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Littoral cell angioma (LCA) is a recently described splenic vascular tumor. We present a new case in a 62-year-old woman with severe thrombocytopenia and mild bleeding diathesis, but without palpable splenomegaly. Abdominal ultrasound and magnetic resonance showed multiple nodular images, suggesting splenic hemangiomas. A platelet kinetic study revealed a very short platelet survival. As the spleen was the site of platelet destruction, splenectomy was carried out. Histopathological and immunohistochemical data allowed a final diagnosis of LCA. Following splenectomy, the patient showed a transitory normalization of the platelet counts. Thrombocytopenia then reappeared but was moderate, without hemorrhagic diathesis. A second platelet kinetic study, performed 16 months post-splenectomy, showed hepatic platelet destruction. However, there were no macroscopic hepatic lesions in a second abdominal magnetic resonance study. This case illustrates the difficulties involved in determining the etiology of many peripheral thrombocytopenias.

We studied the safety of low-dose amphotericin B lipid complex (ABLC, at 1 mg/kg/day) in 30 persistently febrile (>38°C for at least 5 days or with recurrent fever after 3 days of apyrexia) and neutropenic (9/l) adult patients with hematologic malignancies. The median age was 45 years (range 18–67), most (60%) had an acute leukemia and all had fever of unknown origin (FUO). The total duration of neutropenia was a median of 17 days (range 9–33), and the total number of days with fever 10 days (range 6–39). Seven patients experienced mild-to- moderate infusion-related adverse events (IRAE). The serum creatinine and urea increased from baseline to end of therapy in 76 and 63% of cases, but the maximum levels reached were

Over a 9-year period 37 consecutive adults with primary refractory (n = 13) or first relapse of ALL (n = 24) received an intensive salvage chemotherapy regimen with the final intention of undergoing stem cell transplantation (SCT). Twenty-nine patients who achieved complete remission (CR) were assigned to receive autologous SCT (autoSCT) or allogeneic SCT (alloSCT) based on age and availability of a histocompatible sibling. Of the 19 patients assigned to autoSCT, 10 did not reach the transplant due to early relapse (n = 9) or fungal infection (n = 1), and nine were transplanted a median of 2.5 months (1–8) from CR, eight with an immunologically purged graft. One patient died early from ARDS and eight relapsed 2–30 months post-SCT. Three of the 10 patients assigned to alloSCT relapsed early, but all 10 received the assigned transplant a median of 2.5 months (1–7) from CR. Four died from transplant-related complications 0.7–12 months post- SCT, and six are alive and disease-free 9.7–92.6 months after the procedure. In an intention-to-treat analysis, the mean overall survival from CR for those assigned to autoSCT and alloSCT are 11.3 months (0.5–34.3) and 60.1 (2.3–98.3), respectively (log-rank, P < 0.01). only 65% of patients who reached cr and 51% of the initial 37 cases underwent the intended sct. we conclude that few adults with refractory or relapsed all actually reach sct in cr even when the protocol used is designed for this purpose. autosct appears to offer little benefit in this setting, and an allosct from a related or unrelated donor should be rapidly pursued after achieving cr.

The use of fluorinated quinolones for prophylaxis of infections in neutropenic cancer patients has led to a reduction of infections with gram-negative enteric bacilli, but there is concern about the emergence of antibiotic-resistant enterobacterial infections and a rise of gram-positive bacteremias. Due to these concerns, in mid-1995 the use of prophylactic norfloxacin was discontinued in our unit. In order to evaluate the impact of this measure on the infectious morbidity in our unit, 91 severe neutropenic episodes in 58 patients with hematologic malignancies who did not receive norfloxacin prophylaxis (NO group) were closely matched to 91 episodes in 60 patients who received norfloxacin prophylaxis (NORFLO group). There were no differences in the incidence of febrile neutropenia, fever of unknown origin or bacteremia during the first febrile episode. There was a trend for a higher rate of coagulase-negative staphylococcal bacteremia in the NORFLO group (5 vs. 11 cases in the NO and NORFLO groups, respectively, p = NS). Enterobacterial bloodstream infections were more frequent in the NO group (13 vs. 2 cases, respectively, p = 0.01), especially Escherichia coli (9 vs. 1 case, respectively, p = 0.01). Twelve of 13 enterobacterial isolates in the NO group were sensitive to the fluoroquinolones vs. 0/2 in the NORFLO group (p = 0.07). We conclude that the abrupt discontinuation of norfloxacin prophylaxis in our ward led to a rapid increase in the rate of fluoroquinolone-susceptible enterobacterial infections, with a scarce impact on infectious morbidity. This suggests that the selection of resistant flora in an inpatient ward by prophylactic antimicrobials may be reversible following the discontinuation of the prophylactic agent(s).

