Two autologous transplants in the treatment of patients with Hodgkin's lymphoma: analysis of prognostic factors and comparison with a single procedure.

We summarized registry data of the long term observation of 35 patients treated with two autologous transplants. Prognostic factors for overall survival (OS) and DFS were analyzed. The OS was compared with 105 patients from a single transplant group. Two factors were significant in univariate analysis of DFS after the second transplant: response to the first transplant (complete remission (CR) versus progressive disease (PD) p = 0.041) and the disease status at the time of the second autologous stem cell transplantation (ASCT) (CR versus partial remission (PR) p = 0.004; CR versus PD p = 0.0002). In the multivariate analysis only the last of the parameters remain significant (RR 2.30, p = 0.004, 95% CI; 1.30 - 4.04). In the analysis of OS, two factors were significant in univariate analysis: status of the disease at the first transplant (PR versus PD p = 0.008) and response to the first transplant (CR versus PD p = 0.025). None of those factors remained significant in a multivariate analysis. A probability of 5-year survival after the first transplant in patients treated with two transplants was 83% (95% CI; 70 - 97%). A tendency towards better survival was seen in patients treated with two transplants (p = 0.01). The trend toward better survival from the time of diagnosis is kept for those who entered CR or PR after standard chemotherapy (p = 0.097) but not for the whole group (p = 0.13).

Addition of cladribine to induction/consolidation regimen does not impair peripheral blood stem cell mobilization and bone marrow harvest for autotransplantation in acute myeloid leukemia patients.

BACKGROUND: The previous study by the Polish Adult Leukemia Group has demonstrated that addition of cladribine to standard DNR+AraC induction potentiates the antileukemic activity. The goal of this study was to compare the efficacy of bone marrow or peripheral blood hematopoietic cell collection in patients who obtained remission after daunorubicine plus cytarabine induction with cladribine (DAC-7) or without addition of cladribine (DA-7) in preparation for autotransplantation. PATIENTS AND METHODS: Sixty-six patients aged 41 years (range, 17-58 years) were included in this study: 33 cases in the DAC-7 and 33 in the DA-7 arm. Hematopoietic cells were collected from the bone marrow (ABMT, n = 29) or from the peripheral blood (ABCT, n = 37) using cytopheresis after administration of AraC (2 x 2 g/m2) on days 1, 3, 5 and subsequent G-CSF (10 microg/kg) from day 7 as mobilization therapy. RESULTS: The numbers of harvested CD34+ cells were similar in the DAC-7 and DA-7 pretreated patients both after harvesting from peripheral blood (2.55 x 10(6)/kg vs 2.5 x 10(6)/kg) and from bone marrow (1.62 x 10(6)/kg vs 1.55 x 10(6)/kg), respectively. The proportion of patients with sufficient material for autologous bone marrow transplantation was higher in the DAC-7 compared with the DA-7 arm. All patients engrafted; hematopoietic recovery was similar in both subgroups. CONCLUSION: Addition of cladribine to a standard DA induction does not impair the harvesting of hematopoietic cells and their engraftment after autotransplantation.

Outcome and prognostic factors in advanced Hodgkin's disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients.

BACKGROUND: The reported probability of survival of patients with Hodgkin's disease (HD) following high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) is 35-65% at 5 years. The Polish Lymphoma Research Group investigated retrospectively prognostic factors for overall survival (OS) and event-free survival (EFS), and the risk of secondary malignancies in a large series of patients who underwent HDC/ASCT. PATIENTS AND METHODS: The data of 341 consecutive patients treated in 10 centers from 1990 to 2002 were collected and analyzed. RESULTS: The actuarial 5-year OS and EFS were 64% [95% confidence interval (CI) 57% to 71%] and 45% (95% CI 39% to 51%), respectively. In the multivariate model, unfavorable prognostic factors for EFS were less than partial response at the time of ASCT [relative risk (RR), 2.92 (95% CI 1.68-5.08); P<0.001] and three or more previous chemotherapy lines (RR, 2.16; 95% CI 1.42-3.30; P<0.001). These two factors were also associated with unfavorable OS (RR, 3.32; 95% CI 1.90-5.79; P<0.001 and RR, 2.34, 95% CI 1.51-3.64; P<0.001). Five-year cumulative risk of secondary malignancy was 8.4% (95% CI 2% to 13%) and the only identified risk factor was splenectomy (P=0.02). CONCLUSIONS: HDC/ASCT should be considered early in the course of disease for patients with a response after standard therapy.

