Time Of Absolute Neutrophil Count Research Articles

Quantification of Radiation Injury on Neutropenia and the Link between Absolute Neutrophil Count Time Course and Overall Survival in Nonhuman Primates Treated with G-CSF

PurposeTo model absolute neutrophil count (ANC) suppression in response to acute radiation (AR) exposure and evaluate ANC time course as a predictor of overall survival (OS) in response to AR exposure with or without treatment with granulocyte colony-stimulating factor in nonhuman primates.MethodsSource data were obtained from two pivotal studies conducted in rhesus macaques exposed to 750 cGy of whole body irradiation on day 0 that received either placebo, daily filgrastim, or pegfilgrastim (days 1 and 8 after irradiation). Animals were observed for 60 days with ANC measured every 1 to 2 days. The population model of ANC response to AR and the link between observed ANC time course and OS consisted of three submodels characterizing injury due to radiation, granulopoiesis, and a time-to-event model of OS.ResultsThe ANC response model accurately described the effects of AR exposure on the duration of neutropenia. ANC was a valid surrogate for survival because it explained 76% (95% CI, 41%–97%) and 73.2% (95% CI, 38.7%–99.9%) of the treatment effect for filgrastim and pegfilgrastim, respectively.ConclusionThe current model linking radiation injury to neutropenia and ANC time course to OS can be used as a basis for translating these effects to humans.

Efficacy Analysis of Unrelated Cord Blood Transplantation for High-Risk Refractory AML1-ETO Positive Myeloid Leukemia

To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×107/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×105/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×109/L and platelet 20×109/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.

A case of engraftment syndrome in the medical intensive care unit

Engraftment syndrome (ES) is an increasingly diagnosed complication after hematopoietic cell transplantation (HCT). Clinical presentation most commonly includes, but is not limited to fever, diarrhea, and skin rash developing at the time of absolute neutrophil count (ANC) recovery. Due to the broad and pleiotropic clinical presentation, ES can be a challenging diagnosis. Furthermore, despite many reports about the presentation of ES, the syndrome is still not completely understood. While most presentations of ES are mild and can either resolve spontaneously or with a brief course of systemic corticosteroids, mortality rates ranging from 8%-18% have been described. We present a case of ES in a critical care setting. A male patient who had an allogeneic HCT and developed fevers, diffuse skin rash, acute kidney injury and hypoxemic respiratory failure after his absolute neutrophilic count started recovering from nadir. He was subsequently transferred to the medical intensive care unit (MICU) for further management, where he was initially managed with mechanical ventilation, vasopressors and antibiotics. An extensive workup that included bronchoscopy with bronchoalveolar lavage was performed and failed to show an infectious etiology. Due to concern for ES, patient was started on steroids and his clinical status dramatically improved. The patient was eventually extubated and transferred back to the floor in stable condition. It is important for internists and critical care physicians in the MICU to be aware of post-HCT complications and be cognizant of the clinical signs of ES to better understand the syndrome and its management.

Therapeutic Efficacy Analysis of Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for 14 Adult Patients with T Lymphoblastic Lymphoma

To investigate the therapeutic efficacy of allogeneic peripheral blood hematopoietic stem cell transpdantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL). The clinical data of 14 adult patients with T-LBL treated with allo-HSCT were collected, the hematopoietic reconstruction, survival and relapse, as well as overall survival (OS) rate, event-free survival (EFS) rate of 1, 3 and 5 years were analysed retrospectively. All the patients were engrafted with neutrophil successfully, the median time of absolute neutrophil count >0.5 × 10(9)/L was 13 (10-19) d; 13 patients were engrafted with platelets successfully, the median time of Plt count >20 × 10(9)/L was 17 (12-62) days. The acute GVHD occurred in 6 patients, but among them only 1 case with 3 grade of aGVHD; out of 14 patients, 5 developed chronic GVHD. The transplant-related mortality at 100 days was 7.1% (1/14), mainly from coronary heart disease and pulmonary infection. The median follow-up time was 26.5 months, the estimated 1, 3 and 5 year OS rate was 85.7%, 47.6% and 38.1%, respectively, and estimated 1, 3 year EFS rate was 85.7%, 34.4% and 34.1%, respectively. The relapse rate was 42.8% (6/14) and the median relapse time was 22.5% months after transplantation. Up to now, 7 patients still survive, 1 patient out of them have survived for 103 months. The allo-HSCT is a safe and effective method for treatment of T-LBL.