Nineteen adults with primary refractory or relapsed acute leukemia (12 ALL and 7 ANLL) were treated with an intensive salvage chemotherapy (intermediate-dose ara-C, intermediate-dose methotrexate, vindesine, cyclophosphamide, mitoxantrone and prednisolone) followed by a hematopoietic growth factor (HGF), either granulocyte colony-stimulating factor (5 micrograms/kg) or granulocyte-macrophage colony-stimulating factor (10 micrograms/kg). Both were given from the day after chemotherapy ended and until the neutrophil count rose above 1 X 10(9)/l for three consecutive days. Eleven patients (58%, 95% CI 33% to 82%) achieved complete remission, and 15 courses of salvage therapy were given to these complete responders. In a historical control group that did not receive HGF, 23 out of 38 patients (60%, 95% CI 44% to 77%) achieved complete remission, and 27 courses of therapy were delivered to complete responders. Treatment with a HGF accelerated the recovery of neutrophils to 0.5 X 10(9)/l significantly, shortening it from a mean of 28 to 22 days (p = .0002), with no effect on platelet recovery. There were no differences in the rates of documented and fatal infections, which were relatively high in both groups. In the patients with ANLL, there was no evidence that HGF accelerated leukemic regrowth. We conclude that HGF accelerates neutrophilic recovery following intensive salvage chemotherapy for acute leukemia, although no reduction in documented infections was found. Many factors, including the small patient sample, may have contributed to this latter finding.

SUMMARY. Cryptic antigens are detected by anti-bodies present in a wide spectrum of patients with or without thrombocytopenia, and even in healthy individuals. They are produced for unknown reasons and do not react with antigens of native platelets, but only with altered platelets. Cryptantigen antibodies may not only result in spuriously low platelet counts, but also in ‘falsely’ positive tests for platelet antibodies. We report our experience in the characterization of the different types of antibodies directed against cryptantigens of platelets: EDTA-dependent antibodies, PFA-dependent antibodies, EDTA-PFA-dependent antibodies and cold agglutinins. These antibodies were detected in the course of the serological study of 37 patients from a group of 356 (10%) whose blood was sent to our laboratory for platelet antibody testing. Pseudothrombocytopenia was diagnosed in 24 cases. Twenty-one of these showed EDTA-dependent or EDTA-PFA-dependent platelet agglutination and three were due to the presence of cold agglutinins. In 13 patients the thrombocytopenia was genuine. Eleven of these presented EDTA-dependent or EDTA-PFA-dependent antibodies in their serum and in the two remaining cases PFA-dependent antibodies were found. Cryptantigen antibodies were also detected in 9 out of 228 (4%) blood donors who were used as healthy controls in the platelet immunofluorescence test. In the light of the results obtained we put forward some guidelines to detect the presence of these antibodies and establish an accurate serological and clinical diagnosis of the autoimmune thrombocytopenias.

Of 320 patients receiving a marrow transplant at the Hospital de Sant Pau between 1986 and 1992, 12% developed viridans streptococcal bacteremia during severe neutropenia. Five of these patients (13%) developed a rapidly progressive fatal shock syndrome characterized by bilateral pulmonary infiltrates, acute respiratory failure (ARDS) and septic shock early in the transplantation course (6 or 7 days posttransplantation). All patients were transplanted for acute leukemia in remission, and 2 received an allogeneic and 3 an autologous transplant. Four of these subjects were younger than 15 years of age and all had received cyclophosphamide and total body irradiation as conditioning regimen for marrow transplantation. All 5 patients died, and postmortem examinations revealed diffuse pulmonary lesions characteristic of the ARDS. These observations contribute to defining the clinical and pathologic characteristics of this serious complication of intensive anticancer treatment.

