Low-dose lenograstim is as effective as standard dose in shortening neutrophil engraftment time following myeloablative chemotherapy and peripheral blood progenitor cell rescue

Granulocyte colony-stimulating factor (G-CSF) is widely used following myeloablative chemotherapy (high-dose therapy; HDT) and peripheral blood progenitor cell rescue (PBPCR) to reduce neutrophil engraftment time. The dose and duration required to gain maximum clinical and economic benefit has not been fully investigated. This double blind placebo-controlled randomised trial was performed to determine whether short course low-dose or standard-dose Lenograstim (L) would influence recovery of haematopoiesis following HDT and PBPCR. Sixty-one patients were randomised between May 1999 and November 2004, to receive standard-dose lenograstim (263 microg/d), low-dose lenograstim (105 microg/d) or placebo injections. These commenced on day +5 following PBPCR and continued until neutrophil engraftment [absolute neutrophil count (ANC)] > or = 0.5 x 10(9)/l. Patients received standard supportive care until haemopoietic recovery. Both standard- and low-dose lenograstim resulted in a significantly shorter median time to neutrophil recovery (ANC > or = 0.1 x 10(9)/l:10.0 vs. 11.0 d, P = 0.025; ANC > or = 0.5 x 10(9)/l:11.0 vs. 14.0 d, P = 0.0002) compared with placebo. There was no significant difference in blood product support, antibiotic usage, documented infection, overall survival or relapse-free survival between the groups. Short course low-dose lenograstim is as effective as standard-dose in reducing neutrophil engraftment time following HDT and PBPCR.     

Pegfilgrastim after high-dose chemotherapy and autologous peripheral blood stem cell transplant: phase II study

Pegfilgrastim is equivalent to daily filgrastim after standard dose chemotherapy in decreasing the duration of neutropenia. Daily filgrastim started within 1-4 days after autologous stem cell transplant (ASCT) leads to significant decrease in time to neutrophil engraftment. We undertook a study of pegfilgrastim after high-dose chemotherapy (HDC) and ASCT. In all, 38 patients with multiple myeloma or lymphoma, eligible to undergo HDC and ASCT, were enrolled. Patients received a single dose of 6 mg pegfilgrastim subcutaneously 24 h after ASCT. There were no adverse events secondary to pegfilgrastim. All patients engrafted neutrophils and platelets with a median of 10 and 18 days, respectively. The incidence of febrile neutropenia was 49% (18/37). Neutrophil engraftment results were compared to a historical cohort of patients who received no growth factors or prophylactic filgrastim after ASCT. Time to neutrophil engraftment using pegfilgrastim was comparable to daily filgrastim and was shorter than in a historical group receiving no filgrastim (10 vs 13.7 days, P<0.001). Pegfilgrastim given as a single fixed dose of 6 mg appears to be safe after HDC and ASCT. It accelerates neutrophil engraftment comparable to daily filgrastim after ASCT. Pegfilgrastim may be convenient to use in outpatient transplant units.     

Is it safe to treat allogeneic stem cell transplant recipients at home during the pancytopenic phase? A pilot trial

After myeloablative treatment and allogeneic stem cell transplantation (ASCT), patients are kept isolated in the hospital to prevent infections during neutropenia. To date, 22 patients have been given the choice of being treated at home. Eleven could not be treated at home, and they served as controls. Most had haematological malignancies. The donors were 12 HLA-compatible unrelated, nine HLA-identical siblings and one twin. In the home care group, three developed bacteraemia, compared to nine in the controls (P < 0.01). Patients in the home care group had fewer days of total parenteral nutrition (median 3 vs 24, P < 0.001), required fewer erythrocyte transfusions (median 4 vs 8, P = 0.01), fewer days on i.v. antibiotics (median 6 vs 13 days), and on analgesics (median 0 vs 15) than the controls (P < 0.05). Days with fever, time to engraftment, days with G-CSF and acute GVHD were the same in the two groups. Seven of 11 patients treated at home were readmitted to the ward for a median of 3 (0-7) days, due to fever or lack of a caregiver at home. Days to discharge to the out-patient clinic were faster in the group treated at home (median 20 vs 35 days, P < 0.01). Patients who were treated at home enjoyed being active and taking a walk when they felt like it. This preliminary report suggests that home care after ASCT is not only safe, but superior to isolation in the hospital.     