Treatment for primary refractory Hodgkin's disease: a comparison of high-dose chemotherapy followed by ASCT with conventional therapy.

Our previously published study showed promising results of autologous stem cell transplantation (ASCT) in patients with primary resistant Hodgkin's disease (HD). Probabilities of overall survival (OS) and progression-free survival (PFS) at 3 years were 55 and 36%, respectively. The present study was undertaken to compare these results with conventionally treated patients and thus evaluate therapeutic options. Retrospective data on 76 adult patients who underwent ASCT were matched with 76 conventionally treated patients from 17 centers. Comparison of clinical characteristics in both groups showed that ASCT patients were younger (24 vs 31.5 years, P=0.001), more frequently presented with 'B' symptoms (P=0.03) and that more patients treated with chemotherapy (CT) had elevated LDH (P=0.03). In univariate analyses, bulky disease (P=0.0043) and complete resistance to standard CT (P=0.051) were found to be risk factors for OS. In a multivariate survival analysis only bulky disease was found to an independent prognostic factor (P=0.005). There was no difference in survival between the treatment groups with 5 years OS 33.7 (CI: 23-46) in the ASCT group and 35.6% (CI: 25-50) for the CT group (P=0.92). We conclude that ASCT is not superior to standard CT for treatment of patients with primary refractory HD.

High-dose chemotherapy with autologous stem cell transplantation is an effective treatment of primary refractory Hodgkin's disease. Retrospective study of the Polish Lymphoma Research Group.

We analysed the treatment outcome of primary refractory HD patients managed with high-dose chemotherapy and haematopoietic cell transplantation. Data of 65 adult patients who underwent HDC/ASCT in nine Polish centres for primary resistant Hodgkin's disease between June 1991 and July 2000 were collected retrospectively. Response rate to HDC/ASC: CR, 54%; PR, 20%; less than PR, 15%; early deaths, 11%. Actuarial 3-year OS and PFS were 55% and 36%, respectively. In multivariate analysis, lack of bulky lymph nodes and use of immunotherapy were favourable factors for both OS and PFS. IPF <3 at the time of transplantation was predictive for PFS. However, the prognostic impact of immunotherapy should be interpreted with caution since this group included more patients who achieved CR after HDC/ASCT. The results of HDC/ASCT are encouraging and confirm earlier findings. The role of immunotherapy should be further investigated in prospective trials.

[Autologous peripheral blood stem cell transplantation as an effective treatment for recurrent Hodgkin's disease]. / Autologiczna transplantacja komórek macierzystych z krwi obwodowej jako skuteczny sposób leczenia nawrotowej ziarnicy zlosliwej.

Autologous peripheral blood stem cell transplantation (APBSCT) is a method used analogically to autologous bone marrow transplantation (ABMT) to obtain hematological reconstitution following myeloablative therapy in patients with hematological malignancies. We have now applied this procedure in two patients with recurrent high risk Hodgkin's disease. Collection of circulating stem cells mobilised with cyclophosphamide/G-CSF was performed by several leukaphereses on Fenwal 3000, with access through inferior vena cava. Nucleated cells were separated by dextran sedimentation, cryopreserved, and stored at (-) 196 degrees C. Additional marrow collection was performed in one patient. Conditioning regimen consisted of BCNU, etoposide and cyclophosphamide delivered at days -3 and -2. Collected material containing on average 3.6 x 10(8)/kg nucleated cells and 8.0 x 10(6)/kg CD34(+) cells was transfused at day 0. G-CSF was administered following transplantation to one patient to hasten the recovery. Hematological recovery was relatively quick. Neither serious adverse events nor signs of relapse were observed following transplantation. Our results supported by other's reports indicate, that APBSCT enables hematological recovery similarly to ABMT in Hodgkin's disease. The advantage of APBSCT is a possibility to collect material in patients with marrow involvement, hypoplasia or fibrosis. Outcomes obtained following APBSCT are at least as good as following ABMT. High-dose chemotherapy followed by APBSCT or ABMT should be considered in all patients with recurrent Hodgkin's disease sensitive to chemotherapy.

