Progressive renal failure in two breast cancer patients after high-dose ifosfamide.
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Biomedical subjects
Publications and source records attributed to H Goldschmidt.
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For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.
The introduction of new surgical techniques and other therapeutic modalities has markedly influenced the use of ionizing radiation therapy in dermatology. X-rays and electron beams are now used only for a limited number of indications in carefully selected patients. Since surgical approaches have gained popularity in the treatment of skin tumors, not all dermatologists are familiar with the benefits of ionizing radiation for patients with cutaneous neoplasms and certain other skin disorders. This article reviews modern indications for radiation therapy in dermatology. Important physical and biologic factors, radiation side effects, radiation protection measures, and therapeutic results will also be discussed. Although the use of radiotherapy in dermatology has in large part been supplanted in recent years by other forms of treatment, ionizing radiation continues to be an essential therapeutic alternative for many cutaneous tumors and some skin diseases. It is important to be familiar with the principles of radiotherapy so that optimal therapy can be selected for individual patients.
The purpose of this study was to evaluate the antigenic profile of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and multiple myeloma (MM). The mobilization regimens consisted of high-dose cytarabine/mitoxantrone for patients with NHL, DexaBEAM for patients with HD, and high-dose cyclophosphamide (4 or 7 g per m2) for patients with MM. Cytotoxic therapy was supported by recombinant human G-CSF (Filgrastim, 300 micrograms/day sc) to shorten the period of neutropenia and to increase the number of circulating hematopoietic progenitor cells. The mean numbers of circulating CD34+ cells/microliters during leukocyte recovery were different between patient groups, 80.5 +/- 9.8 (mean +/- SEM) in low-grade NHL and 51.2 +/- 9.7 in high-grade NHL compared with 31.3 +/- 6.9 in HD and 24.4 +/- 4.1 in patients with MM. As a result, the greatest numbers of CD34+ cells/kg collected per leukapheresis were observed in patients with NHL, whereas the collection efficiency was substantially lower in patients with HD or MM. Patients with MM had also the smallest proportion of CD34+ cells in the mononuclear cell fraction (mean 0.79 +/- 0.10% versus 2.15 +/- 0.19% in low-grade NHL) but the greatest proportion of early CD34+ HLA-DR- progenitor cells (mean 2.38 +/- 0.51 versus 0.84 +/- 14% in low-grade NHL). Patients with MM had a mean proportion of CD34/c-kit+ cells that was twofold greater than that observed in patients with high- or low-grade NHL.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: To evaluate the feasibility of a sequential high-dose therapy with peripheral-blood progenitor-cell (PBPC) support in patients with follicular lymphoma. PATIENTS AND METHODS: Since July 1991, we have included 30 patients (17 men and 13 women) with a median age of 41 years (range, 26 to 55) in the study. At the time of study entry, 17 patients were in first and six in second or higher remission. Another six patients had relapse of disease and one had tumor progression. PBPC were collected during filgrastim-supported leukocyte recovery following high-dose cytarabine (ara-C)/mitoxantrone (HAM). RESULTS: A median of two leukaphereses (range, one to seven) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 2.9 to 23.7 x 10(6). A distinct population of B-lymphoid progenitors (CD34+/CD19+) was not detectable in the autografts, and the content of CD19+ B cells was remarkably low, comprising a median of 0.07% of the mononuclear cells. Using the polymerase chain reaction (PCR) assay for the major breakpoint regions (MBR) of the bcl-2/immunoglobulin H (IgH) translocation, 22 patients had autografts positive for the t(14;18) translocation, whereas seven patients had PCR-negative transplants. The autograft of one patient could not be assessed. Following myeloablative therapy, hematologic recovery was rapid without cytokine support. The median times to reach a platelet count > or = 20 x 10(9)/L and neutrophil count > or = 0.5 x 10(9)/L were 11 and 13 days, respectively. Nonhematologic toxicity was moderate. Twenty-nine patients were alive in remission after a median follow-up duration of 6 months (range, 1 to 18). Of 22 patients autografted with t(14;18)-positive harvests, 11 had PCR-detectable cells in bone marrow and/or peripheral blood as long as 16 months posttransplantation. In contrast, six patients became PCR-negative between 3 and 16 months after reinfusion. Follow-up examinations with PCR data for the remaining five patients are not yet available. CONCLUSION: Conversion to PCR negativity in patients autografted with PCR-positive harvests suggests that the myeloablative regimen is effective and that any reinfused t(14;18)-positive cells may not be sustained. Because conventional chemotherapy provides no cure, we believe that high-dose therapy including total-body irradiation (TBI) should be explored in these particularly radiosensitive lymphomas.
