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J Stachowiak

Publications and source records attributed to J Stachowiak.

At least 37 records · Page 2Linked to original sources
PubMed1985

Autologous bone marrow transplantation with marrow decontaminated by immunotoxin T 101 in the treatment of leukemia and lymphoma: first clinical observations.

Four patients with T-cell malignancies of poor prognosis (three with non-Hodgkin's lymphoma and one with acute lymphoblastic leukemia) received the following consolidation therapy for complete or partial remission: cyclophosphamide (120 mg/kg) plus total-body irradiation, followed by reinfusion of cryopreserved autologous marrow previously purged in vitro by immunotoxin T 101 (SR 41322). This immunotoxin is made of the murine monoclonal T 101 antibody coupled to chain A of ricin. The doses of immunotoxin used were 10(-9) and 10(-8) M, and the durations of incubation were 4 and 20 hours at 37 degrees C. Recovery of progenitors CFUc and BFUe was total following incubation with immunotoxin T 101, but diminished after cryopreservation (15%-80% for CFUc, 33%-47% for BFUe), suggesting an increased fragility of the incubated progenitors to freezing. In every case, hematopoietic recovery occurred within normal time periods, with a wbc count greater than 10(9)/L and a platelet count greater than 50 X 10(9)/L on Day 22 (range, 15-31) and Day 21 (range, 22-47), respectively, demonstrating the feasibility of autologous bone marrow transplantation with marrow pretreated by immunotoxin. However, the slow recovery of lymphocytes and the development of severe infections in two patients may indicate that an in-depth study of immunological reconstitution after in vitro treatment of the marrow with immunotoxin T 101 is necessary.

Adolescent↗
PubMed1984

Autologous bone marrow transplantation in the treatment of poor prognosis non-Hodgkin's lymphomas.

Twelve patients with non-Hodgkin's lymphomas of poor prognosis were treated by TACC high-dose chemotherapy (cyclophosphamide 45 mg/kg/day X 4, cytosine arabinoside 200 mg/m2 i.v. q 12 hr X 7,6-thioguanin 100 mg/m2 p.o. X 7 and CCNU 200 or 250 mg/m2 p.o., single dose) followed by autologous bone marrow transplantation (ABMI) (infused dose: 853-20,000 CFU-c/kg). Patients were divided into 2 groups: those in primary therapy with high tumor load (group 1; 3 initial diagnoses, 3 relapses) and those in consolidation therapy for a low tumor load (group 2; 5 complete and 1 partial remissions). Results show that: (1) the aplasia following autologous bone marrow transplantation was short. Leukocyte (greater than 10(9)/1) and platelet (greater than 50 X 10(9)/1) recoveries were observed on day 12 (range, 9-19) and day 14 (range, 8-27). (2) In group 1 there were 3 complete remissions (8,21, 45+ months) and 3 failures, including 1 death to toxicity of TACC. The 3 remissions occurred in patients in primary therapy and overall survival of these patients from the time of initial diagnosis was 48+, 48+ and 60+ months. In group 2 there were 5 persisting complete remissions (12+ to 40+ months) and 1 failure. Overall survival of these patients was 23+, 24+, 27+, 42+ and 70+ months. In both groups failures were associated with contamination of the frozen marrow by tumor. The toxicity of the association TACC + ABMT was acceptable and dominated by the risk of pericardial effusion and infection. The latter was absent in group 2 and occurred in 5/6 cases in group 1. These preliminary results indicate that autologous bone marrow transplantation has a possible role in the aggressive treatment of non-Hodgkin's lymphomas of high-grade malignancy and that its use should preferentially be in the consolidation mode.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

[Non-Hodgkin's malignant lymphoma. Therapeutic value of autologous bone marrow transplantation].