[Central nervous system relapses in acute lymphoblastic leukemia and different methods of prophylaxis]. / Wznowy w osrodkowym ukladzie nerwowym w przebiegu ostrej bialaczki limfoblastycznej a sposób postepowania profilaktycznego.

The results of two different methods of CNS prophylaxis during consolidation were evaluated among fifty one acute lymphoblastic leukemia patients (ALL) treated in 1980-1991 in the Department of Hematology in Katowice. In group I (n = 28) methotrexate (Mtx) was used intrathecally (it) in 6 doses of 18 mg, in group II high dose cytosine arabinoside (Hi AraC)--3g/m2 intravenously (4x) was used with CNS rtg--therapy (18-24Gy). In both groups frequency of CNS relapses was similar 17.8% vs 17.3%; additionally there were no statistically significant differences in RFS: 369 vs. 562 days. The survival of patients with and without CNS relapses was also similar (678 vs. 774 days) and was independent of prophylaxis. The tolerance of both the used methods of CNS prophylaxis was good.

Autologous peripheral blood stem and progenitor cells transplantation as a valid treatment approach in recurrent, refractory lymphoma.

Autologous peripheral blood stem cell transplantation (APBSCT) is used similarly to autologous bone marrow transplantation (ABMT) to reconstitute bone marrow following myeloablative therapy in patients with proliferative diseases of the blood. Eight patients with recurrent and refractory lymphoma (3 HD, 4 NHL) and multiple myeloma aged 17-55 were included into the study. Peripheral blood stem cells following their prior mobilisation with cyclophosphamide 4-7 g/m2 and/or G-CFS or Dexa-BEAM + G-CSF were collected by subsequent leukaphereses on Fenwal CS3000. Nucleated cells were separated by sedimentation, cryopreserved in a programmed freezer and then stored at-196 degrees C. Bone marrow has been additionally collected in one patient. Conditioning treatment prior to transplantation consisted of BCNU, etoposide and cyclophosphamide (CBV) in lymphomas and melphalan in multiple myeloma. Collected material with mean cellularity 5.52 x 10(8)/kg and mean CD34+ contents 6.27 x 10(6)/kg was reinfused by central line. G-CSF was given in 5 patients to hasten the bone marrow recovery. All patients fully recovered and left hospital on average 35.5 days following transplantation. No signs of relapse were seen throughout the observation period (mean 349.5 days). Neutrophils > 0.5 G/1 were obtained on day + 20, > 1.0 G/1 on day 30, platelets > 50 G/1 on day 29, > 100 G/1 on day 53, reticulocytes > 0.015 on day 30, erythrocytes transfusions were needed up to day 39. Presented outcomes together with other reports indicate, that APBSCT is a highly efficient way to rescue repeatedly relapsing patients with proliferative diseases of the lymphatic systems, even those presenting with changes in the bone marrow (neoplasmatic infiltrate, hypoplasia or fibrosis).

[Results of induction treatment with idarubicin for acute nonlymphoblastic leukemia in adults]. / Wyniki leczenia indukujacego programu z uzyciem idarubicyny w ostrych biallaczkach nielimfoblastycznych u doroslych.

