Patients Received Granulocyte Colony-stimulating Factor Research Articles

The Effect of High Intensity Interval Exercise on Platelet Engraftment in Autologous Bone Marrow Transplantation (BMT).

Background: Thrombocytopenia is a frequent complication after hematopoietic stem cell transplantation (HSCT). Although platelet transfusion is the most used treatment for severe thrombocytopenia, it is associated with well-established risks. High-intensity interval exercise (HIIE) results in thrombocytosis. Therefore, this study aimed to reduce thrombocytopenia by increasing platelet count through exercise. Materials and Methods: Twenty lymphoma and multiple myeloma patients were divided into HIIE and control groups. To determine the maximal exercise capacity, patients in the HIIE group performed a graded exercise test. All patients received granulocyte colony-stimulating factor for 5 days,followed by a HIIE trial. After 5 min warm up at 10 to 20% of peak power, patients in the HIIE group performed an HIIE protocol that included 12 intervals of one-minute work at 100% peak power interspersed by one-minute active rest at 20% of peak power. Patients in the control group were seated for the same duration without any physical activity. Two blood samples were taken before and immediately after the trials and were analyzed for measuring complete blood count. Results: Platelet count on the day of platelet engraftment in the HIIE group was significantly higher than in the control group (P=0.02). Single-donor platelet transfusion was significantly lower in the HIIE group than in the control group (P=0.05). Conclusion: Based on the findings of the present study, a short bout of HIIE had a positive effect on platelet engraftment through thrombocytosis and reduced platelet transfusion and its complications, which could be a useful strategy for HSCT patients.

Oxaliplatin- versus cisplatin-based regimens for elderly individuals with advanced gastric cancer: a retrospective cohort study

BackgroundWhether an oxaliplatin- or cisplatin-based regimen is more optimal for treating elderly patients with advanced gastric cancer, in terms of survival and adverse events remains unclear.MethodsIn this retrospective cohort study, we used stacked claim data of residents in two Japanese prefectures collected between 2012 and 2017 and between 2014 and 2019, respectively. We included patients with advanced gastric cancer who received oxaliplatin-based and cisplatin-based regimens. Propensity score overlap weighting analysis was conducted to compare overall survival and granulocyte colony-stimulating factor use during chemotherapy between the oxaliplatin- and cisplatin-based treatment groups.ResultsA total of 242 patients were included in the study. After propensity score weighting, Kaplan–Meier analysis showed no significant differences in overall survival between the two groups (hazard ratio: 1.13; 95% confidence interval, 0.60–2.11; p = 0.70). However, the proportion of patients receiving granulocyte colony-stimulating factor was significantly lower in the oxaliplatin group than in the cisplatin group (2.3% vs.22.7%, p = 0.01).ConclusionsSurvival did not differ significantly between elderly patients with advanced gastric cancer treated with oxaliplatin-based versus cisplatin-based regimens; however, the oxaliplatin-based regimen was associated with less granulocyte colony-stimulating factor use.

Association Between Granulocyte Colony-Stimulating Factor (G-CSF) Use and Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) Among Elderly Patients with Breast, Lung, or Prostate Cancer.

Patients diagnosed with cancer have an increased risk both for myelodysplastic syndromes (MDS) and for acute myeloid leukemia (AML) following treatment. Using SEER-Medicare data, we selected patients aged 66years and older who completed systemic therapy between 2002 and 2014 for breast (stageI-III), lung (stageI-III), or prostate (stageI-IV) cancer. For each cancer, we estimated the risk of a composite endpoint of MDS or AML in patients receiving granulocyte colony-stimulating factor (G-CSF) vs. not. The 10-year cumulative risk difference (granulocyte colony-stimulating factor [G-CSF] - no G-CSF) for MDS-AML was 0.45% (95%CI 0.13-0.77%) in breast cancer and 0.39% (95%CI 0.15-0.62%) in lung cancer. G-CSF use was associated with a hazard ratio of 1.60 (95%CI 1.07-2.40) in breast cancer and 1.50 (95%CI 0.99-2.29) in lung cancer. Filgrastim use was associated with a hazard ratio of 1.01 (95%CI 1.00-1.03) per administration in breast cancer and 1.02 (95%CI 0.99-1.05) per administration in lung cancer. Pegfilgrastim was associated with a hazard ratio of 1.08 (95%CI 1.01-1.15) per administration in breast cancer and 1.12 (95%CI 1.00-1.25) per administration in lung cancer. Analyses in prostate cancer were limited because of the low number of events. The use of G-CSF in patients diagnosed with breast and lung cancer is associated with an increased risk of MDS-AML. However, the MDS-AML absolute risk difference is very low.

