scholarly journals Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3787-3794 ◽  
Author(s):  
R Haas ◽  
R Mohle ◽  
S Fruhauf ◽  
H Goldschmidt ◽  
B Witt ◽  
...  
Keyword(s):  
Malignant Lymphoma ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Poor Prognosis ◽  
Collection Efficiency ◽  
Hodgkin’S Disease ◽  
Cytotoxic Chemotherapy ◽  
Large Field ◽  
High Dose ◽  
Cd34 Cells

Abstract 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.

scholarly journals Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3787-3794 ◽  
Author(s):  
R Haas ◽  
R Mohle ◽  
S Fruhauf ◽  
H Goldschmidt ◽  
B Witt ◽  
...  
Keyword(s):  
Malignant Lymphoma ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Poor Prognosis ◽  
Collection Efficiency ◽  
Hodgkin’S Disease ◽  
Cytotoxic Chemotherapy ◽  
Large Field ◽  
High Dose ◽  
Cd34 Cells

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.

scholarly journals Atypical hodgkin and reed-sternberg cells in peripheral blood of a patient with advanced stage of Hodgkin's disease - a case report

2003 ◽  
Vol 131 (9-10) ◽  
pp. 400-402 ◽  
Author(s):  
Rajko Milosevic ◽  
Milica Colovic ◽  
Vesna Cemerikic-Martinovic ◽  
Natasa Colovic ◽  
Marina Bogunovic
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Mononuclear Cells ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
High Dose ◽  
Advanced Stage ◽  
Neck Lymph Nodes

The occurrence of abnormal Hodgkin's and Reed-Sternberg cells in the peripheral blood in a patient suffering from Hodgkin's disease has been noticed exceptionally rare in a previous period, and especially rare in last ten years primarily due to successfull treatment of this disease. The presence of atypical mononuclear cells in peripheral blood which cytomorphologically resembled Reed-Sternberg cells was registered in 8 patients till 1966. During the last decade, the presence of atypical mononuclear cells in the peripheral blood was used for their isolation cultivation, and detailed immunophenotypic and genetic analysis. The analysis of mononuclear cells in rare patients with Hodgkin's disease was established that they belong to the B-lymphoid cells with expression of CD30 and CD15 antigens. The examination of presence of Hodgkin's cells in the peripheral blood of patients with Hodgkin's disease is important for patients with advanced stage of the disease in which autologous stem cell transplantation and high dose chmeotherapy is planned. The authors present a 33-year-old patient, who noticed enlarged neck lymph nodes in September 2000, high temperature and loss in weight. On physical examination enlarged neck lymph nodes 5x8 cm and hepatosplenomegaly were found. There was anemia and thrombo-cytopenia, and normal WBC count with 24% of lymphoid elements in differential formula. On histologic examination of lymph nodes Hodgkin?s disease, type nodular sclerosis with mixed cellularity was found. Histology of bone marrow showed nodal lymphomatous infiltration. Immunohistochemistry with monoclonal antibodies of concentrate of peripheral blood cells showed expression of CD30+ and CD15+, immunophenotypically and morphologically matching Reed-Sternberg cells. Cytogentic analysis of mononuclear cells of the bone marrow showed normal karyotype. The patient was in clinical stage IV/V of the disease and chemotherapy with 9 cycles of ABVD+Mp protocol was applied. He is still in remission.

Superoxide anion (O-2) production by peripheral blood monocytes in Hodgkin's disease and malignant lymphoma.

1985 ◽  
Vol 3 (5) ◽  
pp. 641-645 ◽  
Author(s):  
R Perez-Soler ◽  
G Lopez-Berestein ◽  
F Cabanillas ◽  
P McLaughlin ◽  
E M Hersh
Keyword(s):  
Complete Remission ◽  
Malignant Lymphoma ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Superoxide Anion ◽  
Hodgkin’S Disease ◽  
Delayed Type Hypersensitivity ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Increased Risk

