days were analyzed. RESULTS: The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26-1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II-IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively. CONCLUSION: RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.

Autologous stem cell transplantation in elderly patients with multiple myeloma in Korea: the KMM1807 study.

Autologous stem cell transplantation (ASCT) is not frequently performed for elderly patients multiple myeloma (MM) in Korea, despite its being a standardized approach for young patients. Medical records of 150 patients from 15 Korean institutions who received ASCT at age ≥ 64 years were analyzed retrospectively. Patients included had symptomatic MM, and had received their first ASCT at age ≥ 64 following induction chemotherapy. The main outcome was the response after ASCT. Overall survival (OS) and progression-free survival (PFS) were also analyzed. Median time to ASCT was 6.3 months. Complete response plus stringent complete response rate increased from 36 (24.0%) to 105 (70.0%) after ASCT, and high-quality response (≥ very good partial response) increased from 96 (64.0%) to 125 (83.3%). With a median follow-up of 32.6 months after ASCT, 5-year OS and PFS were 59.7% and 22.8%, respectively. Febrile neutropenia occurred in 43.5%, and nausea (21.3%) and stomatitis (13.2%) were common grade 3-4 non-hematologic adverse events. Of 44 deaths, disease progression (n = 23) was the most common cause of mortality, followed by infection (n = 13). Treatment-related death occurred in four cases (2.7%). ASCT is an effective and safe option for elderly MM patients and is associated with superior clinical outcomes.

Efficacy and Safety of Melphalan, Cyclophosphamide and Dexamethasone (MCD) as a Salvage Treatment for Patients with Relapsed/Refractory Multiple Myeloma.

This study investigated the efficacy and safety of melphalan, cyclophosphamide, and dexamethasone (MCD) as a salvage regimen for heavily treated relapsed or refractory multiple myeloma patients. We retrospectively analyzed a total of 27 patients who received the MCD regimen between April 2011 and November 2013. The MCD regimen consisted of oral melphalan 6.75 mg/m2 on days 1-4, once-weekly dose of oral cyclophosphamide 300 mg/m2 and dexamethasone 20 mg/m2 on days 1-4 and days 15-18. Each cycle was repeated every 28 days. The median age of the patients was 66 years and the MCD regimen was initiated at a median 37.7 months from diagnosis. Patients received a median of five regimens including autologous stem cell transplantation. The overall response rate was 25.9% (very good partial response 3.7%, partial response 22.2%) and 8 (29.6%) patients achieved a minor response. Median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2-8.5) ; overall survival 11.7 months (95% CI, 5.4-16.6). Grade 3 or 4 neutropenia and thrombocytopenia were observed in 51.8% and 33.3%, respectively. Although the overall response rate is relatively low, the MCD regimen may have a role as a bridge to a novel regimen in heavily pretreated patients with MM.

Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype.

This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10.7% (n = 42) with AML with mutated chromatin or RNA-splicing genes or both, 1.5% (n = 6) with AML with TP53 mutations, 13.5% (n = 53) with AML with biallelic CEBPA mutations, 2.0% (n = 8) with AML with IDH2-R172 mutations and no other class-defining lesion, 29.5% (n = 116) with AML with driver mutations but no detected class-defining lesion, 4.3% (n = 17) with AML with no detected driver mutation, and 3.8% (n = 15) patients with AML who met the criteria for ≥2 genomic subgroups. The 5-year overall survival and relapse rate of subgroup in AML with mutated chromatin, RNA-splicing genes, or both was 11.6% (95% CI = 1.4-21.8%) and 71.4% (95% CI = 45.7-86.5%), respectively. This study suggests that the recently recommended genomic classification is an appropriate and replicable categorization system in the NK AML population. The subgroup of AML with mutated chromatin, RNA-splicing genes, or both showed extremely poor survival in NK-AML; thus, a novel approach is needed to improve their prognosis.

STAT3 expression is associated with poor survival in non-elderly adult patients with newly diagnosed multiple myeloma.

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is not only a key signaling molecule in the regulation of growth but is also involved in malignant transformation. We investigated the prognostic significance of STAT3 expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly diagnosed multiple myeloma (MM). METHODS: Tumor cell-specific phosphotyrosine-STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual immunohistochemical (IHC) staining for PY-STAT3 and CD138. RESULTS: PY-STAT3 positivity was detected in 10 patients (10.6%), including three who showed strong expression. PY-STAT3-positive patients had higher serum C-reactive protein and calcium levels at diagnosis than did PY-STAT3-negative patients. PY-STAT3 positivity had predictive value for poor progression-free survival (PFS; P=0.001) and overall survival (OS; P=0.003). Among the 60 patients who received frontline autologous stem cell transplantation, PY-STAT3-positive patients had poorer PFS than did PY-STAT3-negative patients (4.2 vs. 19.2 mo, respectively; P=0.013). Multivariate analysis identified PY-STAT3 expression as an independent prognostic factor for PFS (relative risk [RR]=2.706, P=0.014) and OS (RR=3.091, P=0.044). CONCLUSION: These data show that PY-STAT3 positivity, as determined using dual IHC, is a marker of poor prognosis in non-elderly adult patients with MM.