Post-Transplantation Cyclophosphamide and Short-Term Methotrexate for Tolerance Induction in HLA-Haploidentical Transplantation for Severe Aplastic Anemia

Background. Haploidentical related donors (HIDs) are attractive donors for patients with severe aplastic anemia (SAA) because they are readily available for nearly all the patients. Bone marrow transplant (BMT) using post-transplant cyclophosphamide (PTCy) has been shown effective to cross the immune barriers between the recipients and their HIDs. Short-term low dose of methotrexate (ST-MTX) has long been adopted either alone or combined with calcineurin inhibitors to get across the immune barrier in hematopoietic stem cell transplant (HSCT).Aim of the study. We presented the outcome of 15 patients with SAA who underwent haploidentical transplant (HIT) using T-cell-replete peripheral graft and combination of PTCy with ST-MTX.Patients and grafts. We analyzed the medical records of 15 patients with SAA between Jan 2015 and July 2017. The transplants were either upfront (8/15) or rescue treatment (7/15). The median age of the patients was 16 (range 5-39) years and 66.7% (10/15) were male. All the patients received granulocyte colony-stimulating factor (G-CSF) mobilized peripheral graft from haploidentical related donors. The median mononuclear cells (MNCs) was 12.4 × 108 cells/kg recipient ideal body weight (IBW) with the range of (7.0-22.0) × 108 cells/kg, the CD34+ cell was 7.5 × 106 cells/kg with the range of (5-23) × 106 cells/kg and the CD3+ cells was 2.7 × 108 cells/kg with the range of (1.8-5.0) × 108 cells/kg.Conditioning regimen and GvHD prophylaxis. We used a TBI-free transplantation platform named FBC+PTCy/ST-MTX. Fludarabine was administered at 40 mg/m2 IV daily for 5 days. Busulfan was delivered in a total dose of 6.4mg/kg. Cyclophosphamide was given 14.5 mg/kg daily for 2 days. PTCy was administered at 60mg/kg/day IV on days +3 and +4 post-transplant. Low doses of MTX were delivered on days +1, +2 and +5 post-transplant at 15mg/m2, 10mg/m2 and 10mg/m2. Cyclosporine was given from day +6 through day +180 with the target through level 150~180ng/ml and then was tapered until 12 months post transplant. Mycophenolate mofetil (MMF) was given from day +6 to +35 days for the first 3 patients and then was eliminated for the following patients.Results.Neither primary nor secondary graft failure (GF) was seen in this study. Neutrophil engrafted at 15 days (range, 13-18 days). Platelets engrafted at 19 days (range, 14-36 days) and recovered over 100 × 109/L at 38 days (range, 14-77 days). The time to total lymphocytes recovery over 0.5 × 109/L for 3 consecutive days was 34 days (range, 25-72 days). The accumulated engraftment of neutrophil and platelets were both 100% at +40 days. (Figure 1-A, B.)The cumulative incidence of aGvHD at 100 days was 20.0%(3/15). Two patients had grade I skin aGvHD and the other one had grade II skin aGvHD. No grade III-IV aGvHD was seen. 12 patients were evaluable for the incidence of cGvHD and none of them developed moderate or sever cGvHD with a median of 150 (102-806) days post transplant. (Figure 1-C, D.) During the follow-up, one patients had skin cGvHD and received systemic therapy with corticoid. The treatment was discontinued after 8 months post transplant. All 3 patients, who survived beyond 12 months post transplant at the end of our follow-up, were off immunosuppress.With a median follow-up of 230 days (range 41-806 days), all the patients are alive. They are transfusion independent with karnofsky performance status scale (KPS) scores 100.Conclusion.This study shows that haploidentical related transplant can be successfully applied using T-cell-repleted peripheral grafts. ST-MTX may facilitate PTCy to achieve a stable engraftment with a minimal risk of GvHD in HIT for patients with SAA. Our approach should expand the donor pool for patients with SAA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

YF-H-2015005, a CXCR4 Antagonist, for the Mobilization of Hematopoietic Stem Cells in Non-Hodgkin Lymphoma Patients: A Randomized, Controlled, Phase 3 Clinical Trial

Background: YF-H-2015005, a novel CXCR4 antagonist, has been proven to increase the quantities of circulating hematopoietic stem cells (HSCs), which results in an adequate collection of HSCs in non-Hodgkin lymphoma (NHL) patients.Methods: This was a multicenter, double-blind, randomized (1:1), placebo-controlled phase III clinical trial. All patients received granulocyte colony-stimulating factor (G-CSF) for up to 8 consecutive days. YF-H-2015005 or placebo was administrated on the evening of day 4 and continued daily for up to 4 days. Apheresis was conducted 9–10 h after each dose of YF-H-2015005 or placebo. The primary endpoint was the proportion of NHL patients procuring ≥5 × 106/kg CD34+ HSCs within ≤4 apheresis sessions.Results: In total, 101 patients with NHL were enrolled. The proportions of patients achieving primary endpoint were 57 and 12% in YF-H-2015005 and placebo groups, respectively (P < 0.001). Moreover, a higher proportion of YF-H-2015005-treated patients reached a minimum target collection of ≥2 × 106/kg CD34+ HSCs in ≤4 apheresis days compared to placebo-treated patients (86 vs. 38%, P < 0.001). Furthermore, the median time to collect ≥2 or 5 × 106/kg CD34+ HSCs were 1 and 3 days in YF-H-2015005-treated patients, but 4 days and not reached in placebo-treated patients, respectively. No severe treatment emergent adverse events were observed in both YF-H-2015005 treatment and placebo groups.Conclusions: YF-H-2015005 plus G-CSF regimen was a tolerable combination with high efficacy, which might be used to rapidly mobilize and collect HSCs in NHL patients.

