Autologous stem cell transplantation for high-risk Hodgkin's disease: improvement over time and impact of conditioning regimen.

BACKGROUND AND OBJECTIVE: 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. DESIGN AND METHODS: 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). RESULTS: 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. INTERPRETATION AND CONCLUSIONS: 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.

Littoral cell angioma with severe thrombocytopenia.

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.

Salvage chemotherapy with IAPVP-16 for advanced refractory or relapsed follicular lymphomas.

BACKGROUND AND OBJECTIVE: 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. DESIGN AND METHODS: 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. RESULTS: 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). INTERPRETATION AND CONCLUSIONS: . 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.

Intensive salvage chemotherapy for primary refractory or first relapsed adult acute lymphoblastic leukemia: results of a prospective trial.

BACKGROUND AND OBJECTIVE: Adults with primary refractory or relapsed acute lymphoblastic leukemia (ALL) have a very poor prognosis with current salvage chemotherapies. Complete remissions (CR) can be obtained with intensive regimens in 40-60% of cases, but they are short-lived. In an effort to obtain high CR rates and prolong their duration and achieve long-term survival in a substantial number of patients, we designed an intensive combination salvage regimen (RELAL-88). In this protocol, chemotherapy was to be followed by an allogeneic or autologous stem cell transplant (SCT) within three months from CR. DESIGN AND METHODS: Forty-five patients with primary refractory (n=17) or first relapsed ALL (n=28) were treated with the RELAL-88 five-day induction regimen comprising vindesine, mitoxantrone, cyclophosphamide, intermediate-dose Ara-C, prednisolone and methotrexate. Twenty-eight patients received granulocyte colony-stimulating factor (G-CSF), 16 patients from day 6 (early G-CSF group) and 12 from day 14 of therapy (delayed G-CSF group). RESULTS: Thirty-four patients (74%) achieved CR (95% CI 60-87), two died in aplasia due to infection and nine were non-responders. No pretreatment variable analyzed was predictive of the chance of obtaining CR. Recovery of neutrophils occurred at a median of 29 days from the start of chemotherapy without G-CSF and 20 days with G-CSF (p = 0.005), without differences between the early and late G-CSF groups. Non-hematologic side effects were usually well tolerated and consisted mainly of infections and mucositis. Twenty-three of 34 patients (68%) who achieved CR reached the planned SCT (nine autologous and 14 allogeneic). The median overall survival was 5.7 months, and the median disease-free survival for those achieving CR was 4.6 months. Of the variables analyzed for their influence on overall survival among the 34 patients who achieved CR, only the availability of an HLA-compatible sibling was associated with a prolonged survival (p = 0.03). INTERPRETATION AND CONCLUSIONS: The RELAL-88 intensive salvage regimen produces a very high rate of CR in poor-risk adult ALL. Non-hematologic toxicities were tolerable, and most eligible patients could undergo the planned SCT. G-CSF significantly shortened the period of neutropenia by about eight days, irrespective of whether it was started early or late after chemotherapy. However, as with other currently available salvage therapies, remissions were short-lived, and more effective post-remission treatment strategies are needed. In our experience, only allogeneic SCT offered the chance of long-term survival.

Low-dose amphotericin B lipid complex for the treatment of persistent fever of unknown origin in patients with hematologic malignancies and prolonged neutropenia.

We studied the safety of low-dose amphotericin B lipid complex (ABLC, at 1 mg/kg/day) in 30 persistently febrile (>38 degrees C for at least 5 days or with recurrent fever after 3 days of apyrexia) and neutropenic (<0.5 x 10(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 <130 micromol/l and <11 mmol/l, respectively, in all cases. Liver enzymes showed modest but significant increases in most patients during therapy, while bilirubin decreased in 74% of cases. Response to treatment (defervescence within 6 days without developing a fungal or nonfungal infection) was seen in 22 cases (73%, 95% CI 58-89%), while 8 episodes were considered treatment failures: 2 due to persistent FUO, 1 withdrew due to IRAE, 2 developed nonfungal infections and 3 developed a presumed or definite invasive mycosis. We conclude that low-dose ABLC is very safe and well tolerated and seems as effective as c-AmB for this indication. Thus, randomized trials at this dose level appear justified to demonstrate any real benefit over c-AmB or other lipid formulations for the treatment of FUO in neutropenic patients.

Allogeneic bone marrow transplantation for advanced Waldenstrom's macroglobulinemia.

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.

Effect of discontinuing prophylaxis with norfloxacin in patients with hematologic malignancies and severe neutropenia. A matched case-control study of the effect on infectious morbidity.

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).

Allogeneic or autologous stem cell transplantation following salvage chemotherapy for adults with refractory or relapsed acute lymphoblastic leukemia.

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.

Late intensification chemotherapy has not improved the results of intensive chemotherapy in adult acute lymphoblastic leukemia. Results of a prospective multicenter randomized trial (PETHEMA ALL-89). Spanish Society of Hematology.

BACKGROUND AND OBJECTIVE: 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. DESIGN AND METHODS: One hundred and eight adults (age > or = 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. RESULTS: 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. INTERPRETATION AND CONCLUSIONS: 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.

Achromobacter xylosoxidans bacteremia in patients with hematologic malignancies.

We report nine cases of Achromobacter xylosoxidans bacteremia diagnosed in patients with hematologic malignancies. There was not an obvious epidemiologic link between cases and the organism was not isolated from any source. Outcome was cure in all nine cases. In our experience, catheter removal is generally required for eradication of A. xylosoxidans.

