NON Cryopreserved Hematopoietic STEM CELLS to Autograft Patients with Lymphomas: A PAIR Matched Analysis Comparing a Single Center Experience to the Use of Cryopreserved STEM CELLS Reported to the EBMT Registry

Introduction: Around fifty thousand autologous stem cell transplantations are done each year worldwide, using cryopreserved peripheral blood stem cells (PBSC). Cryopreservation is time consuming and expensive. Since 2007, several retrospective studies have shown that PBSC can be stored at 4Dg C for two to three days, allowing autologous stem cell transplantation (ASCT) in patients with multiple myeloma receiving high dose melphalan. Data with non-cryopreserved PBSC in patients autografted for lymphoma following longer preconditioning regimens are limited. In addition, there has been no controlled comparison able to possibly detect unforeseen differences. Patients and methods: We compared outcomes of 94 consecutive adult patients with lymphomas (66 with Hodgkin Lymphoma) autografted in our department in Oran (Algeria), using PBSC stored at 4 dg C, from 2009 to 2018 with patients receiving cryopreserved stem cells reported to the EBMT registry. Patient's autografted in Oran were matched with patients receiving cryopreserved PBSC in the registry (4 controls per Oran Patient). Results: Neutrophil engraftment was significantly faster with cryopreserved PBSC (p= 0.003): by day 10, only 17% of patients receiving non-cryopreserved PBSC engrafted versus 48% for cryopreserved PBSC. Likewise, platelet recovery to 20 000/mm3 was significantly faster in patients receiving cryopreserved PBSC (p=0.01). However, all patients in both groups had recovered by day 20. There were no significant differences in Non Relapse Mortality (9% versus 7%; p=0.4), Relapse Incidence (22% versus 32%; p=0.13), Progression Free Survival (70% versus 61%; 0.4) or Overall Survival (85% versus 75%; p=0.3). Conclusion: This analysis suggests that, in patients with lymphomas receiving pretransplant regimens such as the BEAM, PBSC stored at 4dg C for up to six days can be used safely in centers with no cryopreservation facility. The kinetics of recovery of hematopoiesis however did show a significant, albeit small, delay of engraftment for both neutrophils and platelets, which favors the use of cryopreservation if available. Disclosures Blaise: Jazz Pharmaceuticals: Honoraria. Peggs:Autolus: Consultancy. Salles:Karyopharm: Consultancy; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Bristol Myers Squibb: Consultancy, Other; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Autolus: Consultancy; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Genmab: Consultancy; Novartis: Consultancy, Honoraria, Other; Kite: Consultancy, Honoraria, Other; Takeda: Consultancy, Honoraria, Other; Debiopharm: Consultancy; Amgen: Honoraria, Other: Participation in educational events; MorphoSys: Consultancy, Honoraria, Other; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Epizyme: Consultancy. Milpied:Roche: Honoraria, Other: Travel support; Astellas: Honoraria; Sandoz: Honoraria, Other: consultancy or advisory role; Janssen: Honoraria; Gilead Sciences: Other: consultancy or advisory role; Celgene: Other: Travel support.

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44 Success of stem cell collection and neutrophil recovery in pediatric patients with brain tumours

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2018.284 ◽

2018 ◽

Vol 45 (S3) ◽

pp. S9-S9

Author(s):

George Michaiel ◽

Tony Truong ◽

Nicole Prokopishyn ◽

Henry Luu ◽

Lucie Lafay-Cousin ◽

...