Elderly Aggressive-Histology Non-Hodgkin's Lymphoma: First-Line VNCOP-B Regimen Experience on 350 Patients

Age is a risk factor and a prognostic parameter in elderly aggressive-histology non-Hodgkin's lymphoma (NHL) patients. Several adapted chemotherapeutic regimens have recently been designed and tested on elderly patients. Several of these trials have shown that older aggressive-histology NHL patients can benefit from specific and adequate treatment capable of curing a percentage of these patients. Between January 1992 and September 1997, 350 previously untreated aggressive-histology NHL patients greater than 60 years of age were treated with a combination therapy including cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone (VNCOP-B). Complete remission (CR) was achieved by 202 (58%) patients and partial remission (PR) by 87 (25%), whereas the remaining 61 (17%) patients were nonresponders. The overall response rate (CR + PR) was 83%. Clinical and hematologic toxicities were modest, because 71% of the patients received granulocyte colony-stimulating factor (G-CSF). The CR rates for the three age groups (60 to 69, 70 to 79, and >/=80 years) were similar: 61%, 59%, and 56%, respectively. At 5 years, the relapse-free survival rate was 65%, the overall survival rate was 49%, and the failure-free survival rate was 33%. In the multivariate analysis, prognostic factors associated with longer survival or longer relapse-free survival turned out to be localized disease stage (P =.001) and good performance status (P =.0002). Application of the International Prognostic Factor Index was significantly associated with outcome (P =.001). These data confirm on a large cohort of patients that the VNCOP-B regimen is effective in inducing good CR and relapse-free survival rates with only moderate toxic effects in elderly aggressive-histology NHL.

Long-term Outcome of Autologous Hematopoietic Stem Cell Infusion in Cirrhosis: Waning Effect over Time.

Background and Aims: Long-term data on cell-based therapies, including hematopoietic stem cell infusion in cirrhosis, are sparse and lacking.Methods: Patients with cirrhosis of non-viral etiology received either standard-of-care (n = 23) or autologous CD34+ cell infusion through the hepatic artery (n = 22). Study patients received granulocyte colony-stimulating factor (commonly known as G-CSF) injections at 520 µgm per day for 3 days, followed by leukapheresis and CD34+ cell infusion into the hepatic artery. The Control group received standard-of-care treatment.Results: Mean CD34+ cell count on the third day of G-CSF injection was 27.00 ± 20.43 cells/µL 81.84 ± 11.99 viability and purity of 80-90%. Significant improvement in the model of end-stage liver disease (commonly known as MELD) score (15.75 ± 5.13 vs. 19.94 ± 6.68, p = 0.04) was noted at end of 3 months and 1 year (15.5 ± 5.3 vs. 19.8 ± 6.4, p = 0.04) but was not statistically different at end of the second (17.2 ± 5.5 vs. 20.3 ± 6.8, p = 0.17) and third-year (18.4 ± 6.1 vs. 21.3 ± 6.4, p = 0.25). No difference in mortality (6/23 vs. 5/23) was noted.Conclusions: Autologous CD34+ cell infusion effectively improved liver function and MELD score up to 1 year but the sustained benefit was not maintained at the end of 3 years, possibly due to ongoing progression of the underlying disease.

Unmanipulated haploidentical hematopoietic stem cell transplantation for children with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders and is rare in children. Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used in children with MDS with excess blasts and in patients with refractory cytopenia of childhood (RCC) associated with monosomy 7, complex karyotype, severe neutropenia, or transfusion dependence. We recruited27 children with MDS who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT). At transplantation, 10 patients had RCC, 12 patients had advanced MDS (RAEB and RAEB-T), and 5 patients had myelodysplasia-related acute myeloid leukemia (MDR-AML). All patients received granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow cells and peripheral blood stem cells. At a median follow-up of 24.1months (range: 2.0-74.5months) after HSCT, the estimated probabilities of 3-year disease-free survival (DFS) and overall survival (OS) were both 81.9% (95% CI, 66.8-100.0%). The estimated 3-year incidences of relapse (CIR) and non-relapse mortality (NRM) were both 7.4% (95% CI, 1.2%-21.4%). The 100-day cumulative incidence of grade II-IV aGVHD was 52.6% (95% CI, 42.9-62.3%), while that of grade III-IV aGVHD was 11.1% (95% CI, 5.1-17.1%). The 3-year cumulative incidences of overall and extensive cGVHD were 42.3% (95% CI, 19.8%-57.5%) and 21.1% (95% CI, 2.5%-63.2%), respectively. Univariate analysis showed that chronic GVHD significantly affected OS and DFS. Haploidentical HSCT may be an effective treatment option with easier donor availability for pediatric patients with MDS.