非亲缘脐血造血干细胞移植成功治疗WAS综合征2例报告

目的：探讨非亲缘脐血干细胞移植术治疗Wiskott-Aldrich综合(Wiskott-Aldrich Syndrome, WAS)的临床疗效。方法：2例通过基因检测诊断的WAS综合征的患儿进行了非亲缘脐血干细胞移植术。预处理方案采用环磷酰胺、白消安、氟达拉滨、塞替派。预防移植物抗宿主病采用环孢素A、骁悉、甲氨蝶呤。输注有核细胞数分别为7.8 × 107/kg、6.67 × 107/kg；CD34+细胞数分别为8.32 × 104/kg、6.67 × 104/kg。结果：中性粒细胞绝对数 > 0.5 × 109/L的天数分别为15、33天，未输注情况下，血小板 > 20 × 109/L的天数为移植后30、45天，移植后28 d采用短串重复序列聚合酶链反应查植入证据均为供者独立植入。结论：非亲缘脐血造血干细胞移植可以有效治疗WAS综合征。 Purpose: To explore the clinical efficacy of unrelated umbilical cord blood stem cell transplantation for Wiskott-Aldrich syndrome. Method: Two patients were diagnosed with Wiskott-Aldrich syndrome by gene detection and received transplantation form unrelated umbilical cord blood stem cell. Two patients received a myelieblast conditioning with Cyclophosphamide, Busulfan, Fludarabine, Thiotepa. Cyclosporine A, Mycophenolate mofetil and Methotrexate were given to prophylaxis of graft versus host disease (GVHD). The doses of infused total nucleated cell (TNC) of two patients were 7.8 × 107/kg and 6.67 × 107/kg, respectively. The two patients’ CD34+ cells numbers were 8.32 × 104/kg and 6.67 × 104/kg, respectively. Result: The two patients had a successful engraftment, with 100% donor-derived cells by day 28 after transplantation. The time of absolute neutrophil count (ANC) > 0.5 × 109/L of two patients was 15 and 30 days, respectively. The time of platelet count > 20 × 109/L without transfusion was 30 and 45 days, respectively. Conclusion: The transplantation of umbilical cord blood stem cell from unrelated donor appears to be a feasible and effective strategy for further optimizing the outcome of HSCT for Wiskott-Aldrich syndrome.

HSCT Improve Long-Term Outcome for Patients with T-Cell Lymphoma / Leukemia (TCL)

Objective To evaluate the treatment outcomes of hematopoietic stem cell transplantation (HSCT) in patients with T-cell lymphom / leukemia (TCL),observe hematopoietic reconstitution and transplant-related complications.Methods Seventeen TCL patients received HSCT from 2005 to 2013 in our hospital were retrospectively analyzed.Of the 17 patients,6 were T lymphoblastic lymphoma / leukemia (T-LBL),3 were Peripheral T-cell lymphoma / leukemia (PTL),2 were Anaplastic large cell lymphoma (ALCL),2 were Extranodal NK / T-cell lymphoma (NK / TCL),1 were Angioimmunoblastic T-cell lymphoma (ATCL) and 3 were Acute T lymphoblastic leukemia (T-ALL) with a median age of 35(19~67) years old.Ratio of male to female is 13F4. The distribution of stages was 2(14.2%),0(0%)and 12(85.7%) patients with stages II,III,and IV,respectively. The distribution according to international prognostic index (IPI) was 8(57.1%) patients in 2 score,1(7.1%) in 3 scores and 5 (35.7%) in 4 scores.Results ‡@17 patients were successfully engrafted, the median time of absolute neutrophil count(ANC) > 0.5×109/L was 11(8~15) days, the median time of platelet > 20×109/L was 13(8~18) days. 3 cases developed I degree acute GVHD, all patients were improved after treatment. ‡AAt a median follow-up of 36 (range,12-96) months,12 patients were alive and 5 relapsed and died from TCL after ASCT. The estimated 5-year probability of DFS and OS was (72.1±15.2)% and (59.7±15.2)% for all the patients.Conclusion The results showed that HSCT may significantly improve long-term outcome for patients with T-cell lymphoma / leukemia (TCL). DisclosuresNo relevant conflicts of interest to declare.

Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy

Biosimilars of filgrastim are in widespread clinical use in Europe. This phase III study compares biosimilar filgrastim (EP2006), with the US-licensed reference product, Neupogen(®), in breast cancer patients receiving (neo)adjuvant myelosuppressive chemotherapy (TAC). A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomized 1:1:1:1 into four arms. Two arms received only one product (nonalternating), biosimilar or reference, and two arms (alternating) received alternating treatments during each cycle (biosimilar then reference or vice versa). The primary end point was duration of severe neutropenia (DSN) during cycle 1. The baseline characteristics were balanced between the four treatment arms. Noninferiority of biosimilar versus the reference was demonstrated: DSN (days) in cycle 1 was 1.17 ± 1.11 (biosimilar, N = 101) and 1.20 ± 1.02 (reference, N = 103), 97.5% confidence interval lower boundary for the difference was -0.26 days (above the predefined limit of -1 day). No clinically meaningful differences were observed regarding any other efficacy parameter: incidence of febrile neutropenia (FN); hospitalization due to FN; incidence of infections; depth and time of absolute neutrophil count (ANC) nadir and time to ANC recovery during cycle 1 and across all cycles. The pattern and frequency of adverse events were similar across all treatments. This study demonstrates that biosimilar and the reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially benefiting public health by increasing access to filgrastim treatment. NCT01519700.

Unrelated umbilical cord blood transplantation with TBI/Ara-c/CY non-ATG conditioning regimen for adults with hematologic malignancies

To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) with improved myeloablative conditioning regimen (total body irradiation (TBI)/cytosine arabinoside (Ara-c)/cyclophosphamide (CY) without antithymocyte globulin (ATG)) in adult patients with hematological malignancies. Forty consecutive adult patients with hematological malignancies received improved myeloablative unrelated CBT at a single center from September 2006 to May 2011. Their average age was (23 ± 6) years and the average weight (58 ± 9) kg. Thirty-five (87.5%) patients were high-risk and 15 (37.5%) at the advanced disease status at pre-transplantation. They received 1 (n = 23) or 2 (n = 17) cord blood units. Seventy-five percent of them were transplanted with 1/2-human leukocyte antigen mismatched unit. The conditioning regimen consisted of 12 Gy TBI, granulocyte colony-stimulating factor (G-CSF) plus Ara-c and CY without ATG. All patients received a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD). For the entire group of patients, the average cell doses infused were (4.1 ± 1.1)×10⁷ total nucleated cells/kg and (2.4 ± 1.0)×10⁵ CD34(+) cells/kg. All patients acquired engraftment with an implantation rate of 100%. The average time of absolute neutrophil count (ANC) ≥ 0.5×10⁹/L was (20 ± 5) days and the average time of platelet ≥ 20×10⁹/L was(38 ± 12) days. Acute GVHD occurred in 23 patients (57.5%) and 4 (10.0%) were of grade III-IV. Chronic GVHD occurred in 22.9% (8/35) evaluable patients. Relapse occurred in 12.5% (5/40) patients. During a median follow-up period of 19.8 (range 4.6 - 55.0) months, the transplantation-related mortality was 15.0% (6/40) within 100 days and 35.0% (14/40) within 1 year. The main causes of mortality were pneumonia and severe acute GVHD. Two-year overall survival (OS) or disease-free survival was 58.8% and 58.8%, respectively. Two-year OS for patients with advanced or complete remission disease was 48.6% and 63.8%, respectively. The TBI/Ara-c/CY myeloablative conditioning regimen is well-tolerated and capable of establishing sustained donor cell engraftment and decreasing the risks of transplant-related death in adults with hematologic malignancies. For the high-risk and advanced patients, it may reduce the occurrences of relapse and chronic GVHD.

Outpatient consolidation chemotherapy in pediatric acute myeloid leukemia: a retrospective analysis

Background: To assess the outcomes of outpatient high dose cytosine arabinoside consolidation cycles in pediatric acute myeloid leukemia (AML) patients in comparison to inpatient treatment.Methods: We retrospectively analyzed 90 cycles of AML consolidation given to 30 patients between July 2003 and July 2007.Results: Median age was 8 years (range 1·5–15) and 22/30 (73·3%) were males. Sixty-nine of 90 (76·7%) cycles were given on an ambulatory basis; readmission occurred in 25/69 (36·2%) and there was one death. The outpatient cycles in comparison to the inpatient cycles required significantly fewer invasive blood investigations (p<0·001) but had comparable number of blood products administered as supportive therapy. There was no significant difference in the frequency of granulocyte colony stimulating factor usage and recovery time of absolute neutrophil count and platelet count. The incidence of febrile neutropenia though was comparable in the groups (72·5% outpatient versus 76·2% inpatient), but the duration (p=0·003) and subsequent therapeutic antifungal usage (p=0·001) was significantly more in inpatient administered cycles. Second line antibiotics were needed in 16/50 (32%) outpatient episodes of febrile neutropenia in contrast to 10/16 (72·5%) episodes of febrile neutropenia in inpatient courses (p=0·030).Conclusions: Outpatient AML consolidation therapy is safe and feasible in children. It appears to result in less frequent invasive blood studies; shorter duration of febrile neutropenia and consequently less antimicrobial and antifungal usage as compared to inpatient consolidation cycles. To our knowledge, this report is the first of its kind looking specifically at outpatient consolidation chemotherapy in AML.

