Leakage Radiometric Control of Chemical Drugs with Regional Perfusion of Surgical Isolated Limbs

2019 ◽  
pp. 32-38
Author(s):  
Б. Наркевич ◽  
B. Narkevich ◽  
С. Ширяев ◽  
S. Shiryaev ◽  
И. Лагутина ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Clinical Effectiveness ◽  
High Dose Chemotherapy ◽  
Regional Perfusion ◽  
High Dose ◽  
Inhalation Anesthesia ◽  
Chemotherapy Drug ◽  
Upper And Lower Extremities ◽  
99Mtc Activity

Purpose: Modernization and evaluation of the clinical effectiveness of the technology of continuous radiometric monitoring carried out during high-dose chemotherapy of a surgically isolated limb with tumor foci. Material and methods: A modernized radiometric control technology for regional limb perfusion is proposed. It is based on in vivo labeling of erythrocytes with 99mTc eluate followed by continuous monitoring of the activity of labeled erythrocytes as a simulator of a chemotherapy drug over the heart region. Its distinctive features are intravenous injection of a pyrfotech slice after giving inhalation anesthesia to ensure a sufficient level of red blood cell chelation, as well as using 99mTc activity less than its minimum significant level, which allows working with an open source of ionizing radiation without violating the requirements of radiation safety regulations. Results: The developed technology was successfully used with 106 regional perfusion of the upper and lower extremities in patients with melanoma or sarcoma of soft tissues. In 4 cases, according to the results of radiometric control, the intervention of the surgical team was required to reduce the chemical preparation leakage that was occurring. Conclusion: The technology upgraded by us is characterized by ease of implementation, the ability to take timely measures to prevent or reduce the leakage of a chemotherapy drug from an isolated limb according to the results of continuous in vivo radiometric monitoring of 99mTc-labeled red blood cells over the heart, as well as low radiation load on the patient and staff.

scholarly journals Efficacy and safety of high-dose chemotherapy with in vivo purged auto-SCT in relapsed follicular lymphoma: long-term follow-up

2009 ◽  
Vol 45 (6) ◽  
pp. 1119-1120 ◽  
Author(s):  
M Magni ◽  
M Di Nicola ◽  
C Carlo-Stella ◽  
L Devizzi ◽  
A Guidetti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Efficacy And Safety ◽  
Long Term Follow Up

The Utility of Consolidative Upfront High Dose Chemoradiotherapy and ASCT in Patients with Mantle Cell Lymphoma (MCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2072-2072
Author(s):  
Daniel Persky ◽  
Carol S. Portlock ◽  
Simone Lessac-Chenen ◽  
Alexia Iasonos ◽  
Andrew D. Zelenetz ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Significant Difference ◽  
Dose Dense

Abstract Introduction: Two approaches to improve progression-free survival (PFS) in MCL are intensifying induction, as with hyperCVAD/M-A regimen, or intensifying consolidation with high dose chemoradiotherapy (HDT) and ASCT as in the prospective European MCL Network Trial. At MSKCC the strategy is to incorporate both approaches by administering an anthracycline-containing regimen in a dose dense fashion (CHOP- or R-CHOP-14) followed by consolidation with ICE (ifosfamide, carboplatin, etoposide) and HDT/ASCT. Patients: Forty six patients with newly diagnosed MCL underwent HDT/ASCT between 11/96 and 2/05. The median age was 55 years; 74% were male; 72% had bone marrow involvement, 39% had GI involvement, 7% were in leukemic phase, and 91% presented with stage IV disease. Splenomegaly was seen in 35%, B symptoms in 9%, KPS>70 in 93%, elevated LDH in 23%, and blastoid histology in 9%. Results: Induction was 4 to 6 cycles of CHOP-14 (43%), R-CHOP-14 (37%), or other doxorubicin-containing regimen (20%). Consolidation was performed with 2–3 cycles of ICE in 53% or R-ICE in 39%. Upfront treatment was well tolerated and permitted adequate stem cell collection and prompt transition to HDT/ASCT. Conditioning regimens were TBI/CY/VP-16 (59%) and BEAM (41%). Involved field radiation therapy was administered to 65%. Post-ASCT rituximab maintenance was given to 39%, with 57% of patients receiving rituximab as part of their treatment. Anthracycline-based induction led to CRu of 44% and ORR of 98%. Seventy two percent of patients were transplanted in CR, while the remaining 28% were in PR. At a median follow-up of 2.5 years (range 0.4–8.0 years) 17% of the patients have died and 24% have had progressive disease. The median OS and PFS have not been reached (lower 95% CI, 5.7 years and 4.4 years, respectively). The 5-year PFS and OS are 58% and 83%, respectively. The use of rituximab at any point during treatment prolonged PFS - only 1 of 26 patients receiving rituximab relapsed, as compared to 10 of 20 patients who were rituximab naive (p=0.03); thus far there is no significant difference in OS. There was no day 100 treatment related mortality. One patient developed bronchiolitis obliterans after ASCT and died of pulmonary fibrosis 6.5 years later; 3 patients have died of secondary cancers - one case each of MDS (1.6 years after ASCT), melanoma and lung cancer. Conclusion: These data provide evidence that dose-dense induction with CHOP-14 or R-CHOP-14 and consolidation with ICE/HDT/ASCT appears to be safe and effective, with minimal acute toxicity. Although the median follow-up is short, the use of rituximab appears to improve PFS. This contrasts with the findings of German LGLSG and may be a consequence of in vivo rituximab purging. Future therapy could incorporate all the successful elements of prior treatment programs, including R-CHOP-14, R-ICE, and radioimmunotherapy with high dose chemotherapy conditioning regimen, followed by ASCT and rituximab-based maintenance. PFS stratified by Rituximab PFS stratified by Rituximab