Twelve patients with non-Hodgkin malignant lymphoma of poor prognosis were treated with heavy chemotherapy of the TACC type (cyclophosphamide 45 mg/kg/day i.v. X 4; cytosine arabinoside 200 mg/m2/12 hours i.v. X 7; 6-thioguanidine 100 mg/m2/12-hourly p.o X 7 and CCNU 200 or 250 mg/m2 p.o. single dose) followed by autologus bone marrow transplantation (853 to 20.000 CFUc/kg). The patients were divided into 2 groups depending on whether they received an induction treatment for large visible tumoral mass (group I: 3 initial presentations, 3 relapses) or a consolidation treatment for small residual tumour (group II: 6 complete and 1 partial remissions). The results show that autologous bone marrow transplantation shortens the duration of the therapeutic aplasia. White cell (greater than 10(9)/l) and platelet (greater than 50.10(9)/l) recovery was observed on days 12 (range 9-19) and 14 (range 8-27) respectively. In group I, 1 patient died of myocardial TACC toxity and acute renal failure on tumoral kidney; there were 2 failures and 3 complete remissions (8, 21, 45 + months). Remissions occurred in patients treated initially; the overall survival since diagnosis was 48+, 48+ and 60+ months. In group II patients there were 1 failure and 5 complete remissions persisting after a 2+ months to 30+ months follow-up; the overall survival was 23+, 24+, 27+, 42+ and 70+ months. The 3 failures in the series occurred in circumstances suggesting contamination of the cryopreserved bone marrow by tumoral cells. The toxicity, largely due to infection, of the TACC-bone marrow transplantation combination was tolerable. It was clearly lower in group II (6 patients, no septicaemia) than in group I (5/6 patients with septicaemia). These preliminary results confirm that there is room for autologous bone marrow transplantation in highly malignant non-Hodgkin lymphomas, particularly during complete remissions to facilitate the use of an aggressive consolidation chemotherapy.

Adult↗
PubMed1983

Delayed kinetics of recovery of haemopoiesis following autologous bone marrow transplantation. The role of excessively rapid marrow freezing rates after the release of fusion heat.

Thirty-five patients were treated by intensive chemotherapy and/or whole-body irradiation followed by reinjection of cryopreserved autologous bone marrow. In 8 patients the kinetics of recovery of haemopoiesis was delayed (recovery to 10(9) leucocytes/litre beyond day 27 and recovery to 50 X 10(9) platelets/litre beyond day 25). This delay was directly responsible for the death of 3 patients and contributed to a fatal outcome in 2 others (mortality rate 9-14%). Retrospective analysis of these 8 cases revealed that failure of autologous transplantation was associated with poor recovery of CFUc, which was in turn related to an excessively rapid freezing rate after the release of fusion heat. Recovery of CFUc to 50% or more was achieved in 100% of cases when the freezing rate was less than 5 degrees C/min, 45% for freezing rates between 5 and 10 degrees C/min and 22% when the freezing rate exceeded 10 degrees C/min (n = 71, P less than 0.001). There was an inverse linear or logarithmic relationship between CFUc recovery and freezing rate after the transition phase (r = -0.46, r = -0.43, P less than 0.001). The quantity of nitrogen introduced into the freezing chamber to annul the fusion heat must therefore be calibrated with accuracy so that the desired shortening of the transition phase will not be accompanied by an overly marked increase in the freezing rate, which would result in the destruction of stem cells. To ensure an adequate freezing rate, it is crucial to monitor the temperature continuously in each sample of bone marrow during the freezing process. This study also suggested that other factors may have interfered with the kinetics of recovery after autologous bone-marrow transplantation. These factors include myelofibrosis, the presence of an Australia antigen and administration of compounds that are toxic for the bone marrow after reinjection of cryopreserved marrow. However, the responsibility of these factors cannot be stated with certainty.

Adult↗
PubMed1982

[Management of polycythaemia with pipobroman].

From 1971 to 1980, 86 patients with polycythaemia (vera 69, undetermined 15 and respiratory 2) were treated with pipobroman (N,N' bis bromopropionyl piperazine). The initial treatment in doses of 75 mg/day resulted, within 45 days, in complete remission in 46/49 new patients (93.9%), and in 17/20 previously treated patients with polycythaemia vera (85%) and in 14/15 patients with apparently primary polycythaemia. The main duration of the first remission was 17.5 months. Relapses occurred in 30% of the cases but responded to pipobroman at the initial high dosage level. Low-dose maintenance treatment appears to be necessary. Adverse effects on the blood were rare; they included leucopenia (8%) and moderate thrombocytopenia (7%); macrocytosis was noted in 20% of the patients. Acute leukaemia (3 cases) and osteomyelofibrosis (3 cases) were only observed in patients previously treated with 32 P or busulfan. Pipobroman therefore appears to be much less toxic than other alkylating agents. Its is as effective as 32 P but acts more rapidly. It seems to have little oncogenic power, but a more prolonged study is required to ascertain this point.