Waldenstrom's disease is a lymphoproliferative disorder that is typically treated with plasmapheresis and/or alkylating agents. In young patients, other lymphoproliferative disorders have been treated with allogeneic transplantation. Two patients with aggressive Waldenstrom's disease, who progressed in spite of multi-agent chemotherapy and autologous stem cell transplantation, in one case, underwent allogeneic transplantation from their HLA-identical donors. Both remain alive with event-free survivals of more than 3, and more than 9 years, respectively. Allogeneic transplantation should be considered for young patients with Waldenstrom's disease.

High-dose chemo/radiotherapy with autologous stem cell support is increasingly being used in Hodgkin's disease (HD) patients who do not respond to or who relapse after conventional chemotherapy. In this work we analyze the results of 56 consecutive high-risk HD patients autografted in our institution and the role of possible prognostic factors.There were 34 males and 22 females with a median age of 31 years. At transplantation, 24 patients (43%) were in complete remission and 32 (57%) were autografted while with active disease. Twenty-nine patients were autografted before January 1993. Bone marrow was used as the source of stem cells in 40 patients (71%) and peripheral blood (PB) in 16 (29%). Forty-five patients received chemotherapy-based conditioning regimens (40 CBV and 5 BEAM) while the remaining 11 received cyclophosphamide (Cy) and total body irradiation (TBI).Two bone marrow transplantation (BMT) recipients did not engraft. Hematologic recovery was significantly faster in patients transplanted with PB progenitor cells. Early transplant-related mortality (early TRM) (before day 100 after transplantation) was 9%; it was higher in patients transplanted before January 1993 than in patients transplanted afterwards (14% vs 4%) and in patients receiving TBI (18% vs 7%), although these differences did not reach statistical significance. Overall TRM (before and after day 100) was 14%. TBI-containing regimens significantly increased overall TRM (36% and 9%, p = 0.03). Actuarial 3.5-year overall survival (OS), event-free survival (EFS) and progression-free survival (PFS) were 57%, 58% and 65%, respectively. On multivariable analysis, TBI containing regimens and transplantation before 1993 significantly reduced OS and EFS.Our results confirm that high-dose therapy followed by autologous stem cell transplantation is associated with sustained PFS in a remarkable proportion of patients with HD unlikely to be cured with standard chemotherapy. Results improved over time and TBI containing regimens had a negative effect on post-transplant outcome.

Patients with follicular lymphoma (FL) who do not respond to first-line chemotherapy or those who relapse after obtaining a remission have a poor outcome with standard treatment. In an effort to obtain a high rate of responses we designed an intensive brief duration salvage chemotherapy regimen.Forty-four consecutive patients with advanced follicular lymphoma were treated. Nine had primary refractory disease, 13 had achieved a partial remission, 16 were in untreated relapse or progression and six were in chemosensitive relapse. The IAPVP-16 regimen consists in ifosfamide 5 g/m(2) iv on day 1, etoposide 100 mg/m(2) iv on days 1-3, Ara-C 1.2 g/m(2)/12 hours iv on days 1-2 and methylprednisolone, 80 mg/m(2) iv on days 1-5. Granulocyte colony-stimulating factor was used from day 6 in 68 of 114 courses.Eighteen patients (41%) achieved a complete remission and 17 (39%) a partial remission, for an overall response rate of 80%. There were no treatment-related deaths. All treatment courses were followed by severe neutropenia, and 66% also by severe thrombocytopenia, but there were no serious hemorrhagic events. Neutropenic fever occurred in 56% of the courses with only four severe infections. Non-hematologic toxicity was modest. Twenty-eight patients proceeded to a stem cell transplantation. After a median follow-up of 25 months (range 4-95), the median progression-free survival and overall survival are 32 and 58 months, respectively. The median PFS was 33 months for responders and 11 months for non-responders (p=0.05), while the median OS has not been reached in responders and is 23 months in non-responders (p=0.0005).. The IAPVP-16 regimen is an effective and well tolerated treatment for advanced FL, allowing most eligible patients to proceed with significant tumor reduction to high-dose therapy and SCT.

