Hematopoietic Cell Mobilization for Gene Therapy of Adult Patients with Severe Beta-Thalassemia: The Challenge of Splenectomy and the Role of Plerixafor

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 166-166
Author(s):  
Evangelia Yannaki ◽  
Thalia Papayannopoulou ◽  
Erica Jonlin ◽  
Fani Zervou ◽  
Garyfalia Karponi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Statistical Significance ◽  
Adult Patients ◽  
Beta Thalassemia ◽  
Off Label ◽  
Gene Therapy Trial ◽  
Cd34 Cells ◽  
Significant Difference ◽  
The Mean ◽  
Cell Mobilization

Abstract Abstract 166FN2 In preparation for a trial for gene therapy of thalassemia, we investigated the safety and efficacy of stem cell mobilization in adult patients with severe thalassemia using either GCSF or Plerixafor. We first assessed mobilization with G-CSF or G-CSF following pretreatment with Hydroxyurea (HU). HU was used in non splenectomized patients in order to reduce extramedullary hemopoiesis in spleen and the splenic size and in splenectomized patients in order to decrease the high number of platelets and mainly WBCs before G-CSF, so as to reduce the chance of complicated leukocytosis during mobilization. We present data on 23 patients from the G-CSF study (EudraCT number 2005-000315-10, NCT00336362) and on 14 patients from the Plerixafor study (EudraCT number 2009–014136-37, NCT01206075). The bulk of the CD34+cell enriched leukaphereses product in either study was cryopreserved for the future gene therapy trial. Mobilization with G-CSF was safe and effective in non-splenectomized patients (CD34+cellsX106/kg/2aphereses: 6.67±2.87, n=6). HU+G-CSF-treated subjects (n=4), mobilized successfully only when an optimal wash out period of approximately two weeks was maintained before G-CSF administration (CD34+cellsX106/kg/2aphereses: 7.34±1.19 vs 1.86±0.76, respectively, p=0.03). HU reduced the spleen size before G-CSF (376±96cm3 vs 556±218cm3) and resulted in less splenic enlargement during mobilization as compared to non-HU pretreated subjects (26.8% vs 60%, p=0.1), although this difference did not reach statistical significance. Splenectomized patients responded excessively to G-CSF by developing early hyperleukocytosis (day 3 mean WBCs: 80.0±7.5×103/μl) without a corresponding rise in blood CD34+cells. This necessitated a significant G-CSF dose reduction or hold resulting in poor yields in the majority of cases (CD34+cells/kg/2aphereses: 2.0±1.7, n=4). One-month HU-pretreatment (n=9), prevented the G-CSF-associated hyperleukocytosis during mobilization (mean WBCs: 60.4±20.8×103/μl) allowing for safe and successful CD34+cell collections (CD34+cells/kg/2aphereses: 6.6±2.3, p=0.02 vs G-CSF-alone), but again, only when an optimal 2-week wash out period was maintained. Despite the safe and effective mobilization with the optimal HU+G-CSF combination of splenectomized patients, HU pretreatment significantly prolonged the mobilization procedure. Plerixafor induced a rapid and effective mobilization in both the splenectomized and non-splenectomized patients (CD34+celsX106/kg/1 or 2 aphereses: 7.29±1.82, n=8 and 5.38±1.99, n=6, respectively) and it was very well tolerated. In SPL subjects, the mean yield per apheresis with plerixafor was higher, with a trend to significance, over its G-CSF counterpart and similar to the mean yield obtained by the optimally HU+G-CSF-treated patients in the G-CSF study (CD34+cells/kgX106/apheresis: 4.19±3.13 vs 1.01±0.85 vs 3.32±1.16, p=0.06 and p=0.6 respectively). One patient who was remobilized with the combination of G-CSF+plerixafor due to previous failure to collect 32×106/kg/2aphereses with G-CSF-alone, yielded 6.5χ10^6 CD34+cells/kg by one apheresis. Importantly also for the non-SPL patients treated with plerixafor, a mean increase of splenic volume of 10.9±14.3% was encountered which was significantly lower than the 60% mean spleen volume increase during G-CSF mobilization (p=0.03). There was no significant difference in the clonogenic capacity (CFU-GM, BFU-E) of CD34+cells mobilized by G-CSF, HU+G-CSF or Plerixafor. However, there was a trend for Plerixafor to mobilize more primitive HSC subpopulations (CD34+/CD38−, CD34+/CD38−/HLADR−) as compared to HU+G-CSF- or G-CSF-alone-mobilized cells. These results suggest that either G-CSF or Plerixafor could be used for mobilizing non-splenectomized patients. Plerixafor seems to represent the agent of choice for mobilization of splenectomized patients with thalassemia. Disclosures: Off Label Use: Plerixafor is used off-label for mobilization of thalassemic subjects.