Female↗
PubMed1982

Combination chemotherapy with cyclophosphamide, vincristine, prednisone and the contribution of adriamycin in the treatment of adult non-Hodgkin's lymphomas a report of 131 cases.

Between January 1973 and January 1979, 131 patients with malignant non-Hodgkin's lymphomas (107 lymphocytic lymphomas, 24 histiocytic lymphomas) were treated with cyclophosphamide-vincristin-prednisone (CVP) either alone or combined with Adriamycin (CVP-A). Stage I and II lymphocytic lymphomas were all treated by CVP combined with radiotherapy. The survival curve for this group of patients plateaued at 89% from the 12th to the 60th month, which was the endpoint of the study. For Stage III and IV nodular lymphocytic lymphomas, actuarial survival was 69% at five years in the CVP-treated group as compared to 54% at three years in the group treated with CVP-A. For Stage III and IV diffuse lymphocytic lymphomas, the complete response rate and median survival were respectively 25% and 24 months in patients treated with CVP, as compared to 67% (P less than 0.01) and 26 months in the group treated with CVP-A. For histiocytic lymphomas, the complete response rate was 50% in the CVP-treated group as compared to 83% in the group treated with CVP-A. Most remarkable was the fact that while in the CVP treated group median survival was only 17 months, the small group of patients treated with CVP-A exhibited considerably improved survival with a horizontal survival curve at 90% after 36 months (12 patients). These results show that the CVP protocol remains an excellent treatment for nodular lymphocytic lymphomas. The addition of Adriamycin (CVP-A) as well as its inclusion in other drugs combination, has raised hopes for remissions of long duration and even for cures in patients with histiocytic lymphomas. Finally, in diffuse lymphocytic lymphomas, efforts will have to be pursued to improve the prognosis which remains poor despite the increased complete response rate achieved by the addition of Adriamycin.

Adolescent↗
PubMed1982

[Bone marrow repopulation after heavy chemotherapy and autologous bone marrow transplantation. Monitoring with biopsies and marrow culture on agar (author's transl)].

Repopulation of the bone marrow after heavy chemotherapy and autologous transplantation was monitored by means of biopsies and bone marrow cultures on agar carried out simultaneously from the 2nd to the 33rd days after transplantation. A parallelism was observed between the reappearance of cell clusters on biopsy material and the growth of colonies in cultures, both being the centres from which the corresponding series proliferated. The clusters were almost invariably formed of one series. Repopulation began 3 to 5 days after transplantation and was complete between the 10th and 20th days. Oedematous dissociation persisted long after the clusters reappeared. Bone marrow repair was virtually always accompanied by plasmocytosis.

Adolescent↗
PubMed1982

Pipobroman therapy of polycythemia vera.

Between 1971 and 1981, 74 patients with polycythemia vera were treated with pipobroman using a high-dose induction, low-dose maintenance regimen. Complete remission was achieved in 51 of 54 previously untreated patients (94.4%) and in 17 of 20 patients (85%) previously treated wih radioactive phosphorus (32 p) and busulfan. The earliest modifications were noted on day 16, and on the average, blood counts were normal by day 45. Thirty percent of the patients relapsed, the mean duration of the remission being 17.5 mo. Following recurrence pipobroman was consistently effective in the same doses but the mean duration of the next remissions was 10 mo. Transient leukopenia and thrombocytopenia occurred in 8% and 7% of patients, respectively, during initial phase, and anemia was noted in 3 patients. Macrocytosis was noted in 20% of patients during maintenance phase. Three cases of acute leukemia and 3 cases of osteomyelosclerosis were recorded, all occurring in patients who had previously received 32 p and/or busulfan. No hematologic malignancies were seen among patients treated with pipobroman alone; follow-up exceeded 6 yr for 20 patients and the median follow-up period was 3.6 yr. Pipobroman appears safer than other alkylating agents; it is as effective as 32 p and works more quickly. Longer follow-up will be required to evaluate the drug's oncogenic potential, which is still not known.

Drug Evaluation↗
PubMed1982

Study of granulocyte-macrophage progenitor (CFUc) preservation after slow freezing of bone marrow in the gas phase of liquid nitrogen.