ThaDD plus high dose therapy and autologous stem cell transplantation does not appear superior to ThaDD plus maintenance in elderly patients with de novo multiple myeloma

Objectives: With the aim to address the issue whether high‐dose therapy (HDT) is required after new drugs combinations to improve outcome of elderly newly diagnosed multiple myeloma (MM) patients, we compared the toxicity and the outcome of ThaDD plus maintenance to those of ThaDD plus HDT‐autologous stem cell transplantation (ASCT). Methods: Sixty‐two patients not eligible for HDT receiving six courses of ThaDD regimen plus maintenance with thalidomide were compared to 26 patients eligible for HDT treated with four courses of ThaDD followed by melphalan 100–200 mg/m² and ASCT. The two groups were matched for the main characteristics except for age favouring the HDT group. Results and conclusions: Complete remission (CR) obtained with ThaDD plus maintenance was 24% whereas it was 57% after ThaDD plus HDT‐ASCT (P = 0.0232). However, after a median follow‐up of 36 months, median time to progression (TTP) and progression free survival (PFS) of the group of patients undergone HDT were not significantly different to those of patients receiving ThaDD plus maintenance (32 vs. 31 months: P = 0.962; 32 vs. 29 months: P = 0.726, respectively). Five‐year overall survival (OS) was 49% in the first group and 46% in the latter one (P = 0.404). As expected, a significantly higher incidence of grade 3–4 neutropenia, thrombocytopenia, infections, mucositis and alopecia were observed in the ThaDD plus HDT group. Our results suggest that in elderly MM patients ThaDD plus HDT, albeit significantly increases CR rate, seems to be equivalent to ThaDD plus maintenance in terms of TTP, PFS and OS. These results challenge the requirement for HDT consolidation in this subset of patients.     

Improved haematopoietic recovery following transplantation with ex vivo-expanded mobilized blood cells

Infusions of ex vivo-expanded (EXE) mobilized blood cells have been explored to enhance haematopoietic recovery following high dose chemotherapy (HDT). However, prior studies have not consistently demonstrated improvements in trilineage haematopoietic recovery. Three cohorts of three patients with breast cancer received three cycles of repetitive HDT supported by either unmanipulated (UM) and/or EXE cells. Efficacy was assessed by an internal comparison of each patient's consecutive HDT cycles, and to 106 historical UM infusions. Twenty-one cycles were supported by EXE cells and six by UM cells alone. Infusions of EXE cells resulted in fewer days with an absolute neutrophil count (ANC) <0.1 x 10(9)/l (median 2 vs. 4 d, P = 0.002) and 3 d faster ANC recovery to >0.1 x 10(9)/l (median 5 vs. 8 d, P = 0.0002). This resulted in a major reduction in the incidence of febrile neutropenia compared with UM cycles (0% vs. 83%; P = 0.008) and in 66% of historical UM cycles (P = 0.01) and a marked reduction in hospital re-admission. There were also fewer platelet transfusions required (43% vs. 100%; P = 0.009). We conclude that EXE cells enhance both neutrophil and platelet recovery and reduce febrile neutropenia, platelet transfusion and hospital re-admission.     

