scholarly journals 577. Incidence and Outcomes of Positive Outpatient Surveillance Blood Cultures in Hematopoietic Stem Cell Transplant (HSCT) Patients with Graft Versus Host Disease (GvHD) On High Dose ≥ 0.5 mg/kg/day (HD) and Low Dose < 0.5mg/kg/day (LD) Steroid Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S353-S354
Author(s):  
Sarah Perreault ◽  
Molly Schiffer ◽  
Jennifer Zhao ◽  
Dayna McManus ◽  
Francine Foss ◽  
...  
Keyword(s):  
Steroid Therapy ◽  
Central Line ◽  
Blood Cultures ◽  
High Dose ◽  
Cell Transplant ◽  
Coagulase Negative Staphylococci ◽  
Hematopoietic Stem ◽  
Surveillance Cultures ◽  
Number Of Patients ◽  
Clinically Significant

Abstract Background Treatment of GvHD with steroids increases the risk of infection in HSCT patients due to additive immunosuppression and may delay the diagnosis of infection due to lack of symptoms. Outpatient surveillance blood cultures in HSCT with GvHD being treated with HD steroids has demonstrated a blood culture positivity rate of 3.5%. Currently, the utility of surveillance cultures in patients receiving LD steroid therapy is unknown. Our practice includes weekly outpatient surveillance cultures for all GvHD patients treated with steroids regardless of the dose. The primary endpoint of this study was to assess the incidence of positive surveillance blood cultures in GvHD patients receiving HD or LD steroids. Secondary endpoints included number of patients treated, hospitalization, 30 day mortality due to infection, and organisms isolated. Methods This was a single-center, retrospective review of GvHD patients at Yale New Haven Hospital between January 2013 and May 2019. Patients were excluded if: lack of signs or symptoms of GvHD, treatment with steroids for any indication other than GvHD, and active GvHD without central line. Cultures from patients receiving antibiotics for concurrent infection were also excluded. Results A total of 71 patients met criteria with 901 blood cultures. On HD, eight patients (14%) had 12 positive cultures (4%), and on LD, 16 patients (25%) had 22 positive cultures (4%) (p=0.15). Treatment occurred in six patients (75%) with four (24%) requiring hospitalization on HD, and 12 patients (75%) with 10 (83%) requiring hospitalization on LD (p=0.45). The median duration of steroid therapy was 93 and 236 days with a median dose of steroids of 1mg/kg/day and 0.15mg/kg/day, respectively. The number of positive cultures/1000 steroid days was 1.2 on HD and 0.5 on LD (RR 2.2). 30 day mortality was only noted in one patient (8%) on LD. The most common organism in both groups was Coagulase-negative staphylococci with all six cultures on HD classified as contaminants and 6/10 cultures requiring treatment on LD. Conclusion Although the relative risk of positive surveillance blood cultures in HD patients compared to LD was twofold higher, there were clinically significant infections identified in the LD group. Disclosures All Authors: No reported disclosures

Routine Surveillance for Bloodstream Infections in a Pediatric Hematopoietic Stem Cell Transplant (HSCT) Cohort: Do Patients Benefit?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5268-5268
Author(s):  
Conrad Fernandez ◽  
Heather Rigby ◽  
Joanne Langley ◽  
Timothy Mailman ◽  
Bruce Crooks ◽  
...  
Keyword(s):  
Antimicrobial Therapy ◽  
Care Center ◽  
Central Venous Access ◽  
Health Centre ◽  
Central Line ◽  
Blood Cultures ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Health Care Center ◽  
Surveillance Cultures