Yf-H-2015005, a New CXCR4 Antagonist, in the Mobilization of Hematopoietic Stem Cells in Patients with Non-Hodgkin Lymphoma: A Randomized-Controlled Phase 3 Study

Background: Autologous hematopoietic stem cell transplantation (AHSCT) is an important therapy for non-Hodgkin's lymphoma (NHL). This study evaluated the safety and efficacy of YF-H-2015005, a new CXCR4 antagonist, when used to mobilize hematopoietic stem cells in patients with NHL eligible for treatment with AHSCT. Methods: This phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study enrolled patients (age range, 18 to 65 years) with NHL, and who were in their first or second complete or partial remission. The patients received granulocyte colony-stimulating factor (G-CSF, 10 mg/kg/day) each morning for up to 8 days. Treatment with YF-H-2015005 (0.24 mg/kg/day) or placebo was initialed during the evening of the fourth day of G-CSF administration, and then continued for up to 4 days. Starting on day 5, apheresis was performed for 9 to 10 hours after each dose of YF-H-2015005 or until ≥ 5 × 106 CD34+ cells/kg had been collected. The primary endpoint was the percentage of patients who collected ≥ 5 × 106 CD34+ cells/kg during the course of 4 or fewer apheresis days. The secondary endpoints were the percentage of patients who collected ≥ 2 × 106 CD34+ cells/kg during the course of 4 or fewer apheresis days, the number of apheresis days required to reach ≥ 2 × 106 CD34+ cells/kg, the number of apheresis days required to reach ≥ 5 × 106 CD34+ cells/kg, and patient safety. Results: A total of 101 patients with NHL were randomly assigned to the YF-H-2015005 group (n = 51or placebo group (n = 50), respectively. The percentage of patients who met the primary endpoint was 57% (29/51) in the YF-H-2015005 group and 12% (6/50) in the placebo group (P &amp;lt; 0.001). A larger proportion of patients in the YF-H-2015005 group (86%) achieved the secondary endpoint of collecting ≥ 2 × 106 CD34+ cells/kg in 4 or fewer apheresis days when compared with the placebo group (38%, P &amp;lt; 0.001). Patients in the YF-H-2015005 group required shorter time periods to collect ≥ 2 × 106 CD34+ cells/kg (1 days vs. 4 days) and ≥ 5 × 106 CD34+ cells/kg (3 days vs. not reached). Treatment-related adverse event were observed in 37 patients (20 in the YF-H-2015005 group and 17 in the placebo group). The most common adverse events in the YF-H-2015005 group were diarrhea (14%), hyperhidrosis(6%), elevated alkaline phosphatase (6%). No serious treatment-related adverse event occurred. Conclusions: The combination of YF-H-2015005 and G-CSF was a tolerable regimen for use in rapidly mobilizing and collecting CD34+ cells for transplantation in patients with NHL. Disclosures Zhu: Mundipharma: Research Funding.

Stem Cell Therapy for Cirrhosis of Liver in Bangladesh: Specific Design Compatible for Developing Country.

Aims and objectivesTo assess the safety and efficacy of stem cell therapy in patients with cirrhosis of the liver (LC) in the context of developing country with limited facilities for cell-based therapy and advanced technologies.Materials and methodsA total of 34 patients received granulocyte colony-stimulating factor at a dose of 30 IU, daily for 2 to 11 days to upregulate the numbers of white blood cells and stem cells. Subsequently, stem cells were isolated from the peripheral blood of LC patients in a closed chamber using a harvesting machine. Variable amounts of autologous stem cells were injected to LC patients for once. The patients were followed for 3 months and various factors related to safety and parameters of efficacy were analyzed in this interim report.ResultsOut of 34 patients available for final analysis, 3 months after the start of stem therapy, 4 patients died within this period. There was no significant alteration in biochemical parameters due to stem cell therapy, and patients also did not develop any features of acute liver failure indicating that short-term safety parameters of stem cell therapy may be acceptable. Stem cell therapy had a dominant effect on ascites of in this cohort. Although 24 of 34 patients had ascites at the start of therapy,ascites were found in 11 patients after one month and only 4 patients had ascites after 3 months. The positive role of stem cell therapy on ascites in LC patients may be attributed, even in part, to increased serum levels of albumin after therapy compared to basal levels (p <0.001).ConclusionThis first study about stem cell therapy in Bangladesh indicates that cell therapy may be accomplished in general hospitals of developing countries if the proper design and mild to moderate types of invasive approach is utilized. The apparent safety of administered stem cells in LC patients and the observed effect on ascites of LC patients inspire optimism about the installation of new and innovative therapy in Bangladesh. Future studies with phase I/II may with stem cell and others cell may be planned at Bangladesh in patients with LC and other intractable diseases with suitable control arms.How to cite this article: Mahtab MA, Akbar SMF, Begum M, Islam MA, Rahim MA, Noor-E-Alam SM, Alam MA, Khondaker FA, Moben AL, Mohsena M, Khan SI, Huq MZ, Munshi S, Hoque A, Haque SA. Stem Cell Therapy for Cirrhosis of Liver in Bangladesh: Specific Design Compatible for Developing Country. Euroasian J Hepatogastroenterol, 2018;8(2):121-125.