scholarly journals Detection of leukemic clone maturation in vivo by premature chromosome condensation

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 1950-1960
Author(s):  
WN Hittelman ◽  
P Agbor ◽  
I Petkovic ◽  
B Andersson ◽  
H Kantarjian ◽  
...  
Keyword(s):  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
High Dose Chemotherapy ◽  
Chromosome Condensation ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Premature Chromosome Condensation ◽  
Leukemic Clone

The purpose of this study was to determine the feasibility of using the technique of premature chromosome condensation to detect the in vivo maturation of abnormal elements in patients with chronic myelogenous leukemia (CML), myelodysplastic syndrome, and acute leukemia. Patients were chosen for study if there were a clinical suggestion of in vivo maturation and a leukemic clone exhibiting a distinguishable karyotypic abnormality. Mature peripheral blood granulocytes were enriched by two- step Ficoll-Hypaque gradient sedimentation and fused with mitotic Chinese hamster ovary cells to induce the formation of prematurely condensed chromosomes (PCC). These PCC were then analyzed for chromosome number per cell (in the case of patients with a numerical abnormality) or by G-banding (in the case of specific translocations). Of 13 patients chosen for study, 12 showed karyotypic evidence for maturation of the abnormal elements in vivo. Maturation was observed in a number of clinical situations including before treatment in benign CML and myelodysplasia, after low-dose and high-dose chemotherapy in myelodysplasia and acute myelogenous leukemia (AML), and in remission. These results suggest that the technique of premature chromosome condensation can be a powerful tool in better understanding the biology of disease and mode of response to therapy in vivo in patients with leukemia and preleukemic syndromes, especially during treatment with agents thought to induce maturation of the leukemic elements.

The Addition of Rituximab and/or Alpha-Interferon to High Dose Chemotherapy and Autologous Stem Cell Transplantation for Patients with Relapsed Follicular Lymphoma Produces Durable Progression Free Survival and Molecular Remissions

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1357-1357 ◽  
Author(s):  
Sita Bhella ◽  
Neil L Berinstein ◽  
Nancy Pennell ◽  
Matthew Cheung ◽  
Kevin R. Imrie ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Median Time ◽  
Residual Disease ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Stem Cell Collection