Abstract Background: HSCT recipients are at high risk of late bloodstream infection (BSI). Controversy exists regarding the benefit of surveillance blood cultures in this immunosuppressed population. Despite the common use of this practice, its practical value is not well established in non-neutropenic children following HSCT. Methods: At the IWK Health Centre, a tertiary health care center serving 2.5 million in the three Maritime provinces of Canada, weekly surveillance blood cultures from central venous access lines (CVLs) are drawn from children following HSCT until CVL removal. We reviewed data from a prospectively collected CVL database in association with a health record review to determine the utility and cost of this practice. Eligible participants were non-neutropenic pediatric HSCT recipients with CVLs followed at the IWK between 1999 and 2005. Patients routinely received PCP and penicillin prophylaxis. Cultures were considered to be for surveillance if the child was afebrile without focus of infection. The cost of laboratory investigations, nursing time, hospital stay, and interventions for positive surveillance cultures was calculated. Results: 43 HSCTs were performed in 41 patients of whom 21 were male (49%). The median age was 7 years (range 1–18). Donors were related in 15 cases (35%), unrelated in 18 (42%) and autologous in 10 cases (23%). The most common underlying illness leading to HSCT was leukemia (19/41; 46%) followed by solid tumour (7; 17%), inborn errors of metabolism and Fanconi Anemia (4 each; 10%) and other (4;10%). The median length of study eligibility, defined as the point at which the patient returned to the IWK from the transplant centre until the time of central line removal, was 70 days (range 7–176). There were 316 patient contacts for surveillance cultures (mean 7 per transplant) and 577 central line lumens sampled. Three patients had potentially clinically significant surveillance blood cultures that were positive (3/43; 7%). The bacteria isolated were Klebsiella pneumoniae (n=2) and Corynebacterium jeikium (n=1). Repeat cultures were done prior to initiation of antimicrobial therapy and all were sterile. Patients were admitted for antimicrobial therapy if they were not already hospitalized for HSCT care. Median hospitalization for treatment of the positive culture was 5 days. All three patients had an uncomplicated course. The estimated total cost of BSI surveillance and treatment of asymptomatic infection over 6 years was $27,989. Conclusion: This study suggests that BSI surveillance in children post engraftment has a very low yield and significant cost. It is unclear that it contributes to improved patient outcomes.

scholarly journals Routine Surveillance for Bloodstream Infections in a Pediatric Hematopoietic Stem Cell Transplant Cohort: Do Patients Benefit?

2007 ◽  
Vol 18 (4) ◽  
pp. 253-256 ◽  
Author(s):  
Heather Rigby ◽  
Conrad V Fernandez ◽  
Joanne Langley ◽  
Tim Mailman ◽  
Bruce Crooks ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Antimicrobial Therapy ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Health Centre ◽  
Blood Cultures ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Surveillance Cultures

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients are at a high risk for late bloodstream infection (BSI). Controversy exists regarding the benefit of surveillance blood cultures in this immunosuppressed population. Despite the common use of this practice, the practical value is not well established in non-neutropenic children following HSCT.METHODS: At the IWK Health Centre (Halifax, Nova Scotia), weekly surveillance blood cultures from central lines are drawn from children following HSCT until the line is removed. A retrospective chart review was performed to determine the utility and cost of this practice. Eligible participants were non-neutropenic HSCT recipients with central venous access lines. The cost of laboratory investigations, nursing time, hospital stay and interventions for positive surveillance cultures was calculated.RESULTS: Forty-three HSCTs were performed in 41 children. Donors were allogenic in 33 cases (77%) and autologous in 10 cases (23%). There were 316 patient contacts for surveillance cultures (mean seven per patient) and 577 central line lumens sampled. Three of 43 patients (7%) had clinically significant positive surveillance blood cultures. Bacteria isolated wereKlebsiella pneumoniae(n=2) andCorynebacterium jeikeium(n=1). All follow-up cultures before initiation of antimicrobial therapy were sterile. All three patients were admitted for antimicrobial therapy if they were not already hospitalized and/or had an uncomplicated course. The estimated total cost of BSI surveillance and management of asymptomatic infection over six years was $27,989.CONCLUSION: The present study suggests that BSI surveillance in children following HSCT engraftment has a very low yield and significant cost. It is unclear whether it contributes to improved patient outcomes.

scholarly journals 205. Rectal Stool Surveillance Cultures to Guide Empiric Antibiotic Therapy in Patients with Hematologic Malignancies with or without Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S106-S106
Author(s):  
Afrah S Sait ◽  
Shalom S Patole ◽  
Kathryn Dzintars ◽  
Sara E Cosgrove ◽  
Seema Mehta Steinke
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Broad Spectrum ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
Empiric Antibiotic Therapy ◽  
Lower Probability ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Surveillance Cultures