The use of fluorinated quinolones for prophylaxis of infections in neutropenic cancer patients has led to a reduction of infections with gram-negative enteric bacilli, but there is concern about the emergence of antibiotic-resistant entero-bacterial infections and a rise of gram-positive bacteremias. Due to these concerns, in mid-1995 the use of prophylactic norfloxacin was discontinued in our unit. In order to evaluate the impact of this measure on the infectious morbidity in our unit, 91 severe neutropenic episodes in 58 patients with hematologic malignancies who did not receive norfloxacin prophylaxis (NO group) were closely matched to 91 episodes in 60 patients who received norfloxacin prophylaxis (NORFLO group). There were no differences in the incidence of febrile neutropenia, fever of unknown origin or bacteremia during the first febrile episode. There was a trend for a higher rate of coagulase-negative staphylococcal bacteremia in the NORFLO group (5 vs. 11 cases in the NO and NORFLO groups, respectively, p = NS). Enterobacterial bloodstream infections were more frequent in the NO group (13 vs. 2 cases, respectively, p = 0.01), especially Escherichia coli (9 vs. 1 case, respectively, p = 0.01). Twelve of 13 enterobacterial isolates in the NO group were sensitive to the fluoroquinolones vs. 0/2 in the NORFLO group (p = 0.07). We conclude that the abrupt discontinuation of norfloxacin prophylaxis in our ward led to a rapid increase in the rate of fluoroquinolone-susceptible enterobacterial infections, with a scarce impact on infectious morbidity. This suggests that the selection of resistant flora in an inpatient ward by prophylactic antimicrobials may be reversible following the discontinuation of the prophylactic agent(s).

Intensive induction and post-remission therapies have improved the prognosis in adult acute lymphoblastic leukemia (ALL). However, different from children, the impact of late intensification therapy in the overall results of treatment has not been consistently evaluated. The objective of this study was to analyze the results of a multicenter prospective protocol, PETHEMA ALL-89, in which, after intensive induction and consolidation therapy, randomization to receive delayed intensification treatment was performed.One hundred and eight adults (ageor = 15 years) diagnosed with ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with a five-drug induction therapy, followed by four cycles of early post-remission treatment during four months, and maintenance therapy for two years. Patients in remission at the end of the first year were randomized to receive one six-week cycle of late intensification therapy. Uni- and multivariate analyses of early response to treatment, complete remission (CR), leukemia-free survival (LFS) and overall survival (OS) were performed.The median (range) age of the series was 28 (15-74) years and leukocyte count 26 x 10(9)/L (1-600). ALL L1/L2 was present in 38/70 patients, early pre-B in 13, common in 53, pre-B in 12 and T in 30 cases. The CR rate was 86%, and refractory disease 9%. Median LFS was 34 months, with a 5-yr probability of 41% (95% CI, 29-53), whereas median OS was 51 months and 5-year probability 47% (34-59%). There were no differences in either LFS and OS between patients who did or did not receive delayed intensification therapy. Prognostic factors for CR attainment were advanced age and slow response to therapy. These two features were, in addition to high leukocyte counts, the parameters with negative influence in both LFS and OS.The results of PETHEMA ALL-89 are similar to those referred in other chemotherapy-based protocols in adult ALL. Delayed intensification has not improved the length of remission and survival. Efforts to improve the prognosis of adult ALL patients must be mainly focused in early intensification treatment.

A 40-year-old woman with acute myeloid leukemia in first remission developed pure red cell aplasia after a T cell-depleted ABO-incompatible bone marrow transplant from her HLA-identical sister. She remained transfusion-dependent for 11 months despite conversion of the ABO blood group to donor type, and titers of anti-donor isohemagglutinin being undetectable. Treatment with erythropoietin resulted in rapid improvement of the anemia with no further need for transfusions up to 21 months post-transplant. This case suggests that erythropoietin may provide effective therapy for pure red cell aplasia after ABO-incompatible bone marrow transplantation without the additional risks of further immunosuppression.