Multicenter Phase 2 Study of Reduced-Dose CHOP Chemotherapy Combined With Rituximab for Elderly Patients With Diffuse Large B-Cell Lymphoma

IntroductionElderly patients are more prone to encounter some adverse factors when they receive chemotherapy compared to younger patients. Addition of rituximab to a reduced dose (RD) of cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy might improve patient outcomes with an improved toxicity profile when provided to elderly patients with diffuse large B-cell lymphoma. Patients and MethodsA total of 53 patients aged ≥ 65 years with diffuse large B-cell lymphoma diagnosed between August 2012 and December 2014 were enrolled onto this study. RD-R-CHOP regimen consisted of rituximab at 375 mg/m2, cyclophosphamide at 600 mg/m2, doxorubicin at 30 mg/m2, and vincristine at 1 mg on day 1 of each cycle and 40 mg of prednisone on days 1 to 5. Patients received granulocyte colony-stimulating factor if they experienced grade 3/4 neutropenia or febrile neutropenia during any cycle. ResultsThe median follow-up duration was 18 months (range, 1-44 months). Complete response and overall response rates were 64.1% and 81.1%, respectively. Three-year event-free and overall survival rates were 45.7% ± 8.4% and 62.7% ± 8.1%, respectively. Grade 3/4 neutropenia occurred in 20 patients (37.7%), while febrile neutropenia occurred in 7 patients (20.7%). ConclusionOutcomes of RD-R-CHOP chemotherapy were comparable to those of standard-dose R-CHOP or previous dose-adjusted R-CHOP chemotherapy. In the future, strategies such as tailored therapy based on geriatric assessment results are needed to determine the chemotherapeutic dosage.

Increase in short-term risk of rejection in heart transplant patients receiving granulocyte colony-stimulating factor.

Neutropenia is a significant adverse event after heart transplantation (HT) and increases infection risk. Granulocyte colony-stimulating factor (G-CSF) is commonly used in patients with neutropenia. In this work, we assessed the adverse effects of G-CSF treatment in the setting of a university hospital. Data on HT patients from January 2008 to July 2016 were reviewed. Patients who received G-CSF were identified and compared with patients without a history of therapy. Baseline characteristics, rejection episodes, and outcomes were collected. Data were analyzed by incidence rates, time to rejection and survival were analyzed using Kaplan-Meier curves, and odds ratios were generated using logistic regression analysis. Two hundred twenty-two HT patients were studied and 40 (18%) received G-CSF for a total of 85 total neutropenic events (0.79 event/patient year). There were no differences in baseline characteristics between the groups. In the 3 months after G-CSF, the incidence rate of rejection was 0.067 event/month. In all other time periods considered free of G-CSF effect, the incidence rate was 0.011 event/month. This rate was similar to the overall incidence rate in the non-GCSF group, which was 0.010 event/month. There was a significant difference between the incidence rates in the G-CSF group at 0 to 3 months after G-CSF administration and the non-GCSF group (p = 0.04), but not for the other time periods (p = 0.5). Freedom from rejection in the 3 months after G-CSF administration was 87.5% compared with 97.5% in the non-GCSF group (p = 0.006). G-CSF administration was found to be associated with significant short-term risk of rejection. This suggests the need for increased surveillance during this time period.

Post-Transplant Cyclophosphamide as Sole Graft-versus-Host Disease Prophylaxis Is Feasible in Patients Undergoing Peripheral Blood Stem Cell Transplantation for Severe Aplastic Anemia Using Matched Sibling Donors

High-dose cyclophosphamide (PTCY) after allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) after HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor–mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation. Thirty patients with a median age of 29 years (range, 16 to 49) were enrolled in this study. Engraftment was seen in 27 patients (90%) at a median of 16 days (range, 12 to 21) post-HSCT. None of the patients developed veno-occlusive disease of the liver or hemorrhagic cystitis. Grades II to IV acute GVHD was seen in 22% of patients with grades III to IV GVHD in 11.1%. The 2-year cumulative incidence of chronic GVHD was 22.7%. Fourteen patients (46.6%) did not require any further immunosuppression after receiving PTCY. Comparing with 2 historical cohorts of 30 patients each who received cyclosporine and methotrexate (MTX; at 15 mg/m2 [MTX15] and 10 mg/m2 [MTX10]), the incidence of grades II to IV acute GVHD was lower, albeit not significantly, with the use of PTCY (PTCY, 22.2%, vs MTX15, 37.1%, vs MTX10, 53.8%; P = .056), whereas rates of chronic GVHD were significantly reduced (PTCY, 22.7%, vs MTX15, 63.6%, vs MTX10, 76.2%; P = .013). Viral infections including cytomegalovirus were significantly higher with the use of PTCY (60%) compared with cyclosporine and MTX (MTX15, 23.3%, vs MTX10, 33.3%; P = .008). Overall survival was similar between the 3 groups. We conclude that PTCY as the sole GVHD prophylaxis is associated with low rates of acute and chronic GVHD in patients undergoing PBSC transplant for SAA using HLA-matched donors. This trial is registered at CTRI/2010/091/001480.