Superoxide anion (O-2) is the first metabolite of the monocyte oxygen burst pathway, which plays an important role in the monocyte microbicidal function. The capacity of peripheral blood monocytes to produce O-2 was studied in 63 patients with Hodgkin's disease (31 with active disease and 32 in complete remission), 15 patients with active malignant lymphoma, and 57 normal control subjects. O-2 release was quantified by evaluating superoxide dismutase-inhibitable reduction of cytochrome c after stimulation of monocytes with phorbol myristate acetate. Results were expressed in nanomols O-2 per mg protein per hour. O-2 production was lower than normal in patients with active Hodgkin's disease (163.3 v 214.5, P less than .05). It was normal in patients with Hodgkin's disease in complete remission (216.2 v 214.5, P greater than .05) and high in patients with malignant lymphomas (317.9 v 214.5, P less than .01). Within the group with active Hodgkin's disease, patients in relapse after therapy had a lower O-2 production than those previously untreated (99.8 v 181.8, P less than .01). Stage of disease was unrelated to the defect. The presence of B symptoms and a decreased delayed type hypersensitivity to recall skin test antigens were associated with normal O-2 production. The results obtained suggest that monocyte dysfunction is part of the immune dysregulation associated with active Hodgkin's disease. The O-2 determination is a relatively easy test to perform and may be useful in identifying the patients with Hodgkin's disease who have an increased risk of opportunistic infections.

A Mobilizing Regimen of AMD3100 and G-CSF Increases Stem Cell Collection in Patients with Hodgkin’s Disease, and PK Is Similar to That of Non-Cancer Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3053-3053 ◽  
Author(s):  
Amanda F. Cashen ◽  
Gary Calandra ◽  
Ron MacFarland ◽  
Sandra Lopez ◽  
John F. DiPersio
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Plasma Concentrations ◽  
Control Group ◽  
Peripheral Blood Stem Cells ◽  
Platelet Recovery ◽  
Cd34 Cells ◽  
Historical Controls

Abstract For patients undergoing autologous peripheral blood stem cell transplantation (PBSCT), the number of CD34+ cells collected is a reliable predictor of neutrophil and platelet engraftment after transplantation, with doses > 5 x 106 CD34+ cells/kg associated with faster count recovery. Unfortunately, collection of an adequate number of peripheral blood stem cells (PBSCs) can be difficult in Hodgkin’s disease (HD) patients. AMD3100 reversibly inhibits the binding of stromal cell-derived factor 1 (SDF-1), constitutively expressed on bone marrow stromal cells, to its receptor CXCR4, expressed on CD34+ cells. AMD3100 combined with G-CSF has been shown to improve PBSC collection compared to mobilization with G-CSF alone in patients with multiple myeloma or non-Hodgkin’s lymphoma (Blood2005;106:1867). This study was undertaken to determine whether a mobilization regimen of AMD3100 + G-CSF can safely and effectively mobilize PBSCs in patients with HD who are undergoing autologous PBSCT. Results were compared to a historical control group comprised of 98 consecutive HD patients who underwent G-CSF-alone mobilization at our institution. Patients were followed post-transplant to evaluate engraftment timing and durability. Pharmacokinetic (PK) determinations were completed in a subset of patients (n=6) following the first dose of AMD3100. To date, 19 patients with relapsed (17) or refractory (2) HD have been mobilized with G-CSF (10 ug/kg/d) + AMD3100 (240 ug/kg/d sc at 10 p.m. beginning on day 4). Apheresis was performed 11 hours after each AMD3100 dose. The first dose of AMD3100 produced a median (range) 3.0 (1.9–12) fold increase in the number of circulating CD34+ cells. Twelve patients (63%) achieved a collection of ≥ 5 x 106 CD34+ cells/kg, a significantly higher proportion than historical controls (15%, p=0.049). Eighteen patients (95%) mobilized with AMD3100 + G-CSF collected > 2 x 106 CD34+ cells/kg (range, 0.9–9.6 x 106 CD34+ cells/kg), compared to 78% of controls (p=0.116). The median (range) number of apheresis procedures performed per patient was 2 (1–5). The median collection in the first two days of pheresis was 5.0 x 106 CD34+ cells/kg, which is significantly better than historical controls, who collected a median 3.0 x 106 CD34+ cells/kg in the first two days of pheresis (p=0.002). No grade II-IV adverse events were ascribed to AMD3100. Eighteen patients were transplanted with G-CSF + AMD3100 mobilized cells. All had prompt and stable engraftment, with median neutrophil recovery at day +9 (8–11) and median platelet recovery at day +15 (9–20). PK studies demonstrated that AMD3100 was rapidly absorbed following subcutanetous injection, with a median (range) Cmax of 0.87 (0.66–1.16) ug/ml. Plasma concentrations declined in a bi-exponential manner, with a median elimination half-life of 3.7 (2.4–4.0) hours. The median AUC0–infinity was 3,749 (2,808–4,761) ug-hr/ml. AMD3100 pharmacokinetics in this patient population are consistent with results previously obtained from healthy volunteers in the absence of G-CSF. We conclude that AMD3100 + G-CSF is a well-tolerated and effective mobilization regimen in patients with HD. For these patients, AMD3100 + G-CSF can improve the number of PBSCs collected and decrease the number of days of pheresis.

