High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma

2001 ◽  
Vol 40 (06) ◽  
pp. 215-220 ◽  
Author(s):  
S. Bielack ◽  
S. Flege ◽  
J. Eckardt ◽  
J. Sciuk ◽  
H. Jürgens ◽  
...  

Summary Purpose: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Patients and Methods: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. Results: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5173-5173
Author(s):  
Deok-Hwan Yang ◽  
Je-Jung Lee ◽  
Yeo-Kyeoung Kim ◽  
Jin-Ho Baek ◽  
Sang-Kyun Sohn ◽  
...  

Abstract In the treatment of multiple myeloma (MM), autologous peripheral blood stem cell (PBSC)-supported high-dose melphalan is now considered standard therapy, especially for younger patients. Before PBSC, a new immunomodulatory drug, thalidomide, has replaced VAD regimen as the induction therapy of choice prior to hematopoietic stem cell procurement. Thalidomide has alternative mechanisms of action and usually combines with dexamethasone or alkylating agent, but the optimal doses and the intervals of chemotherapy has been evaluated. We reported preliminary data that the patients with previously untreated multiple myeloma were treated by combined different dose-scheduled thalidomide, cyclophosphamide, and dexamethasone as primary therapy and performed autologous stem cell collection. A total of 52 patients with MM were initially treated thalidomide-based chemotherapy from June 2003. Thalidomide was given with the three different method: 400mg/day on D1–5, D15–19 (arm A), 50mg/day daily (arm B) combined with cyclophosphamide 150mg/m2 P.O. on D1–4 and dexamethasone 20mg/m2 P.O. or I.V. on D1–5, D15–19, or thalidomide 200mg/day daily combined with dexamethasone 20mg/m2 on D1–4, 9–12, 17–20 in odd cycles and on D1–4 in even cycles (arm C), repeated every 28 days. Low-dose aspirin or warfarin was taken as prophylaxis for thrombosis. Thirty-nine (arm A: 17, arm B: 12, arm C: 10) of the 52 patients who received at least 4 cycles or more were evaluated for response and toxicity. Median age was 65 (range: 39–80) years and the total number of 158 cycles of toxicities were evaluated. After median 4 months of time to response followed, the overall response rate was 71.8% (76.5% v 75.0% v 60.0%), including 23% (17.5% v 23% v 28%) of complete or near complete response. Two patients (5.1%) died due to infection during treatment. When the toxicity of therapy was evaluated with more Grade III, two patients (5.1%) showed neurotoxicity, six patients (15.4%) showed neutropenia, and two patients (5.1%) had deep-vein thrombosis. Thirteen patients who achieved more than partial response proceeded to PBSC collection and yielded a median number of 3.78 x 106 CD 34+ cells/kg. This low or intermediate dose or periodic thalidomide combination showed positive responses, reducing toxicities, and adequate numbers of blood stem cells in patients eligible for subsequent high-dose chemotherapy.


1998 ◽  
Vol 16 (2) ◽  
pp. 610-615 ◽  
Author(s):  
M J Egorin ◽  
D M Rosen ◽  
R Sridhara ◽  
L Sensenbrenner ◽  
M Cottler-Fox

PURPOSE Dimethylsulfoxide (DMSO) is used to cryopreserve hematopoietic stem cells and is obligatorily infused into patients who receive stem-cell transplants. This study characterized the plasma concentrations and pharmacokinetics of DMSO and its metabolites in patients who underwent peripheral-blood stem-cell transplants. MATERIALS AND METHODS Plasma concentrations of DMSO, dimethylsulfone (DMSO2), and dimethylsulfide (DMSH2) were assessed in 10 patients who underwent autologous transplants with stem cells, cryopreserved in 10% DMSO (vol/vol). Blood was sampled at multiple times after the stem-cell infusion. Urine was pooled during the 24 hours postinfusion. DMSO, DMSO2, and DMSH2 were assayed simultaneously by gas chromatography. A one-compartment model with saturable elimination proved most suitable for fitting plasma DMSO concentration-versus-time data. RESULTS Stem-cell volumes infused ranged between 180 and 585 mL (254 to 824 mmol DMSO). Infusions lasted between 20 and 120 minutes. Peak plasma DMSO concentrations were 19.1 +/- 6.3 mmol/L (mean +/- SD). Pharmacokinetic parameters for volume of the central compartment (Vc), maximum velocity (Vmax), and Michaels-Menten constant (Km) were 37.3 +/- 17 L, 0.99 +/- 0.57 mmol/L/h, and 5.2 +/- 5.0 mmol/L, respectively. Plasma DMSO2 concentrations increased during the first 24 hours, plateaued at 4.4 +/- 1.2 mmol/L, and remained there until 48 hours (the last sample). DMSH2 concentrations were at steady-state by 5 minutes and remained between 3 and 5 mmol/L for 48 hours. Urinary excretion of DMSO and DMSO2 accounted for 44% +/- 4% and 4% +/- 1%, respectively, of the administered DMSO dose. Renal clearance of DMSO was 14.1 +/- 3.4 mL/min. CONCLUSION These data (1) document plasma concentrations of DMSO and metabolites in patients following peripheral-blood stem-cell transplants; (2) allow consideration of potential effects of these concentrations on stem-cell engraftment and drug-drug interactions; and (3) can facilitate a concentration-guided phase I trial of DMSO.


Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6411-6416 ◽  
Author(s):  
Martin Körbling ◽  
Emil J Freireich

Abstract Peripheral blood stem cell transplantation (PBSCT) is the most common transplantation procedure performed in medicine. Its clinical introduction in 1986 replaced BM as a stem-cell source to approximately 100% in the autologous and to approximately 75% in the allogeneic transplantation setting. This historical overview provides a brief insight into the discovery of circulating hematopoietic stem cells in the early 1960s, the development of apheresis technology, the discovery of hematopoietic growth factors and small molecule CXCR4 antagonist for stem- cell mobilization, and in vivo experimental transplantation studies that eventually led to clinical PBSCT. Also mentioned are the controversies surrounding the engraftment potential of circulating stem cells before acceptance as a clinical modality. Clinical trials comparing the outcome of PBSCT with BM transplantation, registry data analyses, and the role of the National Marrow Donor Program (NMDP) in promoting unrelated blood stem-cell donation are addressed.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4047-4047
Author(s):  
Timoleon Anguita ◽  
Alexandre Chiattone ◽  
Nelson Hamerschlak ◽  
Rima M Saliba ◽  
XiaoWen Tang ◽  
...  

Abstract Abstract 4047 Stem Cell collection via apheresis is the preferred method of collecting stem cells for hematopoietic stem cell transplantation. Accurate prediction of stem cell yield is important for the planning of apheresis procedures and for the collection of adequate stem cells. Pierelli et. al. (Vox Sanguinis 2006, 91; 126) proposed a mathematical formula to estimate the CD34+ dose collected on 1st day of apheresis based on the peripheral blood (PB) CD34+ concentration pre-apheresis and the blood volume processed (BVP). Patients and Methods : We tested the predictive value of this formula in a multicenter sample of 1608 apheresis procedures performed at 5 centers (SCSP n=85, CAS n=195, HIAE n=305, China n=172, MDACC n=851). A 50% randomly selected sample of the MDACC study population was included in this analysis. Each contributing institution selected all consecutive apheresis procedures performed over a designated time frame. Baseline patient characteristics were collected including age, gender, diagnosis, mobilization regimen, complete blood counts on day of collection, and the absolute PB CD34+ counts within 24 hours of the first apheresis procedure. Subjects who did not have data on the PB CD34+ counts were not included in the analysis. Information on total BVP and CD34+ cells collected/kg was also collected. There were 694 males (59%), median age was 50 years. To facilitate comparison of results, we used the same statistical methods reported by Pierelli et. al. to assess the correlation between the actual (ay) and predicted (py) CD34+ yields, including assessment of the linear correlation between these measures and the distribution of the ay/py ratio. Results: Data on both actual and predicted yields were available for 1148 (97%) records. Overall, Pearson's correlation coefficient (r) between ay and py was 0.67, ranging from 0.67 for MDACC to 0.86 for China and CAS. Median ay/py ratio was 1.1 (0.02–433) ranging from 0.99 for HIAE to 1.5 for China and CAS. To characterize the correlation between ay and py and facilitate the clinical application of our findings, we classified the actual and predicted yields as falling below (<2), within (2–5), or above (>5) the conventionally acceptable collected CD34+ doses (x106/Kg). Positive predictive value (PPV) of py was estimated considering the distribution of ay as the “gold standard”. PPV was relatively high for py >5 [85% (95% CI 81–89%)], average for py <2 [72% (95% CI 68–76%)], and low for py between 2 and 5 [56% (95% CI 51–62%)]. This pattern was consistent across institutions. PPV ranged from 55% (SCSP) to 80% (China) for py<2; from 37% (CAS) to 68% (MDACC) for py between 2 and 5, and from 73% to 94% for py>5, exceeding 80% at all institutions except SCSP. Overall, 13% of cases predicted to have a CD34+ yield between 2 and 5, had an actual yield <2. This proportion varied across institutions ranging from 5% at SCSP to 28% at HIAE. Notably, the distribution of BVP (ml/Kg) was comparable across the 3 categories of ay defined above with a median of 204 (range 74–263). Consistent pattern was also observed within institutions. Conclusion: Our data indicate that the formula of Pierelli et.al. is associated with high PPV for predicted CD34+ doses >5, acceptable PPV for doses<2, and relatively low PPV for doses falling between 2 and 5. The data also suggests that CD34+ yields correlate with pre-apheresis CD34+ count and are independent of BVPNTotal 1182rangeSCSP 85rangeCAS 195rangeChina 172rangeHIAE 305rangeMDACC 425rangeAbsolute PB CD34+ × 106/μl (median, range)280.3–2735314.2–279251.3–1750140.3–411310.6–604312–2735Weight, Kg (median, range)729–1696738–143619–1106322–1007313–1438411–169Day 1 Blood volume processed, L (median, range)153–131148–25123–299.54.5–12.5195–131168–27Actual Day 1 CD34+ dose (x 106/Kg), (median, range)2.90.01–1092.90.2–293.80.01–1091.80.01–503.50.1–442.80.2–101<236%27%33%53%34%33%2–531%40%28%20%27%39%>533%33%38%27%39%28%Predicted Day 1 CD34+ dose (× 106/Kg), (median, range)2.40.02–2112.60.3–242.20.1–730.960.02–253.20.1–672.40.1–211<244%45%44%63%33%42%2–530%25%37%17%28%35%>527%30%19%20%38%23%Ratio CD34+ dose collected/predicted1.10.02–4331.10.2–111.50.03–6.31.50.02–4330.990.04–121.10.1–9.9Pearson's correlation coefficient0.670.830.860.860.770.67Pearson's within Predicted Day 1 dose<20.420.080.630.50.570.282–50.280.250.280.20.360.25>50.560.770.810.70.630.6 Disclosures: No relevant conflicts of interest to declare.


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