Prophylactic antibiotics for the prevention of neutropenic fever in patients undergoing autologous stem-cell transplantation: results of a single institution, randomized phase 2 trial

One hundred and fifty-seven patients undergoing high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) for hematopoietic malignancies and solid tumors were randomly assigned to receive (Group A) or not (Group B) prophylaxis with ciprofloxacin, orally, and vancomycin, intravenously. Prophylactic antibiotics were given from day 0 until resolution of neutropenia or the appearance of a febrile event. Furthermore, patients in both groups received once a day fluconazole, orally. The primary end-point of our study was the incidence of neutropenic febrile episodes attributed to infection. One hundred and twelve (71.3%) patients developed neutropenic fever, 50 (56.2%) in Group A and 62 (91.2%) in Group B (P < 0.001) with the majority (82%) of patients developing fever of unknown origin. Patients on prophylactic antibiotics had a significantly lower rate of bacteremias (5.6%) than did those randomized to no prophylaxis (29.4%) (P = 0.005) and, when developing neutropenic fever, they had a lower probability of response to first-line empirical antibiotics (P = 0.025). Prophylactic administration of ciprofloxacin and vancomycin reduced the incidence of neutropenic fever in patients receiving HDT with ASCT, however, without affecting the total interval of hospitalization, time to engraftment, or all-cause mortality. Therefore, our results do not support the use of antibiotic prophylaxis for patients undergoing HDT and ASCT.     

Single-agent therapy with oral mercaptopurine for nonlymphoid blast crisis of chronic myeloid leukemia

Currently, no effective treatment is available for the nonlymphoid blast crisis (BC) of chronic myeloid leukemia (CML) and because of this the prognosis for such patients remains invariably poor. In an attempt to determine the results provided by palliative treatment with oral 6-mercaptopurine (6-MP) in the above hematological condition, 30 such patients were analyzed for hospital stay, days of intravenous (i.v.) antibiotics, transfusion requirements, response rate, and survival. Thirty patients with nonlymphoid BC matched for their initial characteristics and treated with different i.v. regimens were used for comparison purposes. Patients managed with 6-MP spent less days in hospital (median: 9, range: 0-46 vs median: 42, range: 5-140; P<0.0001), needed antibiotics for less days (median: 0. range: 0-46 vs median: 20, range: 0-57; P<0.0001), and received less platelet transfusions (median: 0, range: 0-20 vs median: 6, range: 0-63; P=0.004) than those treated with i.v. chemotherapy. Although no complete or partial remission was achieved by patients receiving 6-MP vs six in the i.v. chemotherapy group, no significant difference was observed when the survival of both groups was compared (median: 4.7 months, range: 0.1-22.7 vs median: 3.8 months, range: 0.2-12, respectively). These results indicate that 6-MP therapy constitutes a good palliative treatment for patients with nonlymphoid BC of CML. However, new treatment strategies for this hematological condition are required.     

A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.     

Results and follow-up of a phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia

In patients with idiopathic severe aplastic anaemia who are treated with immunosuppressive agents to combat T lymphocyte-mediated destruction of haematopoietic progenitor cells, neutropenia is a major cause of infections and toxicity. Evidence from preliminary studies suggests that recombinant human glycosylated granulocyte colony-stimulating factor (lenograstim) increases the number and functionality of neutrophils in patients with severe aplastic anaemia. This randomized, parallel-group, multicentre study was conducted to evaluate the efficacy and safety of subcutaneous lenograstim during the first 12 weeks of standard immunosuppressive therapy in 102 patients with de novo severe aplastic anaemia. The addition of lenograstim to standard therapy resulted in an increase in the proportion of patients showing complete neutrophil response (83.0%vs 44.9%; P < 0.0001). This was seen even among patients with very severe aplastic anaemia (69.2%vs 31.6%; P = 0.012). In patients receiving lenograstim, median time to complete neutrophil response was shorter (6.3 vs 16.1 weeks; P = 0.0001) and mean duration of first neutrophil response was longer (P = 0.0248) than in the control group. At a median follow-up of 5 years, no difference was observed between the groups in term of survival, haematological response and occurrence of secondary leukaemia (one patient in each group). We conclude that lenograstim support of immunosuppressive therapy might be used for patients with severe aplastic anaemia as it significantly enhances neutrophil recovery but does not modify the overall response and survival.     