Limitations of G-CSF Mobilization in Splenectomized Patients with Beta-Thalassemia Major: Implications for Thalassemia Gene Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2150-2150
Author(s):  
Evangelia Yannaki ◽  
Thalia Papayannopoulou ◽  
Erica Jonlin ◽  
Ioannis Batsis ◽  
Pamela S. Becker ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Splenic Rupture ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Adult Patients ◽  
Cell Yield ◽  
Beta Thalassemia ◽  
Limited Information ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract Abstract 2150 Poster Board II-127 For gene therapy (GT) of thalassemia (TH), high numbers of genetically-modified hematopoietic stem cells (HSCs) are required to effectively compete for niche space in the hypercellular thalassemic bone marrow (bm). Mobilized peripheral blood is the preferable source of HSCs for thalassemia GT due to higher yields of CD34+cells compared to bm harvest. There is limited information on the mobilization efficacy of adult patients with major β-TH as well as on the safety of the procedure in a condition of splenomegaly and extramedullary hemopoiesis. Rare events of splenic rupture or thrombosis with G-CSF in normal donors raise safety concerns for its use in TH where chronic splenomegaly and hypercoagulability exist. Pretreatment of patients with hydroxyurea (HU) could reduce the risk of splenic rupture or thrombosis by decreasing the splenic hemopoiesis and thereby the spleen size in the non-splenectomized (non-SPL), and the circulating cells in the splenectomized (SPL) patients before G-CSF. In an on going mobilization study, we aim to assess the safety and efficacy of G-CSF mobilization with or without HU pretreatment in adult patients with β-TH major. Sufficient mobilization is considered to be the yield of ≥2×106CD34+cells/kg/2aphereses. Sixteen patients have been enrolled so far, 9 SPL and 7 non-SPL. One non-SPL patient withdrew during the study. Six SPL and 4 non-SPL patients received HU pretreatment (20mg/kg/d the non-SPL, 25-30mg/kg/d the SPL) for 1 month before G-CSF. There was a 1-2 weeks' interval between HU cessation and G-CSF initiation. No severe adverse events were observed. In non-SPL patients, HU decreased the spleen volume over baseline (306cm3 vs 536cm3, p=0,03) resulting in 9% max increase during mobilization compared to 45% size increase in patients w/o HU pretreatment. In non-SPL patients, HU negatively affected the CD34+yield when the ‘wash-out' period before G-CSF was 8 days (mean CD34+cells 1,86±0,76×106/kg/2aphereses, n=2). However, when the interval period from the HU stop to the G-CSF initiation increased up to 18 days allowing for bm recovery after the myelosuppressive effect of HU, mobilization was successful (P12:CD34+cells 6,5×106/kg/2aph). Non-SPL patients w/o HU pretreatment (n=3) yielded adequate numbers of HSCs (CD34+cells:5,8±3,89×106/kg/2aph). Surprisingly, CD34+cell yields were very low in the first 2 non-HU pretreated SPL patients (CD34+cells:0,98±0,14×106/kg/2aph). This was due to the development of early excessive leukocytosis (mean max WBCs 81×109/l, day 3) with the regular 10mcg/kg/d G-CSF dose, which necessitated dose hold or therapeutic leukapheresis and resulted in loss of the CD34+cell peak in blood. However, when mobilization started with lower (2,5mcg/kg/d) and adjusted to the WBCs doses of G-CSF (mean daily dose 3,21mcg/kg) and aphereses were initiated later (day6), CD34+cell yield markedly improved (P15:4,5×106/kg/2aph) without inducing early excessive leukocytosis (max WBCs 67×109/l, day 5). In SPL patients, HU was shown to decrease the high PLT and WBC numbers before G-CSF (PLTs:from 640±132×109/l at baseline to 240±53×109/l, p=0,0002 / WBCs:from 20,23±15,8×109/l at baseline to 11,47±6,11×109/l, p=0,23) potentially reducing the risk of thrombosis and partially preventing excessive leukocytosis during mobilization (max WBCs SPL-HU:51,68±29,37×109/l vs SPL-no HU:74,77±8,78×109/l, p=0,23). HU pretreatment negatively affected the yield in SPL patients when the ‘wash-out' period before G-CSF was 7-10 days (mean CD34+yield 0.62±0,41×106/kg/2aph, n=5). However, when the interval period from HU stop to G-CSF initiation increased up to 12 days, mobilization was successful (P16:CD34+cells 3,8×106/kg/2aphereses). G-CSF dose adjustment was also needed in HU-pretreated SPL patients with WBCs≥14,6×109/l before G-CSF (P9,P16). Overall, it seems that mobilization of SPL thalassemic patients is challenging. Mobilization is not inherently inefficient in SPL patients but it results from mandatory G-CSF-dose modifications to avoid hyperleukocytosis. Patient-tailored schemes of G-CSF mobilization or alternative ways of mobilization (ie AMD 3100) will be required in order to obtain high numbers of HSCs from SPL patients. HU seems to play a safety role as pretreatment before mobilization, especially in the SPL patients, however the time to G-CSF initiation after HU cessation is critical for a sufficient CD34+cell yield. Disclosures: No relevant conflicts of interest to declare.