Abstract Background Patients with hematologic malignancies (HM) or hematopoietic stem cell transplant (HSCT) commonly receive broad-spectrum antimicrobials, often leading to the development of multidrug resistant organisms (MDRO). At our institution, rectal stool surveillance cultures (SSC) are done weekly on admitted adult patients with HMs or HSCT. The objective of this study is to determine the role of SSCs in predicting the development of a sterile site infection (StSI) with the same MDRO as identified in the SSC. Methods We retrospectively evaluated StSIs (blood, CSF, sputum/respiratory, pleural fluid, and urine) and SSC data from 242 adult patients admitted to the adult oncology ward at a large academic tertiary care center from 6/1/2017 to 2/28/2019. Demographics, SSC data, and StSIs in a 3-month period following the last SSC for each patient were collected from electronic medical records. SSCs were cultured on HardyCHROM ESBL™ media. MDRO similarity between SSC and StSI was determined by comparing susceptibility profiles. JMPÒ Pro 14.3.0 and RStudio were used for statistical analyses. Results Two hundred forty-two patients yielded 732 SSCs. We eliminated SSCs with incomplete (&lt; 3 months of follow up) data. Thus, 579 SSCs were included in the analyses. 64% of patients were male. Leukemias (55.4%), lymphomas (21.9%), and multiple myeloma (10.3%) were the most common HMs. HSCT recipients comprised 50.4%. SSCs were positive for a MDRO in 251 cases (vancomycin-resistant enterococci, 52.2%; extended-spectrum beta-lactamase (ESBL) producing organisms, 22.2%; and carbapenamase producing organisms, 4.4%). There were 54 StSIs documented where the MDRO was the same as the SSC MDRO. The NPV of the SSC was 95.1% (95%CI 0.93,0.97). The positive likelihood ratio of the SSC was 2.5 (95%CI 2.07,3.02). Conclusion Our results suggest that a negative SSC is associated with a lower probability of identifying a StSI with an MDRO. Clinically, this can be useful in providing the opportunity to judiciously guide antimicrobial therapy, thereby avoiding the unnecessary usage of broad-spectrum antimicrobials when no MDRO is identified in the SSC. Disclosures All Authors: No reported disclosures

Mitigating the risk of transfusion-transmitted bacterial infections in hematology oncology patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19047-e19047
Author(s):  
Harold Alvarez ◽  
Marion Lanteri ◽  
Guenther Koehne
Keyword(s):  
Bacterial Infections ◽  
Bacterial Culture ◽  
Emerging Infectious Diseases ◽  
Bloodstream Infections ◽  
Central Line ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Life Saving ◽  
The Uk ◽  
Transfusion Reactions

e19047 Background: Hospital acquired infections create major logistical, financial, and patient safety concerns within the healthcare system. Bacterial contamination (BC) of platelet components (PCs) can lead to transfusion-transmitted bacterial infections (TTBI), central line-associated bloodstream infections, and sepsis, with long-term complications and/or death. In the US, hematopoietic stem cell transplant (HSCT) recipients require transfusion support until engraftment and together with hematology/oncology (hemonc.) patients receive the highest number of PCs/patient. FDA’s Guidance recommends approaches to reduce BC risk including the use of enhanced bacterial culture screening (EBSC) or pathogen reduction (PR) of platelets. Methods: The Miami Cancer Institute (MCI) implemented PR-PCs for all allogeneic HSCT patients. Irradiation, CMV testing, and bacterial screening have been discontinued for PR-PCs. Transfusion outcomes are being monitored using active hemovigilance (HV) reporting. Results: Considering the fatality risk associated with BC of PCs (1:200,000 – 1:1,000,000) despite the use of optimal skin cleansing, initial sample diversion, and primary bacterial culture, 1/2,880 PCs are still contaminated (Bloch et al.); further steps towards BC mitigation are needed. As the UK and US reported a residual BC risk of 5.4-9.4/million PCs after implementation of EBSC, PR may represent an alternative approach with other cumulative benefits. Indeed, national HV data from France, Switzerland and Belgium reported no sepsis transfusion reactions since PR implementation (Benjamin et al.). In addition, the risk of TA-GVHD and other TTI including emerging infectious diseases (EID) may be decreased after the inactivation of pathogens and leukocytes (Lanteri et al.). At MCI, the percentage of transfused PR-PCs has been increasing steadily from 7.9% in July 2019 to 22.2% in January 2021. Over a 19 month-period, a total of 9,296 PC were transfused including 1,677 PR-PCs. While non-PR-PCs were all irradiated and bacterially screened, PR-PC were neither irradiated nor bacterially screened. No cases of TA-GVHD or TTI were reported. A total of 27 mild, non-life-threatening platelet transfusion reactions were reported including 22 (81.5%) after non-PR PCs transfusion and 5 (18.5%) after PR-PC transfusion. In addition, the early release of transfusion-ready fresh PR-PCs 24-48 hours after collection has proven invaluable in providing clinicians and patients with blood continuity during the COVID-19 pandemic. Conclusions: Though certain measures have improved blood safety, the risk of TTI associated with PC transfusion remains a concern for vulnerable hemonc. patients. Using PR-PC is especially important to consider when patients undergo extensive life-saving therapies such as bone marrow transplants.