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PURPOSE: In combined modality treatment of early stage, high grade non-Hodgkin's lymphoma disease status after initial chemotherapy was analyzed to evaluate the impact of remission status on survival. Analysis of relapse patterns was performed to assess efficacy of radiation doses and volume. PATIENTS AND METHODS: Fifty-four patients with early stage high grade non-Hodgkin's lymphoma were treated with radiotherapy alone or with initial chemotherapy followed by involved field irradiation. Overall survival, relapse-free survival and relapse patterns were analyzed. RESULTS: In patients treated with radiotherapy alone (stage I n = 15, stage II n = 8) overall survival rate was 69%, relapse-free survival was 35% at 3 years. Patients achieving combined modality treatment (stage I n = 5, stage II n = 26) showed an actuarial 3 year overall survival of 78%, relapse-free survival was 62%. Complete remission status after chemotherapy was an important factor for durable disease control. Those patients, who achieved complete remission after chemotherapy showed an actuarial relapse-free survival of 75% at 3 years. Patients with partial remission or progressive disease after chemotherapy had a poor outcome (relapse-free survival 35%). Analysis of the first manifestation of lymphoma progression after radiotherapy in relation to the treatment portals demonstrated radiotherapy to be highly effective in achieving local control. Only 8% of recurrences occurred within the irradiated volume. 56% of failures were found in non-contiguous sites to the former radiation portals. CONCLUSION: This analysis suggests that effective chemotherapy in combination with involved field radiotherapy in CS I (with risk factors) and especially in CS II patients is necessary to control extension of non-Hodgkin's lymphoma.
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Hematopoietic growth factors can be used for the mobilization of peripheral blood stem cells that have the proliferative capacity to restore long-term hematopoiesis after myeloablative therapy. An association between specific cytokines and the composition of the blood-derived progenitor cells has not yet emerged. It appears that yield and composition of PBSC are influenced far more by the individual than by the use of specific growth factors. Our future studies will focus on how many and what kind of stem cells are needed for high-dose regimens with different myelotoxicity. In parallel, autografts will be assessed for contaminating tumor cells, if disease- or clone-specific markers are available. This approach may then provide the rationale for the increasing use of PBSC for autografting.
This report summarizes our results of sequential treatment with IL-3 and GM-CSF following high-dose chemotherapy with respect to the yield and composition of peripheral blood stem cells (PBSC). Eight patients with high-grade non-Hodgkin's lymphoma were included in the study. Starting 24 h after high-dose cytosine arabinoside (Ara C)/mitoxantrone, IL-3 was given for 6 days, followed by GM-CSF. The increase of circulating hematopoietic progenitor cells during leukocyte recovery varied substantially from patient to patient. Up to a 22-fold interindividual difference was observed for the peak levels of CD34+ cells. A special focus of our study was the antigenic profile of the CD34+ PBSC. On analysis of the antigenic profile of the CD34+ cells, the proportion of CD34+/HLA-DR- and CD34+/CD38- cells representing non-committed hematopoietic stem cells was consistently < 5%. The vast majority of CD34+ cells was found to coexpress CD33 (86.3 +/- 2.1%, mean +/- SEM), reflecting myeloid lineage commitment. CD71 antigen was present on 47.4 +/- 3.0% CD34+ cells with two populations (CD71dim/bright), while the percentage of early B lymphoid (CD34+/CD19+) progenitor cells was extremely low (0.38 +/- 0.13%). We therefore conclude that the cytokines currently available such as G-CSF, GM-CSF or IL-3 facilitate an ontogenetic phenomenon supporting the redistribution of hematopoietic progenitor cells after cytotoxic treatment. Six patients were autografted with the IL-3/GM-CSF-exposed blood stem cells following high-dose conditioning therapy. It is worth noting that no additional BM or hematopoietic growth factors were given post-transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