scholarly journals HEMATOLOGICAL CHARACTERIZATION OF BETA-THALASSEMIA IN SUDANESE PATIENTS

2020 ◽  
pp. 5-7
Author(s):  
RABAB HASSAN ELSHAIKH ◽  
SANAA ELFATIH HUSSEIN
Keyword(s):  
Iron Deficiency ◽  
Hemoglobin Concentration ◽  
Mean Value ◽  
Beta Thalassemia ◽  
Mean Corpuscular Hemoglobin ◽  
Corpuscular Hemoglobin ◽  
Significant Difference ◽  
Hematological Analysis ◽  
The Mean

Thalassemia is common inherited disorder among humans, and they represent a major public health problem in many areas of the world. The study aimed to the measurement of hematological characterization of beta-thalassemia in Sudanese patients. Blood samples from 61 beta-thalassemic patients were collected after written consent form obtained from all participants. The frequency of adults (>18 years) was 45 (73.8%) and children’s (<18 years) was 16 (26.2%); the frequency of male was 27 (44.3%) and 34 were female (55.7%). Hemoglobin estimation and red cell indices were carried out using the automatic blood cell counter Sysmex K × 21N. The results showed that Hb and RBCs indices were varied between mild to moderate and severe decreasing, hemoglobin concentration (Hb) with the mean value of 9.6 g/dL, with minimum value of 6.1 g/dl and maximum of 11.9 g/dl, while RBCs were increased in all patients, mean value 5.2 c/l, mean corpuscular volume mean was 58.9 fl, hematocrit was 30.4, mean corpuscular hemoglobin (MCH) 18.8 pg, mean corpuscular hemoglobin concentration (MCHC) was 31.7pg, and RDW was 18.8%. The method used for hemoglobin electrophoresis was capillary electrophoresis, Hb pattern shows increased HbA2 and HbF, the mean of HbA is 78.3%, HbF is 2.3%, and HbA2 is 6.5% with the min. value of 3.6% and max. of 12.2%. While the mean of serum iron was 82.75 μg/dl, 7 patients showed low level, 19 high level, and 35 were normal level. Comparison of hematological analysis (HbA2) in thalassemic patients coexisted with iron deficiency and without result was insignificant difference (p=0.645), this result disagrees with references that say iron deficiency masking HbA2. Nevertheless, the association between HbA2 and HbF revealed a statistically significant difference (p<0.013) and HbA2 with Hb was insignificant (p=0.260).

Effects of Orthokeratology Lens On Axial Length Elongation in Myopia With Anisometropia Children

2021 ◽  
Author(s):  
Ziyang Chen ◽  
Kai-Ming Chen ◽  
Ying Shi ◽  
Zhao-Da Ye ◽  
Sheng Chen ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Axial Length ◽  
Statistical Significance ◽  
Spherical Equivalent ◽  
Significant Difference ◽  
The Mean ◽  
The Difference ◽  
Better Than ◽  
Group 1