Use of prophylactic growth factors and antimicrobials in elderly patients with cancer: a review of the Medicare database

Growth factors and antimicrobials can reduce complications of chemotherapy-induced myelosuppression. Their prophylactic use in elderly patients is important given the associated comorbidity in this age group. There is a developing trend by payers to include supportive care agents in chemotherapy care bundles, which could affect clinical practice. We examined whether the febrile neutropenia (FN) risk categories can be used to describe utilization in the Centers for Medicare & Medicaid fee-for-service system in older adults. We conducted a retrospective cohort study using the Medicare 20% sample data to describe growth factor and antimicrobial use patterns in patients receiving chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL). The highest percentage of patients receiving granulocyte colony-stimulating factor (GCSF) within the first 5days of a chemotherapy cycle were on high-FN-risk regimens, particularly for cycle 1 (73.7%, breast cancer; 61.5%, NHL) and cycle 2 (75.9%, breast cancer; 77.5%, NHL). Chemotherapy regimens for lung cancer are less myelotoxic, and growth factor use was more likely with latter cycles. Antibiotic use was lower at 15% within a cycle and appeared to be in response to complications. Practitioners use GCSF and antibiotics for elderly patients treated with potentially toxic chemotherapy, while comorbidity burden plays a role for patients treated with less myelotoxic regimens. The complexity of these choices in clinical practice should be considered in the proposed reimbursement changes being piloted by Medicare and private insurance companies seeking treatment cost reductions, as altered use could affect safety and efficacy.

Retrospective Study of the Optimal CHOP Dose for Elderly Patients with Diffuse Large B-Cell Lymphoma

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma, and the number of elderly patients with DLBCL is increasing. While rituximab plus CHOP (R-CHOP) therapy is considered as the standard first-line treatment for DLBCL, elderly patients are often frail and unable to tolerate the standard dose of R-CHOP. Fifteen years ago, we conducted a prospective study to investigate optimal reduced doses of CHOP therapy for patients aged 65-79 years and those older than 79 years. We concluded that 5/6 (83%) and 7/12 (58%) doses of standard CHOP are effective and tolerable for these two age groups, respectively (Mori M, et al. Leuk Lymphoma. 2001;41:359-66). Since then, we have applied this strategy with the standard dose of rituximab. To evaluate the efficacy and tolerability of reduced R-CHOP therapy for elderly patients, we performed a retrospective analysis.Methods: We reviewed medical records of patients aged 65 years or older with newly diagnosed DLBCL, who underwent R-CHOP therapy from August 2010 to December 2013. Intravascular large B-cell lymphoma and primary central nervous system lymphoma were excluded from this study because R-CHOP therapy alone is not considered as standard for these diseases. We calculated the relative dose intensity (RDI), dividing the actually used doses of cyclophosphamide and doxorubicin by the interval between each course compared with the standard doses (750 mg/m2 cyclophosphamide and 50 mg/m2 doxorubicin every 21 days).Results: During the study period, data were collected from 100 patients (56 males and 44 females) with a median age of 74 (65-86) years. Sixty patients had advanced stages, 40 patients had a score of at least one in the Charlson comorbidity index (Charlson ME, et al. J Chronic Dis. 1987;40:373-83), 18 patients had a poor performance status (Eastern Cooperative Oncology Group performance status: ≥2), and 14 patients were older than 79 years. The overall response rate was 93%, and the complete response (CR) rate was 81%. Three-year overall survival (3-yr OS) was 78%. In comparison with the international prognostic index (IPI), 3-yr OS was 100% (IPI: low, n=26), 94% (IPI: low-intermediate, n=17), 71% (IPI: high-intermediate, n=24), and 58% (IPI: high, n=33). Hematologically adverse events were generally tolerable. No patient experienced a grade 4 hemoglobin decrease, and only four patients experienced a grade 4 platelet decrease. Although 55 patients received granulocyte colony-stimulating factor, a grade 4 leukocyte decrease was common (n=38) and febrile neutropenia (FN) was often seen (n=21). Patients who experienced FN had a significantly shorter OS (p=0.04). With a median follow up of 44.4 months, 20 patients experienced disease progression and 15 patients died after progression. Five patients remained in CR but died of other types of cancer. The other seven patients died of other causes. The median RDI was 0.81 in patients aged 65-79 years and 0.58 in patients older than 79 years. These doses were very similar to the originally intended doses of 5/6 (0.83) for younger patients and 7/12 (0.58) for older patients. The older group tended to show shorter OS (3-yr OS: 64%). However, recurrence rates of the two groups were very similar.Conclusions: This study demonstrates that rituximab plus 5/6 or 7/12 doses of CHOP therapy are effective and tolerable for elderly patients aged 65-79 years and those older than 79 years, respectively. It is noteworthy that the prognosis of patients with an IPI score of ≤2 was very satisfactory. Based on these results, the dose intensity does not have to be increased for these low risk groups. It is possible that increasing the dose intensity in high risk (IPI score: ≥3) patients improves the outcome. However, high risk patients tend to have much tumor burden and a poor performance status. In this group, higher dose chemotherapy will also increase the risk of developing FN and might be associated with inferior OS. Treatment of frail elderly patients with high-risk DLBCL is extremely challenging, and we need to gain further experience. DisclosuresNo relevant conflicts of interest to declare.

Severe exacerbation of relapsing-remitting multiple sclerosis after G-CSF therapy.