246: Allogeneic blood and marrow transplantation in thalassemia major class 3: An experience of Iran

Objective: Our aim for this study was to describe the outcome of blood and marrow transplantation in patients with class 3 Thalassemia major. Methods: Since December 1992 till september 2006, fifty-two patients with Thalassemia class 3 received blood and marrow transplantation from their Human Leukocyte Antigen(HLA)-identical siblings. Thirty-two patients received bone marrow and twenty patients received peripheral blood stem cell transplantation. Conditioning regimen in 47 patients was Cyclophosphamide 40 mg/kg/day (from day–5 to -2) and Busulfan 3.5 mg/kg/day (from day –9 to -6) and in these patients Graft Versus Host Disease (GVHD) prophylaxis regimen was Cyclosporine.A (CY.A) 1.5mg/kg /day/IV (day–3), then 3mg/kg/day IV (days +7, +11), then 12.5 mg/kg/day/PO and Methotrexate 10mg/m2 (day +1), 6mg/m2(days +3, +6). Conditioning regimen in 5 patients was Fludarabin 40 mg/m2 (from –6 to –2) and Busulfan 4 mg/kg (from –5 to –2) and in this patients GVHD prophylaxis regimen was (CY.A) 3 mg/kg/day IV (days –3 and +7), then 12.5 mg/kg/day PO. Results: Median age at time of transplantation was 8.5 years (age range: 1-26), Male/Female: 21/31.Median time of absolute neutrophil count ≥ 0.5×109/L was +14 and Median time of platelet recovery ≥20×109/L was +25. At present 42 out of 52 are alive and 10 patients died due to acute GVHD, chronic GVHD, rejection, veno-occlusive disease, infection and the others. Thirty-four patients (64%) developed acute GVHD (grade I = 13, grade II = 7, grade III= 10, grade IV= 4). Three patients (5.8%) developed chronic GVHD (limited= 2, extensive= 1). 8-year disease free survival were 73.17%. 8-year overall survival were 79.85%. Conclusion: According to this study, for an acceptable outcome in Thalassemia class 3We need better conditioning and GVHD prophylaxis regimens to decrease cardiopulmonary and liver complications. The results of blood and marrow transplantation showed that it is better than supportive therapy such as transfusion and desferal therapy.

Allogeneic Hematopoietic Stem Cell Transplantation for Pesaro IIIβ-Thalassemia Major Using Fludarabine-Based Myeloablative or Non-Myeloablative Conditioning Regimen.

Objective : To explore the efficacy of Fludarabine-based myeloablative or non-myeloablative conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for classIII thalassemia major with regard to regimen toxicity, graft rejection, and disease-free survival (DFS).Methods: From June 2001 to October 2004, 8 patients underwent allo-HSCT in our BMT unit, including 5 male and 3 female, with median age 5 (3 ~ 19) years. Four patients received graft from sibling donor, including cord blood and peripheral blood stem cells, and the remaining 4 patients received graft from unrelated donors, including bone marrow and peripheral blood stem cells. Fludarabine (FDR) was added into the standard BU/CY regimen, consisting of FDR, BU, CY and ATG. Six patients received myeloablative stem cell transplantation and the remaining 2 patients with evidence of organ damage from iron-overload received nonmyeloablative unrelated donor stem cell transplantation. All patients received Cyclosporine A and Methotrexate for GVHD prophylaxis.Results: Eight patients were successfully engrafted with the median time of absolute neutrophil count (ANC) more than 0.5 ×109 /L was day +13 (+9 ~ +14), and the median time of platelet count more than 20 ×109 /L was day +25 (+8 ~ +39). Two patients died of grade IV aGVHD. The regimen-related toxicity (gradeImucositis, gradeII hemorrhagic cystitis, and gradeIhepatic toxicity) occurred in 3 patients. At a median follow up of 24 (8~48) months, the probability of DFS was 75%, including the two patients given nonmyeloablative stem cell transplantation from unrelated donor.Conclusion: Fludarabine-based conditioning regimen for allo-HSCT in Pesaro III thalassemia major was well tolerated, without increasing toxicity, and associated with durable engraftment and higher rate of DFS (75%). The successful transplantation from unrelated donors using nonmyeloablative conditioning showed that thalassemia clone can be eradicated by the reduced intensity HSCT, which relies upon immunosuppressive rather than myeloablative conditioning to facilitate engraftment of donor cells, and is a novel approach for the treatment of the patients with evidence of organ damage from iron-overload.