Storage of human hematopoietic stem cells has been made possible through effective preservation of viability by freezing technique. We have studied the quantitative and qualitative aspects of granulocyte-macrophage precursor (CFUc) recovery from 29 bags of frozen bone marrow stored at - 160 degree C in the gas phase of liquid nitrogen for several months or years. it has been shown that with the freezing and preservation technique used, over 75% of the proliferative capacity of the cryopreserved CFUc was recovered. The influence of various factors on the quality of bone marrow preservation was studied and showed that dimethylsulfoxide (DMSO) appeared to cause substantial loss of CFUc at 4 degree C. Evaluation of CFUc in vitro is essential for determining the quality and richness of cryopreserved bone marrow with a view to using such marrow for autologous grafting intensive chemotherapy or total body irradiation in patients with hematological malignancies or solid tumors. No correlation was found between the number of nucleated bone marrow cells and CFUc content.

Adolescent↗
PubMed1981

[Acute leukaemias with myelofibrosis. Clinical, cytohistological and evolutive aspects. Their place among malignant blood diseases with myelofibrosis (author's transl)].

In a series of 154 patients with acute leukaemia (AL), 31 had myelofibrosis. The authors report in detail on 9 of these and demonstrate the distinctive features of this form of AL: pancytopenia is severe, circulating blast cells are rare, myelograms are difficult to read, and bone-marrow biopsies are necessary to the diagnosis, severity assessment and prognosis of the disease. Owing to the small number of cells, it is uneasy to distinguish these AL from acute myelofibrosis (a nosological entity which needs to be more precisely defined) and from megakaryoblastic leukaemias, recently individualized.

Acute Disease↗
PubMed1980

[Studies of immunological status, following autologous bone marrow transplantation in man (author's transl)].

Following transplant, circulating immunoglobulin levels fell moderately and remained depressed less than 2 months for IgG, and for variable and longer periods of time for IgM and IgA. Repeated quantitative determinations of antibodies against multiple antigens did not show any decrease in the pretransplant levels. Indeed some patients developed herpes and cytomegalovirus infections to which they responded by a sharp increase in antibody titers. In 2 cases, a primary immunization was demonstrated (against CMV and BK virus) with increasing levels of IgM and IgG antibodies. Lymphocyte counts in peripheral blood returned to 500 mm# between day 10 and 29 (median day 18) and to pretransplant values within 6 weeks. Non specific stimulation of lymphocytes by mitogens in the immediate post-transplant period showed a decreased response to PHA and Con A, whereas the responses to pokeweek mitogens and alloantigens were only slightly diminished. The degree of the responses was related to the dose of cryopreserved marrow infused. We conclude that:--although the minimum dose for autologous bone marrow transplantation in man is around 0,5 10(8) nucleated bone marrow cells/Kg, much higher doses should be used to ensure faster and better restoration of immune reactivity.--The similarity of the immunological dysfunction following autologous and allogeneous bone marrow transplantation suggest that, in the immediate post-transplant period, the role of GVHD in cellular immunity depression may be minimal.

Bone Marrow Transplantation↗
PubMed1979

[Massive medullary forms of Hodgkin's disease and acute myelofibrosis (author's transl)].

Ten cases of Hodgkin's disease was massive bone marrow invasion. This particular form of the disease is seen either at the outset or in Stage IIIB with a rapid course. It is reflected by a pancytopaenia with poor marrow with little or no superficial nodes. These very atypical forms of Hodgkin's disease must thus always be considered as a possibility in the context of acute malignant myelofibrosis. They indicate a special and unexplained behaviour of the host to the Hodgkin's tumour.

Acute Disease↗
PubMed1978

Lymphomas of the spleen and bone marrow lymphoid nodules.

Many nodular primitive non-Hodgkin's lymphomas of the spleen have a favourable course after splenectomy or chemotherapy. Several observations of this type have been reported in the literature, in which the concept of malignancy is discussed, authors referring to a presarcomatous state or to an idiopathic splenomegaly. The evaluation of the extension of those sarcomas, however, very often show hepatic lesions, and always an increase in the lymphoid marrow nodules. The significance of these nodules is discussed here, with reference to 14 personal observations. These nodules may not always reflect a real extension of the sarcoma to the marrow. From a practical point of view, the presence of lymphoid marrow nodules, when associated with an isolated splenomegaly, is a strong argument to suspect a sarcoma of the spleen, and indicates a splenectomy.

Adult↗