Keyword(s):

Stem Cell ◽

Peripheral Blood ◽

Brain Tumours ◽

Pediatric Patients ◽

High Dose ◽

Cell Transplant ◽

Peripheral Blood Stem Cells ◽

Hematopoietic Stem ◽

Platelet Recovery ◽

Stem Cell Collection

BACKGROUND: The use of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplant (HSCT) has been used in certain pediatric patients with brain tumours to delay/spare radiotherapy. We aimed to study factors predicting a successful stem cell collection (SCC) and correlate stem cell dose infused with HSCT outcomes. METHODS: A retrospective chart review was undertaken for pediatric patients with brain tumours treated at our centre with HDC/HSCT between 2004-2016. RESULTS: Fifty-five patients were identified (32 male) with median age of 6.3 years at time of SCC (range 0.4-18.7). Patients' diagnoses were medulloblastoma (62%), ATRT (20%), and PNET (18%). Most patients (82%) underwent a single/1-day SCC, while the remaining required 2 SCC procedures. Peripheral blood stem cells were the source in most collections (95%). Successful SCC (CD34 collected greater-than-or-equal-to 2 x10^6/kg/transplant) and ideal SCC (greater-than-or-equal-to 5 x10^6/kg/transplant) was achieved in 85% and 45% of patients, respectively. Use of mobilizing chemotherapy with G-CSF was the only factor associated with achieving an ideal collection, while gender, age, stem cell source, and pre-apheresis peripheral blood CD34 count were not significant. Higher CD34/kg infused was associated with faster neutrophil engraftment in the first 3 courses of HDC/HSCT and platelet engraftment in the first course. CONCLUSIONS: The majority of SCC for autologous HSCT can be successfully completed with a single apheresis session. Mobilization with both chemotherapy and G-CSF yields higher CD34 compared to G-CSF alone. Higher dose of CD34/kg infused was associated with faster neutrophil and to a more limited scale platelet recovery post-HSCT.

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Short-Term Noncryopreserved Hematopoietic Stem Cells: Single Center Experience of Autologous Transplantation

Blood ◽

10.1182/blood-2019-131695 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5636-5636

Author(s):

Sergei Voloshin ◽

Andrey Garifullin ◽

Anastasiya Kuzyaeva ◽

Vasily Shuvaev ◽

Alexander Schmidt ◽

...

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Autologous Transplantation ◽

Length Of Hospital Stay ◽

High Dose Chemotherapy ◽

High Dose ◽

Peripheral Blood Stem Cells ◽

Hematopoietic Stem ◽

Female Ratio ◽

Single Center Experience

Background: High-dose chemotherapy (HDCT) followed by autologous transplantation of hematopoietic stem cells (auto-HSCT) is an important component of treatment in multiple myeloma (MM). There is a standard method of controlled cryopreservation of HSC suspension. We found that the storage of native HSC suspension with temperature fluctuations from +3 °C to +5 °C during 72 - 120 hours does not significantly affect the content of CD34+ cells in the product, the index 7AAD- (7-AAD (7-aminoactinomycin - D) is a fluorescent marker that penetrates damaged cell membranes and binds to double-stranded DNA. Through 7AAD does not penetrate intact membranes, so living cells are not stained 7AAD with flow cytometry), and colony-forming ability (CFA) of HSC, as well as the recovery time of hematopoiesis in MM patients after auto-HSCT. Aim: To evaluate the effectiveness and safety of the method of storage of non-cryopreserved peripheral blood stem cells. Methods: 39 patients with MM were included in this study(male/female ratio 1.36:1). All the patients get standard immunochemotherapy programs and were in remission at the time of auto-HSCT. Patients were divided into two groups depending on the method of stem cell storage: group 1 - non-cryopreserved (n=20), group 2 - cryopreserved (standard) (n=19). An effectivity and safety were evaluated in such parameters as the number of CD34+ and 7AAD- cells, CFA after apheresis and before reinfusion of HSC. Also, we evaluated the number of platelets concentrate transfusions, the timing of engraftment of granulocytic and megakaryocytic blood sprouts, the length of hospital stays after auto-HSCT. Results: The results are presented in the comparison table of the evaluated parameters. Our data showed significantly reduce of episodes febrile neutropenia and cases of enteropathy. Conclusion: Thus, the proposed method of storage of HSC is not inferior to the traditional method with cryopreservation on such parameters as CD34+, 7AAD-, CFA, the number of platelets concentrate transfusions, terms of hematopoiesis restoration, length of hospital stay after HSCT, the number of complications. Table. Disclosures Shuvaev: Fusion Pharma: Consultancy; BMS: Consultancy; Novartis: Consultancy; Pfize: Honoraria.