High-dose conditioning therapy followed by autografting with blood stem cells rather than bone marrow has become an increasingly used transplantation modality for patients with chemosensitive malignancies. We treated 10 patients with malignant lymphoma in sensitive relapse with recombinant human granulocyte colony-stimulating factor (rhG-CSF) following salvage therapy. rhG-CSF was given subcutaneously (5 micrograms/kg/day) starting 24 hours after chemotherapy and stem cell collection was performed by repeated leukaphereses during leukocyte recovery. The yield of myeloid progenitors varied between 0.79 and 38.36 x 10(4) CFU-GM/kg body weight (median 4.1 x 10(4). A strong correlation was found between the number of granulocyte-macrophage colony-forming cells (CFU-GM) plus blast-forming erythroid cells (BFU-E) and CD34-positive (CD34+) cells (R = 0.80; p < 0.001). The majority of CD34+ cells (> 95%) strongly coexpressed human lymphocyte antigen-DR (HLA-DR) and CD38, whereas CD33 varied between 20% and 94%. Costaining of CD34+ cells for CD19 above the control level could not be detected, suggesting that early B lymphoid progenitors are not expanded or released into the circulation by rhG-CSF. Following total body irradiation (TBI)/cyclophosphamide or the CBV regimen (cyclophosphamide, BCNU, VP-16), all patients achieved complete engraftment with a median of 14 days for 1.0 x 10(9)/L white blood cells (WBC), 15 days for 0.5 x 10(9)/L polymorphonuclear cells (PMN) and 22 days for 20 x 10(9)/L platelets. The quantity of CFU-GM/kg transplanted was predictive for neutrophil and platelet recovery. The strongest correlation, however, was found between the number of CD34+ cells/kg autografted and platelet recovery (R = -0.86; p < 0.001). The patients transplanted with more than 5 x 10(6)/kg CD34+ cells reached an unsubstituted platelet count > 20 x 10(9)/L within 8 to 12 days. Our data demonstrate that rapid and complete engraftment can be achieved following myeloablative conditioning therapy with rhG-CSF-exposed blood stem cells without the need for additional bone marrow support or growth factor administration posttransplantation.
Thirty-seven patients with Hodgkin's disease in sensitive relapse were autografted using blood-derived haematopoietic progenitor cells. At the time of transplantation 22 patients were in complete remission and 15 patients in partial remission. Twenty-six patients were male and 11 female, with a median age of 31 years (range 21-52). The pre-transplant conditioning therapy consisted of cyclophosphamide, BCNU and etoposide (CBV). Five patients died of transplant-related complications and 11 patients relapsed after a median time of four months following autografting. For the remaining 21 patients the probability of event-free survival (EFS) was 45% at 68 months. Blood progenitor cell collection can be integrated into salvage therapy by administering haematopoietic growth factors (HGFs) to enhance the chemotherapy-induced progenitor cell rebound during leucocyte recovery. In a subgroup of 14 patients, seven received recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (250 micrograms/m2/day) by continuous intravenous infusion following dexamethasone, BCNU, etoposide and melphalan (Dexa-BEAM) as salvage therapy, while seven patients were treated without haematopoietic growth factor (HGF) post-chemotherapy. The yield of total nucleated cells (TNC) and granulocyte-macrophage colonies (CFU-GM) collected per leukapheresis was 2.2- and 2.4-fold higher respectively in the rhGM-CSF-treated patients. Following high-dose conditioning therapy, the seven patients autografted with rhGM-CSF-mobilised stem cells showed a faster leucocyte recovery compared with the control group. Neutrophil recovery (> 1.0 x 10(9)/L) and platelet recovery (> 20 x 10(9)/L) were also accelerated in the rhGM-CSF-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND AND DESIGN: Giant aggressive keratoacanthoma is a rare destructive subset of keratoacanthoma that frequently involves the facial region, grows rapidly to a large size, and often recurs after surgical management. The effectiveness of ionizing radiation therapy was examined in a retrospective study involving 16 patients; 14 of the tumors had recurred after surgical therapy. RESULTS: All tumors resolved with satisfactory cosmetic results and without recurrence following a fractionated course of superficial radiation therapy. CONCLUSIONS: Radiation therapy is an effective therapeutic modality for giant aggressive keratoacanthomas.
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The serum concentrations of Ara-C are in the range from 10(-6) to 10(-8) M in LD-Ara-C treated patients. The growth of CFU-GM from bone marrow of healthy volunteers was depressed depending on Ara-C-concentration applied in vitro. The growth of CFU-L from peripheral blood of two patients with AML (M 2) and one patient with CML in blast crisis was differently influenced by Ara-C-application in vitro. An elevated proportion of mature cells was observed in smears of cultured cells with Ara-C from two patients. The usefulness of Ara-C for a differentiation inducing therapy is discussed.