scholarly journals 1098. Norovirus Infection in Cancer Patients Undergoing Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S578-S579
Author(s):  
Divya S Kondapi ◽  
Sasirekha Ramani ◽  
Adilene Olvera ◽  
Robert L Atmar ◽  
Mary K Estes ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Nucleic Acid Amplification ◽  
High Dose ◽  
Cell Transplant ◽  
Research Support ◽  
Hematopoietic Stem ◽  
Car T Cell ◽  
Car T

Abstract Background CAR-T is used to treat certain refractory hematological malignancies. B-cell aplasia and immunosuppression used to treat CAR-T side effects increase infection risk. Little data are available describing Norovirus (NoV) infections in CAR-T recipients. Methods We reviewed the medical records of 134 patients with NoV diarrhea (identified by nucleic acid amplification test) between 2016-2019. Of these patients, nine received CAR-T prior to developing NoV. Here we describe their demographics, clinical characteristics, treatments, and complications. Results The median age was 49 years (Table 1). Patients’ underlying malignancies included Non-Hodgkin’s Lymphoma (4), Acute Lymphoblastic Leukemia (3), Chronic Lymphocytic Leukemia (1) and metastatic Sarcoma (1). Prior to development of NoV, six patients had undergone hematopoietic stem cell transplant, and 1 had received checkpoint inhibitor therapy. Five patients experienced cytokine release syndrome after CAR-T, and 1 experienced CAR-T-related encephalopathy syndrome (Table 2). Two patients received interleukin-6 antagonist therapy, and one received high dose steroids. Time to diarrhea onset post-CAR-T cell infusion was variable(median 256days, IQR 26-523 days).Six had an absolute lymphocyte count&lt; 1000/mm3 at diarrhea onset. Three had diarrhea for &gt;14 days; median diarrhea duration in the other 6 patients was 4 days. Other GI complaints included abdominal pain (3), nausea (4), and vomiting (3). For NoV treatment, three received oral immunoglobulin, and 8 received Nitazoxanide. Complications included development of concomitant GI-GVHD(5), ileus (2), need for TPN (3), renal failure requiring dialysis (2), ICU stay (3), and death (2). Two patients were co-infected with other enteropathogens such as rotavirus, enteropathogenic and enteroaggregative E.Coli and Clostridioides difficile. Three patients with diarrhea lasting &gt;14 days had serial samples collected over time; NoV shedding lasted 81-546 days. NoV was genotyped in 6 patients(Table 3) and included GII.2(2), GII.4(2), GII.6(1) and GII.12(1). Table 1: Patient characteristics (N=9) Table 2: CAR-T related factors Table 3: NoV Genotypes Conclusion NoV belonging to various genotypes is an important cause of acute and chronic diarrhea in patients receiving CAR-T cell therapy. Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary K. Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support)

scholarly journals Expanding the Indications for Ibrutinib: Complete Remission Obtained By Induction with Ibrutinib Followed By Consolidative Ahsct in Refractory Primary CNS Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5631-5631 ◽  
Author(s):  
Cassidy Brothers
Keyword(s):  
Complete Remission ◽  
Disease Progression ◽  
Salvage Therapy ◽  
B Cell Lymphoma ◽  
Salvage Treatment ◽  
Severe Neutropenia ◽  
High Dose ◽  
Cell Transplant ◽  
Curative Intent ◽  
Hematopoietic Stem