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Successful Harvesting of Peripheral Hematopoietic Stem Cells after Induction Treatment with Bortezomib, Adriamycin, Dexamethasone (PAD) in Patients with Newly Diagnosed Multiple Myeloma (MM)

Blood ◽

10.1182/blood.v112.11.3470.3470 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3470-3470 ◽

Cited By ~ 3

Author(s):

Hartmut Goldschmidt ◽

Henk M. Lokhorst ◽

Uta Bertsch ◽

Bronno van der Holt ◽

Laila el Jarari ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Progression Free Survival ◽

Phase Iii ◽

Induction Treatment ◽

High Dose ◽

Newly Diagnosed ◽

Hematopoietic Stem ◽

Cell Harvesting

Abstract The HOVON-65/GMMG-HD4 trial is a prospective, randomized phase III trial to evaluate the efficacy of bortezomib prior to high-dose melphalan (200 mg/m2, HDM) on response and progression-free survival (PFS) in patients with newly diagnosed MM stage II or III according to Salmon & Durie (SD). Until May 2008 in total 833 patients aged 18–65 years were included in the trial. Patients were randomized to receive three cycles of VAD (arm A; vincristin 0,4mg, days 1–4, adriamycin 9 mg/m2, days 1–4, dexamethasone 40 mg, days 1–4, 9–12, and 17–20) or PAD (arm B; bortezomib 1.3 mg/m2, days 1,4,8,11, adriamycin 9 mg/m2, days 1–4, dexamethasone 40 mg, days 1–4, 9–12, and 17–20). Hematopoietic stem cells were mobilized in patients using the CAD regimen (cyclophosphamide 1000 mg/m2 iv day 1, adriamycin 15mg/m2, days 1–4, dexamethasone 40mg, days 1–4) and G-CSF. After stem cell harvesting all patients received one or two cycles of HDM with autologous stem cell transplantation followed by maintenance therapy with thalidomide 50 mg daily (arm A) and bortezomib 1.3 mg/m2 once every 2 weeks (arm B), respectively. As of August 2008 stem cell harvesting data from the first consecutively enrolled 150 patients (75 per arm) were analyzed. The data of the initial 300 patients (150 per arm) will be available by November 2008. Both treatment arms did not differ in age, SD stage of disease, ISS stage, and FISH abnormalities. 132 patients (88%) were treated with CAD plus G-CSF. Dosing and type of G-CSF treatment were comparable in both arms. In all patients stem cell collection was successful and at least two autografts could be harvested (minimal number of stem cells permitted per autograft was 2.0 ×106 CD 34+ cells per kg BW). Induction treatment Days until first leukapheresis Median (range) Number of leukaphereses Median (range) Number of harvested CD34+ stem cells (× 106) per kg BW Median (range) PAD 110 (96–149) 1 (1–4) 10.5 (4.1–37.6) VAD 111 (95–156) 1 (1–5) 9.3 (4.0–37.0) In 64% of the patients in arm A (VAD) and 79% of the patients in arm B (PAD) only one leukapheresis was sufficient for stem cell harvesting. In all patients hematopoietic reconstitution was achieved after HDM followed by autografts harvested after PAD or VAD. We conclude that stem cell harvesting after PAD is very well feasible.