Allogeneic blood and marrow transplantation in thalassemia major class 3: an experience of Iran

Objective: Our aim for this study was to describe the outcome of blood and marrow transplantation in patients with class 3 thalassemia major. Method and patients: Since December 1992 till October 2002, forty-three patients with thalassemia class 3 received blood and marrow transplantation from their HLA-identical siblings. Median age at time of transplantation was 8 years (age range = 3–17), Male/Female = 24/19. Twenty-eight patients received bone marrow and fifteen patients received peripheral blood stem cell transplantation. Conditioning regimen was cyclophosphamide 40 mg/kg/day (from day–5 to -1) and busulfan 4 mg/kg/day (from day –9 to -6). GVHD prophylaxis regimen was cyclosporine A 3mg/kg /day/iv (from day −2 to +5) then 12.5 mg/kg/day/po (from day +5) and methotrexate 10mg/m2 (day +1), 6mg/m2 (days +3, +6). Results: Median time of absolute neutrophil count ≥ 0.5 × 109 /L was on day +20 and Median time of platelet recovery ≥20 × 109 /L was on day +25. At present 34 out of 43 are alive and 9 patients died due to aGVHD, cGVHD, rejection, veno-occlusive disease, infection and the others. Thirty-two patients (74.4%) developed aGVHD (grade I = 9, grade II = 7, grade III = 11, grade IV = 5). Seventeen patients (39.5%) developed cGVHD (limited = 5, extensive = 12). Eight year disease free survival in class 3 and 2 were 71% and 63%, respectively (p = 0.3).Eight year overall survival in class 3 and 2 were 78% and 79%, respectively (p = 0.00). Conclusion: According to this study, for an acceptable outcome in thalassemia class3. We need better conditioning and GVHD prophylaxis regimens to decrease cardiopulmonary and liver complications. The results of blood and marrow transplantation showed that it is better than supportive therapy such as transfusion and desferal therapy. Objective: Our aim for this study was to describe the outcome of blood and marrow transplantation in patients with class 3 thalassemia major. Method and patients: Since December 1992 till October 2002, forty-three patients with thalassemia class 3 received blood and marrow transplantation from their HLA-identical siblings. Median age at time of transplantation was 8 years (age range = 3–17), Male/Female = 24/19. Twenty-eight patients received bone marrow and fifteen patients received peripheral blood stem cell transplantation. Conditioning regimen was cyclophosphamide 40 mg/kg/day (from day–5 to -1) and busulfan 4 mg/kg/day (from day –9 to -6). GVHD prophylaxis regimen was cyclosporine A 3mg/kg /day/iv (from day −2 to +5) then 12.5 mg/kg/day/po (from day +5) and methotrexate 10mg/m2 (day +1), 6mg/m2 (days +3, +6). Results: Median time of absolute neutrophil count ≥ 0.5 × 109 /L was on day +20 and Median time of platelet recovery ≥20 × 109 /L was on day +25. At present 34 out of 43 are alive and 9 patients died due to aGVHD, cGVHD, rejection, veno-occlusive disease, infection and the others. Thirty-two patients (74.4%) developed aGVHD (grade I = 9, grade II = 7, grade III = 11, grade IV = 5). Seventeen patients (39.5%) developed cGVHD (limited = 5, extensive = 12). Eight year disease free survival in class 3 and 2 were 71% and 63%, respectively (p = 0.3).Eight year overall survival in class 3 and 2 were 78% and 79%, respectively (p = 0.00). Conclusion: According to this study, for an acceptable outcome in thalassemia class3. We need better conditioning and GVHD prophylaxis regimens to decrease cardiopulmonary and liver complications. The results of blood and marrow transplantation showed that it is better than supportive therapy such as transfusion and desferal therapy.