Autologous stem cell transplantation for poor prognosis Hodgkin's disease in first complete remission: a retrospective study from the Spanish GEL-TAMO cooperative group.

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 recover >0.5 x 10(9)/l neutrophils and >50 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.

Risk of reactivation of a recent invasive fungal infection in patients with hematological malignancies undergoing further intensive chemo-radiotherapy. A single-center experience and review of the literature.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. INTERPRETATION AND CONCLUSIONS: 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.

Successful treatment of pure red cell aplasia after major ABO-incompatible T cell-depleted bone marrow transplantation with erythropoietin.

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.

Low-dose donor CD8+ cells in the CD4-depleted graft prevent allogeneic marrow graft rejection and severe graft-versus-host disease for chronic myeloid leukemia patients in first chronic phase.

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 of >30 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.

Meropenem versus ceftazidime plus amikacin in the treatment of febrile episodes in neutropenic patients: a randomized study.

BACKGROUND AND OBJECTIVE: Meropenem is the first of a new class of carbapenems which may be administered without cilastatin. This study was performed to assess the clinical efficacy and tolerability of meropenem monotherapy (1 g/8 h) compared with the standard combination of ceftazidime (2 g/8 h) plus amikacin (15 mg/kg/day) for the empirical treatment of infective febrile episodes in neutropenic cancer patients. METHODS: This was a three-center, randomized, non-blind parallel group trial. The primary objective was to compare the clinical efficacy of meropenem monotherapy with that of ceftazidime plus amikacin in the empirical treatment of febrile infective episodes in neutropenic patients. This was evaluated by the number of patients surviving on unmodified therapy at 72 h (primary end point) and by the clinical response at the end of therapy (secondary end point). RESULTS: A total of 93 febrile episodes (46 meropenem, 47 ceftazidime/amikacin) were evaluable. Bone marrow transplant patients accounted for 49.5% of all cases. There was a high incidence of Gram-positive infections but no pseudomonal infections. Microbiologically documented infections, clinically documented infections and unexplained fever accounted for 45%, 10% and 45% of episodes, respectively. There was a similar proportion of patients in the meropenem and ceftazidime/amikacin groups on unmodified empiric therapy at 72 h (80.4% vs 76.6%, p = 0.65,) and cured at the end of therapy (37% vs 36.2%, p = 0.9). No significant difference in tolerability was observed between the groups. Meropenem was well tolerated; of note, there were no cases of nausea/vomiting or seizure related to its use. INTERPRETATION AND CONCLUSIONS: Meropenem monotherapy was well tolerated and produced response rates similar to those obtained with ceftazidime/amikacin. The low overall success rates with both treatments concur with those of other recent studies and are probably due to a combination of several factors, including the adoption of strict assessment criteria.

Transplantation of peripheral blood progenitor cells from HLA-identical sibling donors. European Group for Blood and Marrow Transplantation (EBMT).

Transplantation of peripheral blood progenitor cells (PBPCs) has largely replaced autologous bone marrow transplantation. The same might occur in the allogeneic setting if the favourable initial experience with allogeneic PBPCT is confirmed. We analysed all primary transplants utilizing unmodified PBPC from HLA-identical sibling donors reported to the European Group for Blood and Marrow Transplantation (EBMT) for 1994. 59 patients with a median age of 39 years received myeloablative therapy for acute myelogenous leukaemia (23 patients, acute lymphoblastic leukaemia (13), chronic myelogenous leukaemia (nine), lymphoma (seven), or other diagnoses (seven) mostly of advanced stages followed by transplantation of allogeneic PBPC. Three patients died soon after grafting, the others showed prompt haemopoietic recovery with median times to recover an absolute neutrophil count (ANC) above 0.5 and 1.0 x 10(9)/I of 15 (range 9-27) and 17d (range 10-28) respectively. Time to platelet recovery above 20 or 50 x 10(9)/I was 16 (range 9-76) and 18d (range 12-100) respectively. 27 patients (46%) developed no or mild acute graft-versus-host disease (GVIID). The incidence of moderate (grade II) disease was 27%; 24% of the patients developed severe acute GVHD (grades III or IV), 55% of patients who were alive 90d after transplantation developed chronic GVHD, the probability to develop extensive chronic GVHD was 32% (95% confidence interval 22-42) with a median follow-up of 14 months. Overall and event-free survival (EFS) at 1 year were 54% (CI 48-60) and 50% (CI 43-57), respectively, the relapse incidence was 23% (CI 17-29). EFS was 67% (CI 55-79) in patients transplanted for acute leukaemias in first complete remission, chronic myelogenous leukaemia in first chronic phase, or severe aplastic anaemia. Transplantation of allogeneic PBPC resulted in prompt and durable engraftment. The incidence and severity of acute and chronic GVHD seemed comparable to that observed after allogeneic BMT. Overall and event-free survival in this cohort of patients, most of whom suffered from advanced leukaemia or lymphoma, is encouraging, suggesting that the high numbers of T lymphocytes and/or natural killer cells contained in a typical PBPC collection product exert a vigorous graft-versus-leukaemia effect. Further evaluation of allogeneic PBPCT is highly desirable.

Tuberculosis in bone marrow transplant recipients: report of two cases and review of the literature.

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.

Mobilization of peripheral blood progenitor cells by cyclophosphamide and rhGM-CSF in multiple myeloma.

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.

Allogeneic peripheral blood progenitor cell transplantation: analysis of short-term engraftment and acute GVHD incidence in 33 cases. allo-PBPCT Spanish Group.

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 to >0.5 (>1) x 10(9)/l, day 14 (15); platelets to >20 (>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%).