Fifty six adult acute nonlymphoblastic leukemia patients were randomised in 1993 year according to Polish Acute Leukemia Group (PALG) into prospective, cooperative trial with the same prognostic factors distribution. The results of induction treatment using idarubicin on days 1, 3, 5 plus arabinoside cytosine 1-7/10 plus etoposide 1-5 (ICE7/10) vs. daunorubicin on days 1-3 plus Ara-C 1-7/10 with additional HD Ara-C in case of not sufficient cytoreduction in 6th day's bone marrow biopsy (3+7/+/-HD) and etoposide in M4-5 subtype are comparable (63 vs. 61% CR). Complete remission was achieved significantly more frequency (p < 0.02) after 1 cycle of induction treatment with ICE7/10 (93%) compared with 3+7+/-HD (55%), and 10 days shorter time to CR was observed. Side effects were comparable in both groups. The program with IDA needed more intensive supportive therapy.

Childhood acute lymphoblastic leukemia immunophenotypes and their prognostic significance: experience of the IGCI-study in 389 children. International Society for Chemo-immunotherapy (IGCI-Vienna) Cooperative Group.

The prognostic significance of immunophenotype and other features including sex, age, anaemia, WBC, FAB type, and PAS staining were analysed in a group of 389 children newly diagnosed as acute lymphoblastic leukemia (ALL) and treated according to the BFM 1981/1983 protocol. The CR rate was higher (82-94%) in immunophenotypic subgroups defined as 'non-B' compared with B-ALL (54%). The probability of being in CCR at the end of follow up was 0.68 (median. observation, 3 years). Using the stepwise Cox regression analysis the following independent factors predictive of duration of CCR were selected (relative risk in brackets): 1. WBC (> 25G/1:< 25G/1 = 2.0, P = 0.0008), 2. age (> 10y:2-10y = 1.3, P = 0.04), 3. CALLA positivity (neg.:posit. = 2.4, P = 0.04), 4. CALLA within B-cell progenitor ALL (pre;preB,Calla-:Calla+ = 1.7, P = 0.007). T-ALL appeared to have a worse prognosis than U-ALL and B-progenitor derived ALL but it did not retain independent prognostic significance in multivariate analysis.

[Pancytopenia as a complication of the treatment of toxoplasmosis]. / Pancytopenia jako powiklanie leczenia toksoplazmozy.

Therapeutical doses of pyrimethamine are very close to toxic ones. Pyrimethamine is widely used in toxoplasmosis therapy. Hematological complications following pyrimethamine administration were seen in 4 patients treated for toxoplasmosis at our hospital in the last year. Pancytopenic syndrome was diagnosed in all four cases. Three patients recovered completely whereas ITP is persisting in one patient.

[Hemolytic anemia caused by excessive use of analgesics]. / Niedokrwistosc hemolityczna wywolana naduzywaniem leków przeciwbólowych.

A 40-year-old female patient is reported who gave a history of analgesics abuse (phenacetin) and had haemolytic anaemia. The probable mechanism of the toxic effect of phenacetin on the haemopoietic system through induction of intravascular haemolysis (so called stibophen-type haemolysis) is discussed. One-year follow-up demonstrated the reversibility of these haematological changes.

Skin manifestation of extramedullary relapse in adult with acute lymphoblastic leukaemia.

In the group of 75 ALL patients treated between 1980 and 1989, two women (ages 25 and 17, both FAB-L2 and CALLA +, after 56 and 34 months of continuous CR, respectively) were found to have a relapse manifested as a local infiltration of skin, with involvement of the adjacent lymph nodes in one patient. The leukaemic character of the skin infiltration was confirmed by skin needle aspiration and tissue biopsy expressing CD10 and CD24. Both patients were given intensified systemic chemotherapy and local X-ray irradiation. Complete remission was obtained with the disappearance of the skin infiltrations followed after 13 and 8 months, respectively, followed by a marrow relapse with symptoms of CNS involvement in one case. Both patients died because of treatment resistance (the overall survival time equalled 70 and 44 months, respectively).