A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone

We conducted a prospective randomised study to compare the efficiency of out-patient progenitor cell mobilisation using either intermediate-dose cyclophosphamide (2 g/m(2)) and lenograstim at 5 micrograms/kg (Cyclo-G-CSF group, n=39) or lenograstim alone at 10 micrograms/kg (G-CSF group, n=40). The end points were to compare the impact of the two regimens on mobilisation efficiency, morbidity, time spent in hospital, the number of apheresis procedures required and engraftment kinetics. Successful mobilisation was achieved in 28/40 (70%) in the G-CSF group vs 22/39 (56.4%) for Cyclo-G-CSF (P=0.21). The median number of CD34+ cells mobilised was 2.3 x 10(6)/kg and 2.2 x 10(6)/kg for G-CSF and cyclo-G-CSF arms following a median of two apheresis procedures. Nausea and vomiting and total time spent in the hospital during mobilisation were significantly greater after Cyclo-G-CSF (P<0.05). Rapid neutrophil and platelet engraftment was achieved in all transplanted patients in both groups. In conclusion, G-CSF at 10 micrograms/kg was as efficient at mobilising progenitor cells as a combination of cyclophosphamide and G-CSF with reduced hospitalisation and side effects and prompt engraftment. When aggressive in-patient cytoreductive regimens are not required to both control disease and generate progenitor cells, the use of G-CSF alone appears preferable to combination with intermediate-dose cyclophosphamide.     

Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.     

Clinical outcome of granulocyte transfusion therapy for the treatment of refractory infection in neutropenic patients with hematological diseases

Neutropenic patients with hematological diseases are prone to severe infections. Granulocyte transfusion therapy (GTX) is considered as a logical therapeutic approach for these problems. However, the efficacy and complications of GTX have not been well identified. We retrospectively analyzed the clinical outcomes of GTX therapy in our hospital from 2009 to 2015. After 117 granulocyte transfusions for 47 patients, 72.3% of these patients’ infections were effectively improved, and the overall survival rates at 30 and 120 days were 66.0 and 57.5%, respectively. The patients who experienced neutrophil recovery within 10 days after their therapy initiation had a better response and long-term survival period (14/15, 93.3%, vs 20/32, 62.5%, P?=?0.037). Higher-dose granulocytes (>?2.55?×?10⁸/kg) might improve the effective rate of infection in the patients who had more than 10 days neutrophil recovery time (17/23, 73.9%, vs 3/9, 33.3%, P?=?0.049). In addition, GTX benefited the patients who suffered from pulmonary bacterial infections (16/20, 80%) compared with the bloodstream infection group (7/12, 58.3%) and skin or mucous infection group (1/5, 20%). The primary data showed that GTX did not affect the incidence of graft-versus-host disease (GVHD) and cytomegalovirus viremia when patients received further HSCT treatment. Collectively, GTX was an adjunct treatment modality for severely neutropenic patients who were likely to experience hematopoietic recovery. More randomized trials are needed to verify the efficacy and complications of GTX therapy.     

Assessing the safety of autologous stem cell transplant pathway via ambulatory care for patients with multiple myeloma

High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is the standard of care for eligible multiple myeloma (MM) patients with improved progression-free and overall survival. We reviewed the ambulatory care unit pathway for MM patients who underwent HDT/ASCT in a tertiary hospital to assess safety efficacy and outcomes. We concluded that the ambulatory care model offered for MM patients undergoing HDT/ASCT is a safe alternative pathway and highlighted further improvements.     

High-dose therapy and autologous stem cell transplantation in peripheral T-cell lymphoma: treatment outcome and prognostic factor analysis