Abstract AimTo investigate the effect of orthokeratology (OK) lens on axial length (AL) elongation in myopia with anisometropia children.MethodsThirty-seven unilateral myopia (group 1) and fifty-nine bilateral myopia with anisometropia children were involved in this 1-year retrospective study. And bilateral myopia with anisometropia children were divided into group 2A (diopter of the lower SER eye under − 2.00D) and group 2B(diopter of the lower SER eye is equal or greater than − 2.00D). The change in AL were observed.The datas were analysed using SPSS 21.0.Results(1) In group 1, the mean baseline AL of the H eyes and L eye were 24.70 ± 0.89 mm and 23.55 ± 0.69 mm, respectively. In group 2A, the mean baseline AL of the H eyes and L eyes were 24.61 ± 0.84 mm and 24.00 ± 0.70 mm respectively. In group 2B, the mean baseline AL of the H eyes and L eyes were 25.28 ± 0.72 mm and 24.70 ± 0.74 mm. After 1 year, the change in AL of the L eyes was faster than the H eyes in group 1 and group 2A (all P<0.001).While the AL of the H eyes and L eyes had the same increased rate in group 2B. (2) The effect of controlling AL elongation of H eyes is consistent in three groups (P = 0.559).The effect of controlling AL elongation of L eyes in group 2B was better than that in group 1 and group 2A (P < 0.001). And the difference between group 1 and group 2A has no statistical significance. (3) The AL difference in H eyes and L eyes decreased from baseline 1.16 ± 0.55mm to 0.88 ± 0.68mm after 1 year in group 1.And in group 2A, the AL difference in H eyes and L eyes decreased from baseline 0.61 ± 0.34mm to 0.48 ± 0.28mm. There was statistically significant difference (all P<0.001). In group 2B, the baseline AL difference in H eyes and L eyes has no significant difference from that after 1 year (P = 0.069).ConclusionsMonocular OK lens is effective on suppression AL growth of the myopic eyes and reduce anisometropia value in unilateral myopic children. Binocular OK lenses only reduce anisometropia with the diopter of the low eye under − 2.00D. Binocular OK lenses cannot reduce anisometropia with the diopter of the low eye equal or greater than − 2.00D. Whether OK lens can reduce refractive anisometropia value is related to the spherical equivalent refractive of low refractive eye in bilateral myopia with anisometropia children after 1-year follow-up.

Factors Affecting the Clinical Outcomes of Surgically Treated Ankle Fractures Associated with the Posterior Malleolar Fragment

2021 ◽  
Vol 111 (5) ◽  
Author(s):  
Mehmet Kuyumcu ◽  
Emre Bilgin ◽  
Hasan Bombacı
Keyword(s):  
Clinical Outcomes ◽  
Fragment Size ◽  
Statistical Significance ◽  
Ankle Fractures ◽  
Foot And Ankle ◽  
Ankle Osteoarthritis ◽  
Posterior Malleolus ◽  
Significant Difference ◽  
Functional Scores ◽  
The Mean

Background This study was performed to determine the factors that influence the clinical outcomes of surgically treated ankle fractures associated with the posterior malleolus (PM). Methods We evaluated 42 fractures of 42 patients. Posterior malleolus fracture size was calculated using computed tomography. Posterior malleolar fractures with a size less than 10% were left nonfixated. The decision for larger fragments was performed using fluoroscopy following the fixation of other components. If the joint was found to be congruent, the PM was left nonfixated. Otherwise, the PM was reduced and fixated. Clinical outcomes were evaluated based on Weber, Freiburg, and American Orthopaedic Foot and Ankle Society scores. Ankle osteoarthritis was determined according to the Canadian Orthopaedic Foot and Ankle Society classification. The effect of PM fixation, age, PM fragment size, waiting period before surgery, presence of ankle dislocation, and number of injured malleoli on clinical outcomes were assessed. Statistical significance was set at a value of P &lt; .05. Results The mean patients age was 48.5 ± 14.9 years (range, 20–84 years) and the mean follow-up was 23.7 ± 8.6 months (range, 12–56 months). Fixation of the PM was performed solely in 12 patients. Postoperative displacement of the PM and articular step were less than 2 mm in all fractures. Statistically significant worse outcomes were demonstrated based on functional scores in the patients with a PM size greater than or equal to 25% (P = .042, P = .038, and P = .048, respectively) and in patients aged 60 years or older (P = .005, P = .007, and P = .018, respectively). However, there was no significant difference between functional scores and the other factors. Ankle osteoarthritis was observed at a higher rate in patients with PM size greater than or equal to 25% and in patients aged 60 years or older. Conclusions Clinical outcomes of the patients are mainly influenced by the patient's age and PM fragment size. However, if the tibiotalar joint is congruent, comparable results can be obtained in PM fixated or nonfixated patients.