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Effect of Pharmacokinetic Variability on the Toxicity and Efficacy of High-Dose Melphalan for Multiple Myeloma

Blood ◽

10.1182/blood.v116.21.1349.1349 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1349-1349 ◽

Cited By ~ 1

Author(s):

Dan T. Vogl ◽

Eric Stoopler ◽

Lisa Davis ◽

Thomas M. Paul ◽

German Salazar ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Oral Mucositis ◽

Drug Exposure ◽

High Dose ◽

Hematopoietic Stem ◽

Platelet Recovery ◽

Unit Increase ◽

High Dose Melphalan ◽

Severe Mucositis

Abstract Abstract 1349 Background: High dose melphalan is the most common conditioning regimen for patients undergoing autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma (MM). However, toxicity and efficacy of this treatment are variable, with the sources of variability poorly understood. We hypothesized that variation in melphalan pharmacokinetics would explain differences in outcomes after transplant. Methods: We evaluated 41 patients with MM undergoing ASCT with high-dose melphalan conditioning. Patients received melphalan on day -2 at a dose of 200 mg/m2 (one patient with poor renal function received 180 mg/m2) and ASCT on day 0. Melphalan dose was calculated using ideal body weight (IBW), with adjusted IBW used for patients weighing >120% of IBW. We assessed toxicity on day +7 using the Oral Mucositis Assessment Scale (OMAS), a physician evaluated measurement of erythema and ulceration (on a scale of 0–5, with higher scores indicating more severe mucositis). Patients reported the severity of mouth soreness on a scale of 0–10 using the Mucositis Daily Questionnaire (MDQ) on days 0, +3, +7, +11, +19, and +28. Melphalan concentrations were measured using HPLC/tandem mass spectrometry in plasma samples obtained during infusion and 2, 4, 8, 15, and 30 minutes, and 1, 2, 3.5, 8, and 14 hours after its completion, as well as immediately prior to stem cell infusion. Melphalan area under the curve (AUC) was estimated by non-compartmental analysis. Results: Patients' median age was 57 years (range 39–72); 59% were male. We observed significant variation in melphalan exposure, with a range of 7.6–26.6 mg*h/L (median 13.5). Severity of oral mucositis was directly related to AUC (with an increase of 0.1 on the OMAS score for every 1 unit increase in AUC, p=0.003). The most severe mucositis was seen in the 4 patients with an AUC ≥17.5 (75% had OMAS scores >1), while severe mucositis was rarely seen in the 18 patients with AUC ≤12.5 (only 1 of 18 had an OMAS score >1). The association between AUC and maximum reported mouth soreness was not statistically significant (an increase of 0.2 on the MDQ scale for every 1 unit increase in AUC, p=0.17), but there was a trend toward higher maximum reported mouth soreness in the 4 patients with AUC≥17.5 (mean 7.5 vs. 4 for other patients, p=0.07). Eight patients had detectable melphalan concentrations at the time of stem cell infusion (mean 3.8 ng/mL, range 1.8–7.1), though time to neutrophil and platelet recovery did not differ for these patients compared with those with undetectable melphalan levels. Of 19 patients with measurable disease at the time of transplant, 8 had stable disease (SD), 9 partial response (PR), and 2 complete response (CR) at day +100. The 2 patients with CR had higher melphalan exposure than patients without a CR (mean AUC 19 vs 11.6, p= 0.002), but there was no discernable difference in melphalan levels between patients with a PR or SD. Conclusion: Using standard dosing calculations in a representative sample of patients with myeloma, melphalan drug exposure was highly varied. Drug exposure was correlated with severity of oral mucositis, and complete responses were seen only in patients with high drug exposure. Further analyses are planned into the effect of obesity and renal dysfunction on pharmacokinetics. Exploration of the appropriate target AUC and strategies for reducing variability in drug exposure have the potential to improve both efficacy and toxicity of this effective and commonly used therapy. Disclosures: No relevant conflicts of interest to declare.

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

Nuklearmedizin ◽

10.1055/s-0038-1625284 ◽

2001 ◽

Vol 40 (06) ◽

pp. 215-220 ◽

Cited By ~ 33

Author(s):

S. Bielack ◽

S. Flege ◽

J. Eckardt ◽

J. Sciuk ◽

H. Jürgens ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

High Activity ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

High Dose ◽

External Radiotherapy ◽

Primary Tumor Site ◽

Hematopoietic Stem

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.

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