A 31-year-old woman (figure) with relapsing-remitting multiple sclerosis (MS) (first symptoms February 1994, first diagnosis August 1994, Expanded Disability Status Scale [EDSS] 3.0) was diagnosed with breast cancer in January 2014. The last relapse had occurred in August 2007. Under treatment with natalizumab from August 2007 to June 2013, the patient was clinically stable and the brain MRI showed no signs of disease activity. Because of a positive JC virus antibody test, the immunomodulatory therapy was changed to fingolimod in July 2013. The patient remained clinically stable during the switching period and thereafter. In January 2014, a brain MRI showed 2 new lesions without contrast enhancement. After diagnosis of breast cancer in January 2014 and subsequent surgery in February 2014, adjuvant chemotherapy with cyclophosphamide, doxorubicin, and docetaxel was started (March–July 2014). Fingolimod was stopped in March 2014 considering the strong immunosuppressive effect of cyclophosphamide. The patient received granulocyte colony-stimulating factor (G-CSF; pegfilgrastim) 6 mg subcutaneously at each of the 6 cycles of chemotherapy to reduce the risk of infection during the phase of chemotherapy-induced neutropenia. In July 2014, the patient experienced a numbness and tingling in her right leg, which progressed to a severe hemiparesis (EDSS 7.0) leading to hospitalization. The MRI scan of the brain revealed several new lesions including a lesion with contrast enhancement. An IV steroid pulse therapy was administered. She recovered partially (EDSS 6.5). Fingolimod was started again in August 2014. Subsequently the patient developed another relapse with a worsening of the atactic hemiparesis on the left side, resulting in an inability to walk (EDSS 7.5). Again an IV steroid pulse therapy was administered. The patient recovered partially until the end of August 2014, when she was discharged from rehabilitation. At that time, she was able to walk for 50 meters without aid (EDSS 6.0). Another brain MRI in September 2014 revealed confluent progressive lesions in the white matter with partial contrast enhancement. The patient was referred to our inpatient clinic, where again a steroid pulse therapy was administered. In the following months, the patient recovered to a clinical condition similar to that before the start of the chemotherapy (as of August 2015, EDSS 3.0). An MRI scan of the brain in September 2015 did not show new lesions or contrast enhancement compared to the preceding MRI examination in September 2014.

Four Cases of Successful Treatment after Podostroma Cornu-Damae Intoxication

Four individuals mistook Podostroma cornu-damae for Cordyceps sobolifera and reported diarrhoea and vomiting after consuming the toxic mushroom. All symptoms resolved within four days. However, leukocytopenia, thrombocytopenia, depilation, and desquamation appeared later, and one patient was diagnosed with sepsis. All patients received granulocyte colony-stimulating factor and blood transfusions in an isolated aseptic room, and they recovered without complications. Podostroma cornu-damae is a poisonous mushroom containing trichothecene. This mushroom is not well known and is easy to be mistaken for the more common Cordyceps sobolifera sold as a healthy food in East Asia. Podostroma cornu-damae intoxication has characteristic early and delayed symptoms. Early symptoms are mainly gastrointestinal, while delayed symptoms are caused by inhibition of cellular division causing pancytopenia and can lead to death. A case series of Podostroma cornu-damae poisoning was presented, including one complicated case complicated with life-threatening sepsis.

Difficulties in hematopoietic progenitor cell collection from a patient with TEMPI syndrome and severe iatrogenic iron deficiency

Collection of hematopoietic progenitor cells by apheresis (HPC-A) requires separation of cells by density. Previous studies highlighted the challenges of HPC-A collection from patients with abnormal red blood cells (RBCs). TEMPI syndrome is a recently described condition defined by teleangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. Patients with TEMPI syndrome have responded to therapies used to treat plasma cell dyscrasias and may benefit from autologous HPC transplantation. We report HPC-A collection from a patient with TEMPI syndrome that was complicated by severe iron deficiency. The patient received granulocyte-colony-stimulating factor (G-CSF) and plerixafor for HPC mobilization and underwent 3 days of HPC-A collection. The patient presented for collection with a microcytic erythrocytosis. Over 3 days, approximately 50 L of whole blood was processed, and 2 × 10(8) CD34+ cells were collected (2.8 × 10(6) CD34+ cells/kg). The mean collection efficiency (CE), percentage of mononuclear cells, hematocrit (Hct), and RBC count were 18%, 90%, 14%, and 9 × 10(11) , respectively. Altering collection variables to avoid RBC contamination reduced CE. Ficoll preparations of the products after freeze-thaw showed RBC contamination and hemolysis. Postthaw viability exceeded 95%. The products were not RBC reduced or washed. There were no adverse reactions during or after infusion. HPC-A collection from a patient with TEMPI syndrome was complicated by microcytic erythrocytosis, leading to RBC contamination and hemolysis in the product. Adequate HPCs were collected and the patient tolerated infusion without RBC depletion or washing. Our report highlights difficulties of HPC-A collection from iron-deficient patients.

Rituximab-associated agranulocytosis in children with refractory idiopathic nephrotic syndrome: case series and review of literature.