Abstract 3091: Image Sharing Prior To Transfer Of Patients With Stroke

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Minal Jain ◽  
Anunaya Jain ◽  
Abhijit R Kanthala ◽  
Kate C Young ◽  
Babak S Jahromi
Keyword(s):  
Intensive Care ◽  
Sinus Thrombosis ◽  
Statistical Significance ◽  
Tertiary Care ◽  
Admission Diagnosis ◽  
Stroke Severity ◽  
Image Sharing ◽  
Interhospital Transfer ◽  
Significant Difference ◽  
The Mean

Introduction: The lack of 24X7 availability of sub-specialty neurologists and neurosurgeons in regional county hospitals frequently leads to transfer of patients with stroke/ICH to higher tertiary care centers. Transfer of patients without prior communication may delay both diagnosis as well as time sensitive treatments. Recently our institution adopted image sharing prior to transfer to facilitate triage of inter-hospital transfers. Aim: To analyze if image sharing enabled judicious selection of patients more likely to require intensive care/intervention. Methods: We analyzed consecutive adult patients with an admission diagnosis of stroke/TIA/carotid stenosis/carotid-dissection/aneursym/hemiplegia/cerebral venous sinus thrombosis for whom an interhospital transfer request was made. Results: The cohort had 197 subjects with 52.6% females. The mean age of subjects was 61.1 years (SD 16.1 years). The mean distance of healthcare facilities requesting transfer from our center was 47.7 miles (SD 28.5 miles). Of all transfer requests, 78.7% (155) were accepted to our facility, 14.7% (29) were asked to follow up in outpatient clinics, 3% (6) transfers were cancelled because a higher level of care was deemed unnecessary, 1% (2) patients declined transfer and 2.5% (5) were lost to other facilities. The median stroke severity measured by NIHSS on arrival was 3 (IQR 1 to 8). Images were shared prior to decision making for transfer for 20.3% (40) patients. Fewer patients were accepted for transfer with image sharing (73%) than without (83.7%), although this did not reach statistical significance (z statistic -1.51; p=0.132). There was no significant difference in NIHSS (p=0.3919), neurological status measured by GCS (p=0.294) or age (p=0.9942) between subjects who had image sharing versus those who did not. Amongst all accepted patients 45.1% were deemed to need intensive care and 47.7% received interventions (surgical, medical or advanced diagnostic testing). The proportion of patients who underwent intervention or were admitted to an intensive care unit was much higher when patients’ images were shared prior to transfer (85.2%) when compared to patients transferred without image sharing (56.8%; z statistic 2.755; p=0.006). The odds of undergoing intervention when patients were transferred after image sharing was 4.37 as compared to patients transferred without image sharing (95% CI 1.43 to 13.39). Conclusion: Subjects who had their images shared prior to transfer had significantly higher intervention rate. Thus image sharing is a possible tool to increase specificity for selecting patients with stroke related diagnoses, who would benefit from transfer to a tertiary care center.

scholarly journals Sexual Dimorphism in Laryngeal Volumetric Measurements Using Magnetic Resonance Imaging

2019 ◽  
Vol 99 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Abdul-Latif Hamdan ◽  
Elie Khalifee ◽  
Georges Ziade ◽  
Sahar Semaan
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Statistical Significance ◽  
Resonance Imaging ◽  
Men And Women ◽  
Mean Width ◽  
Significant Difference ◽  
The Mean ◽  
The Right ◽  
Volumetric Measurements

The objective of this study is to investigate the dimensional and volumetric measurements in the thyroarytenoid (TA) muscle in men and women using magnetic resonance imaging (MRI). The hypothesis is that there is a gender-related difference in these measurements. A retrospective chart review of 76 patients who underwent MRI of the neck at the American University of Beirut Medical Center was conducted. The dimension and volume of the right and left TA muscle were measured on axial and coronal planes short tau inversion recovery images. Male and female groups were compared with respect to demographic data and MRI findings using parametric and nonparametric tests. The mean length of the thyro-arytenoid muscle in males was larger than that in females on the right (males 2.44 [0.29] cm vs females 1.70 [0.22] cm) and on the left (males 2.50 [0.28] cm vs females 1.72 [0.24] cm) reaching statistical significance ( P < .001). The mean width of the thyro-arytenoid muscle in males was larger than that in females on the right (males 0.68 [0.13] cm vs females 0.59 [0.11] cm) and on the left (males 0.68 [0.12] cm vs females 0.57 [0.12] cm) reaching statistical significance ( P < .001). The mean height of the thyro-arytenoid muscle in males was larger than that in females on the right (males 1.05 [0.21] cm vs females 0.95 [0.12] cm) and on the left (males 1.05 [0.21] cm vs females 0.95 [0.12] cm) reaching statistical significance ( P < .01 on the right and P < .05 on the left). The volume of the thyroarytenoid muscle in males was larger than that in females on the right (males 0.86 [0.25] mL vs females 0.48 [0.15] mL) and on the left (males 0.89 [0.27] mL vs females 0.48 [0.17] mL) reaching statistical significance ( P < .001). The results of this investigation clearly indicate a significant difference in these measurements between men and women.