Introduction Primary central nervous system lymphoma (PCNSL) is an exceedingly rare and aggressive sub-type of Non-Hodgkin's Lymphoma. Despite initial polychemotherapy that includes High-Dose Methotrexate (HD-MTX), over half of patients will develop recurrent or refractory disease that requires salvage therapy.1 Ibrutinib, a Bruton's tyrosine kinase inhibitor, has become an alternative for salvage treatment in relapsed or refractory PCNSL (RR-PCNSL) that is particularly useful in patients who are ineligible for re-induction with HD-chemo. In RR-PCNSL, Ibrutinib led to a progression free survival (PFS) of roughly 5 months when used as monotherapy2,3 and 15 months when used as add-on therapy.4 While its role as salvage treatment has been documented, its use to facilitate consolidative autologous hematopoietic stem cell transplant (AHSCT) in RR-PCNSL is not currently known. The following case describes the first known report of a patient with RR-PCNSL who achieved persistent complete remission following Ibrutinib salvage treatment and consolidative AHSCT. Case Description A 64-year-old male presented to the emergency department with a two-week history ptosis, visual abnormalities, confusion, and increasing fatigue. On physical exam, he was found to have bilateral mydriasis, left third nerve cranial palsy, severe left-sided ptosis, and restricted upwards and downward gaze of the right eye. A contrast-CT was performed which showed multiple areas of abnormal enhancement throughout the frontal lobes, corpus callosum, and midbrain associated with significant vasogenic edema. These findings were confirmed on MRI. He underwent a stereotactic guided burr hole biopsy which was consistent with diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry performed on the tissue showed that the neoplastic cells were CD3(-), CD5(-), CD20(+), CD10(-), BCL2(subset +), BCL6(+), MUM1(+) and Cyclin D1(-). Staging CT and bone marrow biopsy showed no evidence of systemic disease. He was diagnosed with PCNSL and went on to receive induction therapy with Rituximab, Methotrexate, Procarbazine, and Vincristine (R-MPV) with curative intent and received a total of 7 cycles. Initially, he had a significant radiographic response with a repeat MRI post cycle 4 showing only a few small areas of residual enhancement. However, after completion of the 7 cycles of R-MPV, his MRI showed evidence of disease progression with both new and enlarging intra-axial lesions. Given his ECOG of 0 and lack of comorbidities, it was decided that he would proceed with salvage treatment with Cytarabine and Etoposide with curative intent for refractory PCNSL. Unfortunately, after only four weeks of receiving cycle one of Cytarabine and Etoposide, a repeat MRI showed evidence of disease progression. He was then transitioned to palliative therapy with prednisone up until December 2017, at which point he was able to obtain Ibrutinib on a compassionate basis. He was started on Ibrutinib salvage therapy and achieved radiographic evidence of complete remission after four months of treatment. There were minimal adverse effects of Ibrutinib therapy, most notably a severe neutropenia requiring a temporary discontinuation of therapy for two weeks. He underwent consolidative AHSCT with Thiotepa, Busulfan and Melphalan conditioning in August 2018. His post-transplant course was complicated by culture negative febrile neutropenia with a subsequent source determined to be Clostridium difficile for which he was treated. An MRI head performed 3 months after his AHSCT showed no evidence of recurrent or residual disease. He continues to be followed by the Hematology Service in Newfoundland and has remained in complete remission since. Conclusions This case demonstrates the feasibility of a salvage approach using Ibrutinib followed by AHSCT when standard salvage options have been exhausted in refractory PCNSL. OffLabel Disclosure: Ibrutinib's indications do not currently include use as a induction treatment prior to AHSCT in refractory/recurrent PCNSL.

scholarly journals Immunosuppressive Compounds Affect the Fungal Growth and Viability of Defined Aspergillus Species

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 273 ◽  
Author(s):  
Stanislaw Schmidt ◽  
Michael Hogardt ◽  
Asuman Demir ◽  
Frauke Röger ◽  
Thomas Lehrnbecher
Keyword(s):  
Fungal Growth ◽  
Invasive Fungal Disease ◽  
Inhibitory Effect ◽  
Immunosuppressive Drugs ◽  
Aspergillus Species ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Species Specific ◽  
The Impact

Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.

Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3228-3228
Author(s):  
Elizabeth Berger ◽  
Christopher Seet ◽  
Mala Parthasarathy ◽  
Tulio Rodriguez ◽  
Scott E. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Cell Mobilization

Abstract Abstract 3228 Poster Board III-165 Introduction Using standard dose G-CSF (10 μg/kg) for stem cell mobilization, 25-40% of patients, deemed to be hard to mobilize based on prior therapy, will not collect sufficient HSC (> 2-2.5 × 106 CD34/kg) to proceed to a prompt autotransplant. Strategies to improve CD34/kg yields have included dose escalating G-CSF up to 30 μg/kg or combining G-CSF and GM-CSF. While dose escalated G-CSF is effective in increasing CD34 yields in normal donors as is the combination of G-CSF and GM-CSF, their comparative value in pre-treated patients has not been tested. To determine the value of these strategies, we performed a randomized comparison of high dose G-CSF (30 μg/kg as 2 doses 12 hours apart), to the combination of simultaneous single daily doses of G-CSF (10 μg/kg) plus GM-CSF (5 μg/kg), to a control group receiving G-CSF at an equivalent total dose of cytokine to the combination arm (15μg/kg) as a single dose. Patients and Methods Patients were eligible if heavily pre-treated, defined as: a minimum of 10 total cycles of combination chemotherapy and two prior regimens, or a total of 6 chemotherapy cycles if the patient also received RT to marrow bearing sites, platinum-based chemotherapy or 2 or more cycles of any BCNU or fludarabine containing regimen. Baseline WBC had to be > 3000/μl, ANC > 1500/μl and a platelets > 100,000/μl. Twelve liter aphereses began on day 5 of mobilization, and continued until ≥ 4 × 106 CD34/kg were collected or a maximum of 5 aphereses. Patients typically proceeded to transplant if they had ≥ 2.5 × 106 CD34/kg collected and were always re-mobilized if they collected < 2.0 × 106 CD34/kg. CD34 subsets (CD34+/CD33- and CD34+/CD38-) were also assessed for the 3 groups to determine if more primitive HSC were mobilized by the 2 novel strategies. The sample size was calculated based as follows: 60% of the control group would collect 2.5 × 106 CD34/kg and this would rise to 90% in one or both study arms. The detection of such differences with a power of 80% and a 2-sided alpha level of 0.025 required a total sample of 120 patients. Results A total of 120 patients were randomized; 119 were eligible. Patient demographics, shown in the Table, were matched among the three groups: The % of patients collecting ≥2.5 × 106 CD34/kg was: standard G: 60%, high dose G: 57% (p = 1.0), G + GM: 41% (p = 0.1). Median CD34 collected in first mobilization were, 3.6 × 106/kg, 3.0 × 106/kg (p = 0.22) and 2.0 × 106/kg (p = 0.05) respectively in a median of 4, 4, and 5 aphereses (p = NS). Re-mobilization rates: standard G; 37.5%, high dose G: 35%; G + GM: 50% (p = NS). Total median CD34 collected from first and any second mobilizations were: standard G: 4.8 × 106/kg, high dose G: 3.9 × 106/kg, and G + GM: 3.5 × 106/kg. One patient in the standard G arm and 3 in high dose G did not proceed to transplant due to poor initial mobilization and progression in 2, and one each for progression or poor mobilization alone. There were no significant differences in median engraftment times: for ANC, 10, 11 and 15 days respectively for the standard G-, high dose G- and G + GM arms and for platelets, 11, 13 and 14 days respectively. The overall survivals @ the median f/u time of 37 months were 59.8%, 61.8% and 48.1% respectively (p = 0.272) for the three groups. The % primitive HSC (CD34+/CD33- and CD34+/CD38-) from the first mobilization were identical in the 3 patient groups. Conclusions We found no advantage to dose escalated G-CSF nor to the combination of G-CSF and GM-CSF to mobilize HSC for autotransplantation in heavily pre-treated patients. We also did not find higher numbers of more primitive CD34 subsets mobilized by these newer strategies. Alternative approaches, e.g. the combination of plerixifor + standard dose G-CSF (Stiff et al: BBMT; 15:249-56, 2009) would appear to be the preferred method of initial HSC mobilization for heavily pre-treated patients. Disclosures Stiff: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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