5-Hydroxymethylcytosine correlates with epigenetic regulatory mutations, but may not have prognostic value in predicting survival in normal karyotype acute myeloid leukemia.

Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC). Both TET2 and IDH1/2 mutations can impair the production of 5hmC, thus decreasing 5hmC levels. TET2 or IDH1/2 mutations are commonly observed in acute myeloid leukemia (AML). However, the implications of 5hmC on survival in normal karyotype AML patients have not been fully evaluated. The 5hmC levels were analyzed in 375 patients using ELISA. The levels of 5hmC in DNA samples were converted to a log scale for the analysis and correlations with TET2 and/or IDH1/2 mutations were evaluated. The median 5hmC level was 0.065% (range 0.001-0.999). Mutation rates were 13.1% for TET2mut, 6.7% for IDH1mut, and 13.9% for IDH2mut. The prevalence of TET2 and/or IDH1/2 was 33.1% (124/375). TET2 and IDH1/2 mutated patients had significantly lower levels of log(5hmC) compared with patients without TET2 or IDH1/2 mutations (p<0.001). With a median follow-up of 55.5 months (range, 0.7-179.8), there was no significant difference in overall survival, event-free survival, and relapse risk according to TET2mut or IDH1/2mut (all, p>0.05). To identify its prognostic value, we sub-classified the levels of 5hmC into tertiles for 5hmC values. However, there was no significant association between the categories of 5hmC levels and survival or relapse risk (all p>0.05). Patients with TET2 or IDH1/2 mutations had lower levels of 5hmC. The 5hmC levels may not be predictive of survival in patients with normal karyotype AML.

Effect of Abdominal Massage before In Vitro Fertilization Injection on Alleviating Pain among Infertile Women.

PURPOSE: The purpose of this study was to evaluate the effect of abdominal massage on alleviating pain caused by the injection of recombinant gonadotropin for In Vitro Fertilization (IVF) among infertile women. METHODS: This study employed a nonequivalent control group non-synchronized design. A total sample of 149 infertile women who never experienced in vitro fertilization was recruited at C fertility center. Seventy women were assigned into experimental group and 79 into controls. The experimental group had been informed to do abdominal massage prior to the injection and to record their subjective pain using visual analogue scale. The control group had been informed to record their subjective pain in the same way just after the injection. RESULTS: Compared to the pre-tested pain scores, the pain scores in experimental group were significantly reduced by 0.7 points, whereas the control group increased by 0.9 points (t=-4.55, p=.001). CONCLUSION: This study confirms that the use of abdominal massage prior to the injection is an effective way to alleviate pain on injection site. This massage may be a useful intervention for infertile women about pain alleviation.

A Comparative Study of Anxiety, Pain and Maternal-fetal Attachment between Women who became Pregnant after Infertility Treatment and became Pregnant Naturally.

PURPOSE: This study was a comparative study to understand the levels of anxiety, pain and maternal-fetal attachment between women who became pregnant after infertility treatment and became pregnant naturally. METHODS: This study used a comparative survey design. Data were collected by 50 couples of natural pregnancy and of who became pregnant after infertility treatment who visited delivery room in C Medical hospital, Seoul. These couples were to have first baby, and cervix dilatation of women was less than 3 cm regardless of diagnosis. RESULTS: The score of anxiety of infertile women was significantly higher than that of naturally pregnant women; however, that of spouses showed no difference. The pain score for infertile women was significantly higher in both the active and transition phases. Pain scores that reported by their spouses did not show differences in either phase. The score of maternal-fetal attachment showed no difference between two groups of women. CONCLUSION: The result showed the importance of nursing intervention to reduce women's anxiety and pain, through both antenatal-childbirth education programs and assertive nursing interventions. It is necessary to develop and evaluate new intervention which would be more effective for reducing pain and anxiety for couples who became pregnant after infertility treatment.

Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic.

Although the introduction of stem cell transplantation and novel agents has improved survival, multiple myeloma (MM) is still difficult to cure. Alternative approaches are clearly needed to prolong the survival of patients with MM. Dendritic cell (DC) therapy is a very promising tool immunologically in MM. We developed a method to generate potent DCs with increased Th1 polarization and migration ability for inducing strong myeloma-specific cytotoxic T lymphocytes. In this review, we discuss how the efficacy of cancer immunotherapy using DCs can be improved in MM.

Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation.

BACKGROUND/AIMS: BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. METHODS: Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. RESULTS: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. CONCLUSIONS: Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.