A Randomised Controlled Trail of Plasma Exchange in Rapidly Progressive Renal Failure of Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4899-4899
Author(s):  
William F. Clark ◽  
A. Keith Stewart ◽  
Gail A. Rock ◽  
Marion Sternbach ◽  
David M. Sutton ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Sample Size ◽  
Plasma Exchange ◽  
Kidney Failure ◽  
Statistical Significance ◽  
Control Group ◽  
Significant Difference ◽  
The Mean ◽  
Baseline Characteristics

Abstract In myeloma, plasma exchange (PE) has been suggested to prevent rapidly progressive kidney failure by reducing exposure to nephrotoxic light chains. We carried out a randomized controlled multi-centre trial comparing PE or no PE in 104 patients of whom 101 met the inclusion, exclusion criteria and 4 were lost to follow-up. We compared baseline characteristics as well as renal outcomes and performed a futility analysis to determine the sample size necessary for potential statistical significance for the changes noted. Thirty-nine patients were randomized to the control group and 58 to the PE group with a 6-month follow-up. The baseline characteristics of these 2 groups were similar including serum creatinine, dialysis dependence, age, gender, serum calcium, serum albumin, 24 -hour urine for protein levels and Durie-Salmon myeloma staging. Thirteen (33.3%) of the control group and 19 (33.3%) of the PE group died within 6 months of follow up. Ten patients (31%) in the control and 10 patients (21%) in the PE arm were dialysis dependent at 6 months. Seven patients (47%) came off dialysis in the control and 13 patients (59%) in the PE arm with the mean number of dialysis days from 0–6 months being 45.7±67.6 in the control versus 29.2±56.1 in the PE arm at 6 months. The mean serum creatinine in the control group was 314.6±256.1 μmol/L versus 215.4±215.3 μmol/L in the PE group and the composite end point of death, dialysis or serum creatinine >254 μmol/L occurred in 12 (30.8%) in the control and 11 (19.3%) in the PE arm. The futility analysis to indicate the per group sample size necessary to achieve statistical significance at 6 months for the difference we observed was infinite for cumulative mortality, 805 for dialysis dependence, 2418 for coming off dialysis, 321 for number of dialysis days, 132 for creatinine difference of 100 μmol/L and for the composite outcome of death, dialysis or creatinine>354 μmol/L, 737. We did not observe a statistically significant difference in mortality or renal morbidity for PE versus no PE in patients with myeloma and rapidly progressive kidney failure.

High Number of Successful Mobilizations Associated with the Use of Plerixafor and Colony Stimulating Factors In Patients with Multiple Myeloma (MM) and Lymphoma Treated at Memorial Sloan-Kettering Cancer Center