Based on previous experiences in animals and humans, low doses of CD8+ lymphocytes infused together with the marrow graft seem to enhance engraftment after allogeneic T cell-depleted marrow transplantation. From April 1994 to February 1997, 12 patients with chronic myelogenous leukemia in first chronic phase receiving a bone marrow transplant (BMT) from an HLA-identical sibling were included in a pilot study of T cell subset depletion. Total depletion of CD4+ cells of the marrow graft and partial depletion of CD8+ cells was performed by immunomagnetic separation. In order to improve the engraftment rate, we infused a low fixed number of CD8+ lymphocytes (0.25 x 10(6)/kg). All the patients were at high risk of developing acute graft-versus-host disease (GVHD), with a recipient age of30 years, and/or donor sensitized by previous pregnancies or transfusions. All of them received cyclosporin A and methotrexate post-BMT. No graft failure was observed. The grade III-IV GVHD rate was 16.6%, and the actuarial survival at 3 years is 81.8%. Immunological recovery showed persistent CD8+ HLA-DR+ lymphocytosis 8 months after transplant. Relapses were not observed. This experience shows the importance of CD8+ cells to ensure correct engraftment, decreasing the GVHD rate.

Although more than 50% of Hodgkin's disease patients are cured with conventional chemotherapy, many will relapse and eventually die from their disease. Many efforts have been made to identify poor prognostic factors that could be useful in selecting high-risk patients in 1st CR who may benefit from high-dose chemo/radiotherapy. However, the role of early transplantation in 1st CR remains unclear. We have retrospectively analyzed the results obtained with this procedure in 22 hospitals belonging to the Spanish GEL/TAMO cooperative group. Twenty-seven patients, of whom 19 were males, underwent autologous transplantation for Hodgkin's disease in 1st CR between January 1987 and January 1996. Remission had been achieved after one (n = 22) or two (n = 5) lines of treatment. Twenty-four patients had advanced stage disease, 12 patients bulky mediastinal disease, nine bone marrow involvement and 18 had extranodal disease. Peripheral blood was used as the source of hematopoietic stem cells in 15 patients, BM in nine, and both in three. All but three patients received chemotherapy-based conditioning regimens (16 CBV, four BEAM and four BEAC), while three were conditioned with CY and TBI. There were no transplant-related deaths. Median (range) times to recover0.5 x 10(9)/l neutrophils and50 x 10(9)/l platelets were 14 (8-56) days and 16 (8-240) days, respectively. With a median follow-up of 30 (8-66) months, 21 patients are alive and in continuous CR. Four patients who relapsed after transplant at 8, 17.5, 22 and 26 months achieved a second CR with conventional chemotherapy; one patient relapsed 92 months post-transplant and died 5 months afterwards. Another patient died 30.5 months post-transplant from a secondary malignancy. In conclusion, high-dose therapy in poor prognosis Hodgkin's disease in 1st CR was well tolerated with no transplant-related mortalities. Although the follow-up of this series is relatively short, our results seem promising. Nevertheless, late relapses can occur, and the role of this procedure vs conventional treatment in very high-risk patients should be assessed in prospective randomized studies.

Patients with hematologic malignancies and a history of an invasive fungal infection are considered to be at high risk of suffering reactivation of the infection during subsequent intensive chemotherapy.From January 1993 to September 1996, nine patients with a hematologic malignancy and previous invasive pulmonary aspergillosis (IPA) or Pseudallescheria boydii pneumonia and five with invasive candidiasis received further intensive chemotherapy (n = 3) or a bone marrow or peripheral blood stem cell transplant (n = 11) four days to 13 months (median three months) from the start of therapy for the fungal infection. Five patients with IPA and all five with invasive candidiasis showed complete or good partial radiologic resolution of the infection with the primary antifungal therapy given, which was continued before, during and after the period(s) of subsequent neutropenia.Twelve of the 14 patients showed no signs of progression or reactivation of the fungal infection during therapy, while two patients with active IPA died with progressive aspergillosis shortly after an allogeneic transplant. A review of the literature revealed that in both types of infections the risk of reactivation and dissemination appears low after achieving clinical and radiologic signs of response, which takes several weeks or months before proceeding to further antileukemic therapy.Despite lack of definite evidence, administration of an active antifungal drug before, during and after the period of neutropenia appears to be useful. In IPA, residual masses, nodules or cavities in the lung usually contain viable invasive fungal elements and should be resected whenever possible. On the other hand, the risk of reactivation and progression of an active fungal infection during intensive chemoradiotherapy is very high, and novel therapeutic strategies appear warranted in this setting.