Abstract Abstract 1357 Introduction: High dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is historically effective treatment for patients with relapsed follicular lymphoma (FL) but relapse is common possibly due to contaminated stem cell grafts or inadequate eradication of primary disease. The addition of immunotherapy to HDT/ASCT may augment “in vivo” graft purging and achieve more effective eradication of minimal residual disease (MRD) post ASCT. This may lead to improved PFS and OS. Methods: We conducted 3 sequential prospective phase 2 trials of HDT/ASCT combined with immunotherapy in patients with relapsed FL from 1997–2010. Protocol 1 (n=13) used a-interferon 3 MU/m2 SC TIW for 2 years post ASCT. Protocol 2 (n=23) used a single infusion of rituximab (R) 375 mg/m2 for ‘in vivo’ purging 3–5 days pre-stem cell collection and 2 sets of 4 weekly R at 2 and 6 months post ASCT respectively. Protocol 3 (n=32) used 3 infusions of R 375 mg/m2 pre stem cell collection, followed by a-interferon 3 MU/m2 SC TIW × 2 years + R 375mg/m2 × 6 weekly infusions post ASCT. Eligibility included adult patients age 18–65 with stage III or IV follicular lymphoma grades 1–3a in first or second relapse. Salvage chemotherapy was either CHOP or DHAP depending on prior anthracycline exposure. High dose therapy was cyclophosphamide, carmustine, and etoposide (CBV). Minimal residual disease (MRD) assessment of t(14; 18) by quantitative PCR was serially performed in blood, PBSC and marrow. Studies were REB approved and all patients gave informed consent. Results: Sixty-eight patients from the 3 trials are included. Median age at study enrolment was 47 (30-71) and patients were a median of 31 mo (9-197) from diagnosis. 54% were male. Median FLIPI score was 2. Median # of prior chemotherapies was 1. Median number of cycles of salvage chemotherapy was 4 (2 - 10). 63 patients proceeded to ASCT. 5 patients were not transplanted either do to disease progression (2), or failed stem cell mobilization (3). Baseline characteristics of the patients enrolled in the three trials were similar, with the exception of rituximab(R) exposure in 22% of the patients in Protocol 3. 4 (6%) patients were lost to follow up. Median time to death or last follow was 84.5 mo (7-166). 32 patients (47%) relapsed and 20 (29%) have died. Median follow up times for each trial were 116, 99 and 57 mo. Actuarial median OS for Protocol 1 was 136 mo from enrolment and has not yet been reached for Protocols 2 and 3. Actuarial median PFS for Protocols 1 and 3 are 49 and 78 mo respectively and has not yet been reached for Protocol 2. MRD assessment by PCR was collected on 48 patients. Compared with study 1, the increased use of R pre SC collection improved in vivo purging by 2 logs. In Protocols 1 and 2, most still had detectable disease in the graft to a sensitivity of 1 cell/100,000. In Protocol 3, 56% had MRD negative apheresis products. 91% of 46 evaluable patients achieved molecular remission post stem cell transplant. Thirteen patients (19%) developed secondary malignancies post ASCT with a median time to malignancy of 88.5 mo (39-144). 1 patient developed 2 distinct malignancies. Secondary malignancies present were: MDS (4), AML (1), ALL (1), basal cell carcinoma (2), squamous cell carcinoma (3), thyroid cancer (1), non small cell lung cancer (1) and adenocarcinoma of unknown origin (1). Five (7%) patients transformed to DLBCL, with a median time to transformation post ASCT of 43.5 mo (17-142). The majority of patients who received rituximab immunotherapy pre and post ASCT developed persistent hypogammaglobulinemia. 17 patients (26%) developed interstitial pneumonitis or >2 respiratory complications post rituximab. 4 patients (6%) require monthly IVIG to treat recurrent respiratory infections. 10 patients (15%) developed herpes zoster <90 days post ASCT. 15% and 30% of patients in Protocols 1 and 3 did not complete the 2 years of alpha-IFN post ASCT secondary to one or more of depression, fatigue or cytopenias. Conclusion: HDT + ASCT combined with R +/− a-IFN produces durable PFS and molecular remissions but is associated with prolonged hypogammaglobulinemia and higher rates of interstitial pneumonitis. Three infusions of R pre SC collection achieve higher rates of molecular remission. Compliance with 2 years of a-IFN added to R post ASCT is poor and may not add clinical benefits to R alone. The additional role of HDT/ASCT in the era of R-chemotherapy for FL needs to be explored. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evidence for a novel in vivo control mechanism of granulopoiesis: mature cell-related control of a regulatory growth factor

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1303-1307 ◽  
Author(s):  
JE Layton ◽  
H Hockman ◽  
WP Sheridan ◽  
G Morstyn
Keyword(s):  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Second Phase ◽  
Rapid Reduction ◽  
Disease States ◽  
Clearance Mechanism ◽  
Csf Levels

Abstract As part of phase I/II clinical trials of granulocyte colony-stimulating factor (G-CSF), the pharmacokinetics was studied. To determine the optimal way of abrogating the neutropenia caused by melphalan, patients received G-CSF and melphalan on several schedules. The half-life (t 1/2) of elimination of G-CSF was in the range 1.3 to 4.2 hours and was prolonged at higher doses, suggesting that one clearance mechanism becomes saturated at doses greater than 10 micrograms/kg, When a continuous subcutaneous (SC) infusion was administered for five days, a rapid reduction in serum G-CSF levels occurred during the last two days of the infusion, indicating that an additional clearance mechanism was induced. When a continuous infusion of G-CSF was administered after melphalan, serum G-CSF levels remained constant for a longer period of time but did decrease during the second phase of a biphasic neutrophil response. In another clinical trial, G-CSF was administered after high- dose chemotherapy and autologous bone marrow transplantation (ABMT). In these patients, the G-CSF levels did not decrease while the patients were neutropenic. These results show that increased neutrophil levels are associated with increased clearance of G-CSF. This may be one of the negative feedback mechanisms involved in maintaining neutrophil homeostasis in normal and disease states.