Agranulocytosis has been reported as a delayed-onset complication of rituximab treatment. However, the exact incidence and risk factors of this complication in patients with nephrotic syndrome remain unknown. Records of 213 rituximab treatments for 114 patients with refractory nephrotic syndrome between February 2006 and April 2013 were reviewed to identify episodes of agranulocytosis (defined as an absolute neutrophil count of <500 mm(3)). Eleven episodes of agranulocytosis were detected in 11 patients. Median time of onset of agranulocytosis was 66 days (range, 54-161 days) after rituximab treatment. Nine patients experienced acute infections and received antibiotics. All but one patient received granulocyte colony-stimulating factor. Agranulocytosis resolved in all cases within a median of 3 days. The incidence of agranulocytosis was 9.6% in total patients and 5.2% in all treatments. Median age of the 11 patients who developed agranulocytosis was 6.4 years at the first rituximab treatment, significantly younger than the median age of the 103 patients who did not (median, 12.5 years; P = 0.0009). Five patients received re-treatment with rituximab. No recurrence of agranulocytosis was observed in any patient. It is important to pay extra attention to this clinically serious delayed-onset complication as it may be accompanied by life-threatening infections such as sepsis. Further clinical studies are needed to clarify its pathogenesis.

The Use Of Simple Patient Blood Management Strategies As An Alternative To Platelet and Red Cell Transfusion In Autologous Stem Cell Transplant

▪ IntroductionHigh dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is considered the standard of care for patients with high-risk or relapsed lymphoma and multiple myeloma (MM). With most patients requiring both red cell transfusion ,and platelet support until marrow engraftment. Jehovah's Witnesses (JW), based on religious convictions, refuse blood products, and therefore are frequently denied transplants in most centers, due to the presumed fear of death from bleeding and anemia.We present a series of 119 JW diagnosed with lymphoma (n= 54), (MM) (n= 63) and amyloidosis (n=2) who received treatment with HDC and ASCT without transfusion support. MethodsAll JW undergoing HDC and ASCT at Pennsylvania Hospital between May 1996 and March 2013 were included. Patients were primed pre-transplant with IV iron and erythropoietin to a target Hemoglobin (Hb) > 11g/dl.Cryopreservation of collected cells, was performed using normal saline and albumin instead of fresh frozen plasma. Post apheresis, HDC was delayed to allow Hb levels to rise to ≥ 11 g/dl and platelets ≥100,000. Post-transplant, patients received granulocyte colony-stimulating factor, erythropoietin and initially interleukin-11 which was later discontinued, as there was no benefit observed in the length of time to platelet engraftment. Thrombocytopenia was managed with antifibrinolytic agents (Amicar) and vitamin K, the avoidance of anticoagulation and aspirin, and rarely cryoprecipitate, desmopressin, and nasal vasoconstrictors. ResultsEngraftment The median number of days to neutrophil engraftment, with absolute neutrophil count ≥1,000/μL, was 10.0 days. The median Hb at the onset of chemotherapy was 11.8 g/dL, (range 7-15.3 g/dL), and the average decrease in Hb was 5.0 g/dL, with an average nadir of 6.8 g/dL. The median number of days with Hb under 8 g/dL was 5.5 days. The median platelet count at onset of chemotherapy was 148 x 103/μL (range of 65 to 502 x 103/μL). The median number of days with a platelet count under 10 x 103/μL was 3.0 days (range 0 to 14 days) with a median platelet nadir of 4.0 x 103/μL (range 1-50 x 103/μL). Patients with lymphoma experienced a lower drop in Hb post cytotoxic regimen than myeloma patients (ΔHb = 4.5g/dl for MM, 6.0g/dl for lymphoma, p < 0.05).The average length of stay (LOS) was 19.0 days. Bleeding ComplicationsBleeding complications were classified using the WHO criteria. Patients with platelet counts greater than 5 x 103/μl experienced no bleeding complications or death due to hemorrhage. There was one grade 4 hemorrhage, a temporal infarct leading to temporary vision loss and confusion, one grade 3 hemorrhage, a major gastrointestinal bleed, and one grade 2 hemorrhage which was hematuria. Sixteen patients experienced grade 1 bleeding episodes consisting of subconjunctival hemorrhage (n=5), epistaxis (n=6), minor vaginal bleeding (n=2), minor oral bleeding (n=1) a thigh hematoma (n=1), and a minor retinal bleed (n=1). Cardiac ComplicationsForty two of the one hundred and nineteen patients who underwent HDC and ASCT, experienced cardiac complications.These included new onset arrhythmias (n=19), profound hypotension (n=15), congestive heart failure (n=10) and acute myocardial infarction (n=1). The mean Hb nadir for patients who experienced a cardiac complication was 6.6 g/dL .Additionally the median age was 56 years (range 21-71years) and the average change in hemoglobin was 5.0g/dl. MortalityThe 100 day transplant related mortality was 5%.The six deaths recorded were due to sepsis, multi-organ failure due to pancytopenia and cardiac events. ConclusionBased on our study we conclude that HDC followed by ASCT, can safely be performed without the need for transfusion support, with low mortality rates and low incidences of major bleeding complications .Anticipated anemia may be managed by ensuring priming of Hb with the use of IV iron and erythropoietin to Hb ≥11 g/dl, and simple patient blood management techniques.Thrombocytopenia may be managed similarly, by allowing platelet recovery post apheresis to ≥ 100, 000. We also believe that Amicar and Vitamin K offer as good and effective, an alternative to prophylactic platelet transfusion in the management of thrombocytopenia. Additionally these agents may be used to achieve homeostasis in patients who develop platelet refractoriness, and similarly the use in all transplant patients may be appropriate. Disclosures:No relevant conflicts of interest to declare.