Over a 6 year period we have seen two cases of tuberculosis among 118 allogeneic and 237 autologous bone marrow (BMT) or peripheral blood transplants. Both patients had received an HLA-identical related allogeneic BMT. The first case suffered from extensive chronic graft-versus-host disease (GVHD) and developed pulmonary tuberculosis 19 months after BMT. An open-lung biopsy was required to establish the diagnosis, and response to antituberculosis agents was complete, with no relapse at 49 months post-BMT. The second patient received a CD4+ T lymphocyte-depleted BMT, was receiving steroids for acute GVHD and developed rapid-onset meningeal tuberculosis on day +107 post-BMT. Despite initial severe neurologic deterioration, response to antituberculosis agents was good, and she remains alive and well 11 months from BMT. Review of the scant literature on this topic reveals that this is a relatively rare infection in BMT recipients despite their often severely immunosuppressed condition, occurring mainly in recipients of T cell-depleted allogeneic grafts or those who develop GVHD.

The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult patients with hematologic malignancies were analyzed in a retrospective and multicenter study. In 21 of 33 cases (63%) the disease was refractory or in advanced stage and eight of the 33 cases (24%) were second transplants after relapse. Donors were treated with a median of 10 (4-16) micrograms/kg/day of rhG-CSF subcutaneously for 5-7 days. Three required a central venous line for harvesting. Peripheral blood leukapheresis product contained a median of 5.9 (1.8-13) 10(6)/kg CD34+ cells and a median of 309.5 (153-690) 10(6)/kg CD3+ cells. After a myeloablative regimen, all patients received PBPC from HLA-identical donors as the sole source of progenitor cells. Cyclosporin A (CsA) alone (n = 2), CsA and steroids (n = 9), and CsA and methotrexate (MTX) (n = 22) were used for GVHD prophylaxis. Growth factors post-transplant were given to 11 patients (33%). The median follow-up of the patients was 3 months. Actuarial median day for hemopoietic recovery was: neutrophils to0.5 (1) x 10(9)/l, day 14 (15); platelets to20 (50) x 10(9)/l, day 14 (21). The quantity of CD34+ cells infused did not significantly affect the engraftment kinetics, from a starting cutoff of 2.5 x 10(6)/kg. The speed of neutrophil recovery seemed to be influenced strongly by using rhG-CSF post-transplant and marginally by the type of GVHD prophylaxis. Actuarial probability for grade II-IV acute GVHD of the whole group was 37% (95% Cl, 20-54%).

Twenty-six patients with hematological or solid tumors who developed bacteremia caused by Stenotrophomonas maltophilia (n = 10), Pseudomonas putida (n = 6), Sphingomonas paucimobilis complex (n = 4) or Alcaligenes xylosoxidans (n = 6) in the period between 1993 and 1995 were studied. Seventeen patients were neutropenic during the infection, and 13 were undergoing bone marrow or peripheral blood stem cell transplantation. Twenty-three patients had catheter-related infections; only 3 of the 26 patients developed septic complications (all due to Stenotrophomonas maltophilia). Twenty patients were cured following catheter removal, either as primary measure (n = 8) or salvage measure (n = 12). Four responded to antibiotic therapy only, and two died of septic complications. Such infections in hematological and oncological patients have increased in this hospital from no cases in 1975 to 11 cases in 1995.

Fifteen consecutive patients with multiple myeloma (MM) scheduled for peripheral blood progenitor cell (PBPC) transplantation, were randomly selected to receive cyclophosphamide (CY) (4 g/m2) alone (group I) or associated with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (5 micrograms/kg/day) (group II). The mean time of neutropenia after CY administration was 9.8 +/- 4.3 days in group I and 6.4 +/- 1.2 days in group II (P = 0.0228). One hundred and eight aphereses were performed (7.1 +/- 1.8 aphereses per patient in group I and 6.4 +/- 2.8 aphereses per patient in group II). rhGM-CSF administration after CY allowed a higher collection of CD34+ cells in apheresis products (1.42 +/- 1.68 x 10(6) CD34+ cells/kg) in comparison to without factor administration (0.47 +/- 0.52 x 10(6) CD34+ cells/kg) (P = 0.0165). The mean number of cells infused per patient was 6.56 +/- 4.02 x 10(8) MNC/kg and 7.64 +/- 3.00 x 10(4) CFU-GM/kg in group I and 6.25 +/- 4.03 x 10(8) MNC/kg and 8.16 +/- 9.73 x 10(4) CFU-GM/kg in group II. The mean time to recover 0.5 x 10(9) granulocytes/I, 20 and 50 x 10(9) platelets/I in peripheral blood (PB) was 17.2 +/- 7.4, 13.4 +/- 3.7 and 16.5 +/- 6.9 days respectively, in group I and 13.3 +/- 1.7, 11.6 +/- 1.6 and 15 +/- 6.3 days, in group II. rhGM-CSF administration after CY treatment for PBPC mobilization in MM patients reduces the neutropenic period after CY and enhances apheresis CD34+ cell collection.