scholarly journals An Evaluation of Paraffin Sections of Aspirated Bone Marrow in Malignant Lymphomas

Blood ◽  
1955 ◽  
Vol 10 (8) ◽  
pp. 820-830 ◽  
Author(s):  
JACQUELINE D. PETTET ◽  
GERTRUDE L. PEASE ◽  
TALBERT COOPER
Keyword(s):  
Bone Marrow ◽  
Malignant Lymphoma ◽  
Peripheral Blood ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Reticulum Cell ◽  
Reticulum Cell Sarcoma ◽  
Paraffin Sections ◽  
Malignant Lymphomas ◽  
Cell Sarcoma

Abstract Examination of serial paraffin sections of bone-marrow aspirations has increased the known incidence of marrow involvement in malignant lymphomas. The results of this study can be seen in the table. In the 72 cases reviewed here, lesions compatible with malignant lymphoma were seen in paraffin sections in 22 cases. In 12 cases this was the only material available for diagnosis at the time. In an additional seven cases paraffin sections were considered suggestive of malignant lymphoma and in five of these a diagnosis could be made on the basis of examination of both smear and paraffin section. This procedure is particularly helpful in Hodgkin’s disease and reticulum cell sarcoma, where marrow smears are only rarely diagnostic. In general, the patients in whom lesions were found in the bone marrow tended to have more advanced disease than those in whom lesions were not found, and abnormalities in the peripheral blood were more common. This was especially true of patients with Hodgkin’s disease, less so in those with reticulum cell sarcoma. Patients with lymphosarcoma, lymphocytic type, did not show this difference, either in the extent of the disease or in findings on examination of peripheral blood. Diagnosis was most difficult in patients who had lymphocytic lymphosarcoma, since it was occasionally difficult to distinguish between the benign aggregations of lymphocytes which are not infrequently found in a large number of unrelated conditions and those aggregations which represented malignancy. Differentiation was made on the basis of number of aggregations, degree of circumscription, presence or absence of reaction centers and the cytologic appearance of the cells. Examination of the smears of the marrow is most helpful in these cases. Seven patients in this series (9.7 per cent) had granulomatous lesions in the marrow. In five of these the final diagnosis was Hodgkin’s disease, in one reticulum cell sarcoma and in one follicular lymphoma. Although these lesions were not specific, the incidence is high enough to make the finding of a granuloma of some significance in any patient suspected of having malignant lymphoma. The importance of thorough examination of any material obtained in an apparent dry tap and the value of repeated marrow-examinations is emphasized by three cases in this series. Since in many cases diagnostic lesions are found in only one portion of the material, examination of only one section of the paraffin sections of aspirated bone marrow is not sufficient for proper evaluation. This fact is emphasized by the greater incidence of positive findings in this report than in that of Cooper and Watkins. Studies of bone marrow should be particularly helpful in instances in which the diagnosis of malignant lymphoma is suggested by clinical features but cannot be proved by biopsy of peripheral nodes or other readily accessible tissue.

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