scholarly journals Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3590-3597 ◽  
Author(s):  
A Spencer ◽  
RM Szydlo ◽  
PA Brookes ◽  
E Kaminski ◽  
S Rule ◽  
...  
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Chronic Phase ◽  
High Dose Chemotherapy ◽  
Cell Depletion ◽  
Class I ◽  
High Dose ◽  
T Cell Depletion ◽  
Advanced Phase

Between August 1985 and July 1994, we performed 115 volunteer unrelated donor (VUD) bone marrow transplants (BMT) for first chronic phase (n = 86) or advanced phase (n = 29) chronic myeloid leukemia (CML). Standard serologic HLA typing of potential donors and recipients was supplemented with one-dimensional isoelectric focusing (IEF) for class I proteins, allogenotyping for DR and DQ alleles using DNA restriction fragment length polymorphism (RFLP) analysis, and the measurement of antirecipient major histocompatibility complex (MHC) cytotoxic T- lymphocyte precursor cells in the donors' blood (CTLp assay). Recipients were conditioned for transplantation with a combination of high-dose chemotherapy and total body irradiation (n = 103) or high- dose chemotherapy alone (n = 12). Twenty eight recipients received ex vivo T-cell-depleted marrow, and 84 underwent some form of in vivo T- cell depletion. The probability of severe (grades III or IV) acute graft-versus-host disease (aGVHD) was 24%, and that of extensive chronic graft-versus-host disease (cGVHD), 38%. Proportional hazards regression analysis showed an association between low frequency CTLp and a reduced incidence of severe aGVHD (relative risk [RR], 0.28; P = .0035). The probability of relapse at 3 years was 23%, with first chronic phase disease being independently associated with a lower risk of relapse (RR, 0.71; P = .01). The overall leukemia-free survival (LFS) at 3 years was 37%; the LFS for the first chronic phase and advanced phase recipients was 41% and 26%, respectively. First chronic phase disease (RR, 0.56; P = .063) and the combination of recipient cytomegalovirus (CMV) seronegativity and an IEF-matched donor (RR, 0.48; P = .011) were both associated with improved LFS. The probabilities of survival and LFS for patients under 40 years of age transplanted in first chronic phase from an IEF-matched donor were 73% and 50%, respectively. We conclude that VUD BMT is a reasonable option for patients with CML; when using ex vivo or in vivo T-cell depletion, optimal results are achieved in patients transplanted in chronic phase with marrow from donors without demonstrable class I HLA mismatch and a low CTLp frequency.

Chemotherapy Drug Encapsulated Poly(Lactic-Co-Glycolic Acid) Nanoparticles

2006 ◽  
Author(s):  
A. Champa Jayasuriya ◽  
Anthony Darr ◽  
Nabil A. Ebraheim
Keyword(s):  
Adverse Effects ◽  
Glycolic Acid ◽  
Bone Cancer ◽  
High Dose Chemotherapy ◽  
Plga Nanoparticles ◽  
Cancer Site ◽  
High Dose ◽  
Chemotherapy Drug ◽  
Chemotherapy Drugs

In order to exhibit pharmacological activity at the bone cancer site, high-dose chemotherapy drugs need to be used. This often causes toxicity and unfavorable systemic adverse effects leading to significant problems to the patient. Since nanoparticles are in subcellular size, they can effectively entered to the cell membrane that could result in higher cellular uptake. In this study, we report preparation and characterization of poly(lactic-co-glycolic acid) - PLGA nanoparticles, which encapsulated with chemotherapy drug cisplatin.

scholarly journals Long-Term Remission of Primary Bone Marrow Diffuse Large B-Cell Lymphoma Treated with High-Dose Chemotherapy Rescued byIn VivoRituximab-Purged Autologous Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Hiroshi Kazama ◽  
Masanao Teramura ◽  
Kentaro Yoshinaga ◽  
Akihiro Masuda ◽  
Toshiko Motoji
Keyword(s):  
Bone Marrow ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Primary Bone ◽  
Primary Bone Marrow ◽  
Large B Cell

Primary bone marrow diffuse large B-cell lymphoma (DLBCL) is a rare type of extranodal lymphoma with poor prognosis. Here, we report a case of primary bone marrow DLBCL successfully treated with high-dose chemotherapy and rescued byin vivorituximab-purged autologous stem cells. A 39-year-old woman visited our hospital because of anemia. Bone marrow examination revealed a large B-cell lymphoma invasion. An18F-fluorodeoxyglucose positron emission tomography scan revealed disseminated bone marrow uptake without evidence of dissemination at other sites. These findings led to a diagnosis of primary bone marrow DLBCL. Our patient underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy and achieved complete remission. Subsequently, she received high-dose chemotherapy with anin vivorituximab-purged autologous stem cell transplant. Seven years have passed since the transplantation, and she remains in remission. This suggests that transplantation of anin vivorituximab-purged autograft is a promising strategy for primary bone marrow DLBCL.

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