Chimerism studies after allogeneic BMT are performed to determine the donor and/or recipient origin of peripheral blood and marrow lymphoid and hematopoietic cells. These studies have been performed mostly in leukemias and aplastic anemia. We report DNA-based chimerism studies in three patients transplanted for advanced CLL from a histocompatible sibling. Following conditioning with chlorambucil, cyclophosphamide and TBI all three successfully engrafted. One has remained in continuous complete remission (CR) with a complete donor chimerism (CDC) for 110 months post-BMT. Another was in mixed chimerism (MC) with minimal residual disease (MRD) at 3 months post-BMT but was in CR and in CDC at 6 months, suggesting that the persistent CLL cells has disappeared between these two studies. The third patient has been in persistent MC since BMT (24 months follow-up), although he is in CR with no evidence of persistent CLL. We postulate that this patient's MC status is due to normal residual recipient lymphohematopoietic cells that survived the conditioning regimen. In conclusion, various patterns of chimerism can be observed in CLL patients after BMT while remaining in CR and with no evidence of residual CLL.

Fourteen patients with acute nonlymphoblastic leukemia (ANLL) (n = 13) or juvenile chronic myelomonocytic leukemia (n = 1) were transplanted after conditioning with high-dose busulfan (4 mg/kg daily on days -7 to -4) and melphalan (180 mg/m2 on day -2). This protocol was designed for patients considered unable to receive standard conditioning regimens with cyclophosphamide and/or TBI. Five patients (4 children and 1 adult) received a second allogeneic BMT in untreated early marrow relapse after a first BMT. There were 3 procedure-related deaths (PRD), 2 during aplasia and 1 from acute GVHD. Two patients survived the procedure; 1 relapsed at 6 months and 1 is alive at 43+ months. Nine subjects (8 children and 1 adult) received an autologous BMT, 7 in first and 2 in second complete remission (CR). Of the 7 patients grafted in first CR, there was 1 PRD, 2 relapses at 3 and 15 months, and four are alive at 38 to 82+ months. One patient grafted in second CR relapsed at 7 months and 1 is alive at 67+ months. Toxicities were mild or moderate in autologous BMT recipients, mainly affecting the gastrointestinal tract. In the allogeneic BMT group, there were more moderate to severe toxicities, including 3 cases of moderate-severe renal toxicity; no cases of such toxicity were seen in ABMT recipients. Two cases of HVOD occurred, 1 in each group. These results are encouraging, although the small patient group does not allow any firm conclusions.

The effect of interferons in the correction of thrombocytosis in chronic myeloproliferative syndromes is well known. In this study the efficacy of alpha-2b interferon in a regimen of induction followed by a phase of sequential maintenance to progressively decreasing doses was evaluated with the aim of knowing the minimum doses necessary to maintain response.The response to treatment with alpha-2b interferon was prospectively studied in a group of 37 patients with chronic myeloproliferative syndromes with associated thrombocytosis (excluding chronic myeloid leukemia). Likewise, the toxicity of the treatment was analyzed.Sixty-seven percent of the patients responded (platelets lower than 600 x 10(9)/1) to the daily administration of 3 or 5 MU of interferon. Forty percent of the patients who responded to the daily schedule of administration maintained the response upon receiving 3 doses weekly for 4 months. Half of the 8 patients who received 2 weekly doses of interferon for 4 months continued maintaining the responses. Only two of the 4 patients who received one sole weekly dose during the following 4 months maintained the response. Only one of the 37 patients who initiated treatment underwent progression of the symptoms present at the beginning of the study. Toxicity was high and was the cause of 12 discontinuations of treatment (32% of the patients) during the daily treatment phase (9 patients) or during maintenance of 3 weekly doses (3 patients). No toxicity was observed in the schedule of one or two weekly doses.Alpha-2b interferon is effective in the treatment of thrombocytosis of the chronic myeloproliferative syndromes (excluding chronic myeloid leukemia) when administered daily and is ever less so when the doses are spaced at 3, 2 or 1 week. The toxicity of interferon treatment is high when administered at affective doses.