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2263-2263
Author(s):  
Nelly G. Adel ◽  
Mathew Sherry ◽  
Stephen J. Harnicar ◽  
Emily Mccullagh ◽  
Heather Landau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Adult Patients ◽  
Stem Cell Mobilization ◽  
Cancer Center ◽  
Published Data ◽  
First Line ◽  
Colony Stimulating Factors ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2263 Background: Autologous stem cell transplantation (ASCT) remains the only curative option for many lymphoma patients and it is an integral component of treatment for patients with multiple myeloma (MM). Stem cell mobilization has most commonly been performed using either chemotherapy and colony-stimulating factors or colony stimulating factors alone. This approach was challenged by the inability to collect enough CD 34 cell count to perform an ASCT. Plerixafor (Mozobil ®) previously known as AMD3100, a selective antagonist of CXCR4, has recently been approved for ASCT mobilization in combination with granulocyte- colony stimulating factor (G-CSF) for both multiple myeloma and lymphoma patients and is effective for patients who failed to mobilize enough CD34 cells with other modalities. Patients and Methods: This retrospective study examines all adult patients with MM and lymphoma who received plerixafor as a mobilization agent for ASCT at Memorial Sloan- Kettering Cancer Center between January 1st, 2009 and August 1st, 2010. Patient's information was obtained from the pharmacy data base and electronic medical records. Data included demographics, diagnosis, first line mobilization regimen, second and third line regimens, doses of plerixafor received, number of pheresis sessions and CD34 cells per kg collected per each session. The primary objective was to determine how many patients failed stem cell collection following mobilization at our center. Results: Fifty-six adult patients with lymphoma (N=23) and MM (N=33) were identified. Patients were excluded if they were treated for a pediatric malignancy or an alternate diagnosis. The average number of pheresis and CD34 cells/kg collected in each group are shown Table 1. Forty-three percent (10/23) patients with lymphoma received plerixafor and G-CSF as the first line option for mobilization and 57% (13/23) received plerixafor and G-CSF after failing other regimens. A total of 5 (22%) patients with lymphoma failed collection following mobilization with plerixafor, 1 as a primary mobilization failure and 4 having failed other mobilization strategies. Thirty-nine percent (13/33) of patients with MM received plerixafor and G-CSF as the first line option for mobilization and 61% (20/33)after failing other regimens, including cyclophosphamide (N=15) and G-CSF alone (N=5). Among the patients mobilized with plerixafor, 6% (2/33) failed collection, 1 who received plerixafor and G-CSF for primary mobilization and only 1 after failing other regimens. Conclusion: In lymphoma and MM patients plerixafor in combination with G-CSF is effective for stem cell mobilization and in this study we report higher success rates than in previously published data. The few number of failures with plerixafor plus G-CSF given as a primary mobilization regimen, supports its use in this setting and is attractive considering that it can reduce patient's exposure to chemotherapy. Disclosures: Matasar: Genzyme Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Modified-CVAD Or Modified-Cbad Compared To High Dose Cyclophosphamide For Peripheral Blood Stem Cell Mobilization In Patients With Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2036-2036
Author(s):  
Suzanne C Gettys ◽  
Alison M Gulbis ◽  
Kaci Wilhelm ◽  
Yvonne T Dinh ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Febrile Neutropenia ◽  
Peripheral Blood Stem Cell ◽  
High Dose ◽  
Time To Progression ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Cell Mobilization

Abstract Background Peripheral blood stem cell (PBSC) mobilization in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) is commonly carried out using growth factors alone. Approximately 10-15% of patients receive chemomobilization, which assists with cytoreduction and improving the cell yield; however, an optimal regimen has not been established. Here we report our experience with three chemomobilization regimens that have been used at our center: i) cyclophosphamide alone (Cy) ii) modified cyclophosphamide, vincristine, doxorubicin, dexamethasone (mCVAD) and iii) modified cyclophosphamide, bortezomib, doxorubicin, dexamethasone (mCBAD). Methods This is a single-center, retrospective chart review of patients with multiple myeloma undergoing mobilization for an auto-HCT with Cy, mCVAD, or mCBAD between January 1, 2006 and September 30, 2012. A total of 120 patients were identified as initiating stem cell mobilization with Cy (n=39), mCVAD (n=66) or mCBAD (n=15) for multiple myeloma within the defined time period. For the purpose of this study, we combined mCVAD and mCBAD into one group (n=81). The primary objective of this study is to compare successful mobilization and collection (≥ 2 x 106 CD34+ cells/kg collected) between high dose Cy (2-4 g/m2 x1) and mCVAD (cyclophosphamide 350 mg/m2 q12h x 4 days, vincristine 0.4mg continuous infusion daily x 4 days, doxorubicin 10 mg/ m2 continuous infusion daily x 4 days, dexamethasone 40 mg IV daily x 4 days) + mCBAD (same as previous, except using bortezomib 1.3 mg/m2 bolus x 4 days instead of vincristine). Secondary objectives include optimal mobilization (≥ 4 x 106 CD34+ cells/kg), median number of leukapheresis sessions required, use of plerixafor, post-transplant time to neutrophil engraftment, disease status at day 100, time to progression, and incidence of febrile neutropenia, hospitalization, and ICU admissions with each mobilization regimen. Results The groups were well-matched with regard to demographic characteristics. [Table] All 120 achieved a successful mobilization (≥ 2 x 106 CD34+ cells/kg collected) and 118 achieved an optimal mobilization (≥ 4 x 106 CD34+ cells/kg collected). There was no significant difference in the number of leukapheresis sessions (median 2, range 1-7) or plerixafor use (20.5% Cy vs. 8.6% mCVAD or mCBAD, p=0.08). There was no significant difference in the incidence of febrile neutropenia (10.3% Cy vs. 12.4% mCVAD or mCBAD, p=1.00), hospital admissions (18% Cy vs. 21% mCVAD or mCBAD, p=0.81), or ICU admissions (0% Cy vs. 1.2% mCVAD or mCBAD, p=1.00) between the groups. All 14 patients who had an episode of febrile neutropenia were hospitalized. One patient in the mCVAD or mCBAD group was admitted to the ICU with sepsis and renal failure, but was eventually discharged. There were no mobilization-related deaths in either study group. There was no significant difference in the time to neutrophil engraftment for the two groups (median 11 days, range 9-13). The median time to progression was 11.8 months in the Cy group and 9.1 months in the mCVAD or mCBAD group. Conclusion Cy, mCVAD or mCBAD can be used for successful PBSC mobilization in patients with multiple myeloma undergoing an auto-HCT without any unexpected toxicity. These approaches may be further evaluated in a randomized, prospective trial. Disclosures: Off Label Use: Cyclophosphamide, mCVAD, and mCBAD will be discussed as mobilization regimens used for patients with multiple myeloma. Vincristine and doxorubicin do not have specific indications for use in multiple myeloma. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees; Millennium: Membership on an entity’s Board of Directors or advisory committees.