Twenty-nine adult patients with relapsed (21) or refractory (8) de novo acute leukemia (12 ALL and 17 ANLL) were treated with a remission-induction salvage chemotherapeutic protocol including vindesine, mitoxantrone, cyclophosphamide, intermediate-dose cytosine arabinoside, prednisolone and methotrexate. Ten of seventeen (59%) ANLL and 8/12 ALL (67%) achieved complete remission (CR). Seven of eight (86%) cases refractory to first-line remission-induction therapy (3/4 ANLL and 4/4 ALL) entered complete remission. The most frequent non-hematologic side effects were gastrointestinal. All patients experienced severe pancytopenia, with median times to recovery of granulocyte and platelet counts of 28 and 29 days, respectively. Nine of twenty-nine (31%) patients suffered febrile episodes of unknown origin and 13/29 (45%) suffered documented infections. Five patients (17%) died while aplastic, four from infection and one from cardiotoxicity. Four patients who entered CR were submitted to a bone marrow transplantation (BMT), two autologous and two allogeneic BMT. Sixteen of the 18 patients who entered CR relapsed, with a median remission duration of 3.5 +/- 2.9 months. Two patients remain in remission at 5+ and 17+ months. These results suggest that this protocol is an effective remission-induction salvage therapy for adult acute leukemias.

Between December 1st 1984 and July 1st 1991, 20 patients, 11 males and 9 females, median age 36 years (range 14-54) with Hodgkin's disease were treated with high dose chemo-radiotherapy followed by autologous bone marrow rescue. At the time of autologous bone marrow transplantation, 8 patients were in complete remission, 9 in sensitive relapse and 3 were resistant to conventional treatments. There were 3 early procedure-related deaths: 1 cardiac failure due to cyclophosphamide treatment, 1 veno-occlusive disease, and 1 patient died from CMV interstitial pneumonitis, 4 months after ABMT. Of the 17 other patients, 15 are alive, 12 in complete remission, 2 in relapse and 1 patient is not evaluable due to short-follow-up follow-up. Disease free survival is 65% at 20 months with a follow-up of 60 months. There is a trend for a better disease-free survival in patients in complete remission at the time of autologous bone marrow transplantation vs patients in sensitive relapse, although it does not reach statistical significance (80% vs 37%).

Eleven patients with Hodgkin's disease were treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Four patients were resistant to initial therapy and 7 patients had relapsed but were progressing under second or third line therapy. The median time from initial diagnosis to transplantation was 44 months (range, 16 to 82). In 9 patients pre-ABMT consisted on high-dose CVB cyclophosphamide, etoposide and carmustine) chemotherapy, one patient was treated with BACT protocol (carmustine, cytosine arabinoside, cyclophosphamide and thioguanine) and other patient was treated with high-dose of busulfan and melphalan. In 8 patients complete remission (CR) was achieved, in one the remission was partial, one failed to respond and one case was not evaluable due to early death. Among CR patients, 2 died from late toxicity, and the other 6 remain in CR off therapy, one of them more than 33 months after ABMT. High-dose therapy produce severe myelosuppression in all patients. There were 3 treatment related death: one early death due to hemorrhagic myocarditis, one veno-occlusive disease of the liver and one due to cytomegalovirus sepsis. The high complete response rate in these heavily pretreated patients suggests that there may be an indication for high-dose therapy and ABMT in earlier resistant Hodgkin's disease. Moreover under such conditions, treatment related morbidity would be expected to be lower.

A 20-year-old male underwent an allogeneic bone marrow transplantation for acute myelogenous leukemia after conditioning with cyclophosphamide and total body irradiation. On day + 6 of the procedure, he developed fever, chills and myalgias. Empiric treatment with ceftazidime and amikacin was begun, and blood cultures grew viridans streptococci. Biochemical changes suggestive of acute rhabdomyolysis were evident. Within 24 h, adult respiratory distress syndrome with multiorgan failure appeared, and he died 7 days later. At autopsy, the presence of rhabdomyolysis was confirmed.