scholarly journals Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase--deficient severe combined immunodeficiency disease patients

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 1104-1112 ◽  
Author(s):  
S Sekhsaria ◽  
TA Fleisher ◽  
S Vowells ◽  
M Brown ◽  
J Miller ◽  
...  
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Normal Subjects ◽  
Cell Counts ◽  
Cd34 Cells ◽  
The Mean ◽  
Cell Mobilization ◽  
Immunodeficiency Disease ◽  
Severe Combined Immunodeficiency Disease ◽  
Kinetics Of ◽  
Stimulating Factor

Peripheral blood (PB) CD34+ cells mobilized by granulocyte colony- stimulating factor (G-CSF) administration are potentially useful for transplantation and as a target of gene transfer for therapy of hematopoietic disorders. Efficient harvest and planning for clinical use of PB CD34+ cells ideally requires foreknowledge of the expected mobilization kinetics and yield. We developed a sensitive flow cytometric assay for accurately enumerating CD34+ cells throughout the range seen at baseline to peak mobilization. We used this assay to assess the kinetics of G-CSF-mediated mobilization of CD34+ cells to PB in normal volunteers and in patients with chronic granulomatous disease (CGD) or adenosine deaminase (ADA)-deficient severe combined immunodeficiency disease (SCID). Two dose levels of G-CSF were examined (5 and 10 micrograms/kg/d for 7 days). Both doses were well tolerated. For normal subjects and patients an increase in PB CD34+ cells was first detected only preceding the third dose of G-CSF (day 3), peaked transiently on day 5 or 6, and then decreased thereafter despite additional doses of G-CSF. With 32 normal volunteers mean peak CD34+ cell counts were 57 and 76 cells/mm2 of blood (5 and 10 micrograms doses, respectively), whereas for 18 CGD patients the mean peaks were 31 and 40 cells/mm2 of blood. For 2 ADA-deficient SCID patients studied at a G-CSF dose of 5 micrograms/kg/d, the average peak was 16 cells/mm2 of blood. For both of these patient groups mobilization of CD34+ cells to PB was impaired compared with similarly treated normal subjects (P < .05). By contrast to the kinetics of the CD34+ cell mobilization, the absolute neutrophil count (ANC) increased markedly by 6 hours after the first dose of G-CSF and then increased steadily through day 8. At days 5 and 6 (peak mobilization of CD34+ cells) the mean ANC of CGD and ADA patients was only slightly lower ( < or = 15%) than that seen with normal subjects, whereas the difference in CD34+ cell mobilization was > 48%. Thus, ANC is not a reliable surrogate to predict peak PB CD34+ cell counts and direct enumeration of PB CD34+ counts should be undertaken in decisions regarding timing and duration of apheresis to harvest a specific number of these cells. Finally, unexpected, but significant differences in the PB CD34+ cell mobilization between normal subjects and patients with inherited disorders can occur and underscores the importance of establishing the expected mobilization of PB CD34+ cells in the planning of treatment approaches using these cells.

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