Peripheral T-cell lymphoma (PTCL) carries a poor prognosis with conventional treatment. We retrospectively analyzed data from 45 patients with PTCL who received high-dose therapy and autologous stem cell transplantation (HDT/ASCT) from 1990 to 2008 in our center. Eighteen patients underwent HDT/ASCT in complete remission to induction chemotherapy (CR1), and 27 patients underwent HDT/ASCT in other disease statuses. The median follow-up was 113.5 months (range 52.6–261.0) for surviving patients. The 5-year overall survival (OS) and progression-free survival (PFS) were 64 and 60 %, respectively. The 5-year OS for patients in CR1 and in other disease statuses was 89 and 47 %, respectively (P = 0.002), and 5-year PFS was 83 and 43 % (P = 0.007). In the subgroup excluding anaplastic large cell lymphoma, patients transplanted in CR1 also had significantly better 5-year OS (82 vs. 37 %, P = 0.009) and PFS (82 vs. 33 %, P = 0.008) than those transplanted in other disease statuses. Multivariate analysis showed that CR1 status was the only significant prognostic factor for OS (P = 0.040) and PFS (P = 0.040). These results support the use of HDT/ASCT consolidation in CR1 for PTCL patients. Prospective randomized trials are necessary to confirm the efficacy of this approach.     

Pre-transplant positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose (FDG) predicts outcome in patients treated with high-dose chemotherapy and autologous stem cell transplantation for non-Hodgkin's lymphoma

We investigated the predictive value of sequential FDG PET before and after high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in 24 patients suffering from non-Hodgkin's lymphoma (NHL). FDG PET was performed at baseline, after three cycles of induction therapy, before and after HDT with ASCT. Response assessment from sequential PET scans using standardized uptake values (SUV) was available in 22 patients at the time of transplantation. Partial metabolic response (PMR) was defined as a >25% decrease of SUV between successive PET scans [corrected]. Six of seven patients who did not achieve a PMR after complete induction therapy developed lymphoma progression, while 10 of 15 patients with complete metabolic response (CMR) or PMR remained in continuous remission. Four of seven patients with less than PMR after induction therapy died vs two of 15 patients with CMR/PMR. Median progression-free and overall survival of patients with less than PMR after HDT and ASCT was 9 and 29 months, respectively. In contrast, neither conventional re-staging nor the International Prognostic Index were predictive. These data suggest that sequential quantitative PET imaging does enlarge the concept of chemosensitivity used to select patients with high-risk NHL for HDT and ASCT or to route them to alternative treatments.     

Norfloxacin versus cotrimoxazole for infection prophylaxis in granulocytopenic patients with acute leukemia. A prospective randomized study

Norfloxacin (NOR) or cotrimoxazole (TMP/SMX) were randomly administered to 59 granulocytopenic patients with acute leukemia for prevention of bacterial infections. Nineteen NOR patients (65%) and 22 TMP/SMX patients (73%) complained of febrile or infectious episodes during the study. The mean incidence of febrile complications per patient was higher in the TMP/SMX group: 1.05 vs 0.68 (p less than 0.05). Eleven of 16 microbiologically documented infections in the TMP/SMX group and 7 of 11 in the NOR group were caused by gram negative bacilli (GNB). NOR recipients had fewer days of fever, fewer days on parenteral antibiotics and a lower proportion of time spent febrile. Fecal surveillance cultures showed intestinal GNB colonization in 42/80 specimens in the TMP/SMX group (resistant strains: 93%) and in 8/75 specimens in the NOR group (1 resistant strain). Overall, NOR seems to be effective in eradicating GNB from the digestive tract without selection of resistant strains and in preventing febrile episodes in neutropenic patients.     

G-CSF after peripheral blood stem cell transplantation in lymphoma patients significantly accelerated neutrophil recovery and shortened time in hospital: results of a randomized BNLI trial

We have undertaken a prospective randomized study in 90 patients with relapsed or resistant lymphomas to assess the value of G-CSF (lenograstim) in the acceleration of myeloid recovery after peripheral blood stem cell transplantation (PBSCT). A common regimen of cyclophosphamide 1.5 g/m² on day 1 and lenograstim 263 μg s.c. on days 2–10 with two aphereses on days 10 and 11 was used for stem cell mobilization. 77% of patients achieved an adequate PBSC collection in two harvests (>2 × 10⁸ MNC/kg or >2 × 10⁶ CD34⁺ cells/kg). 65 patients went on to receive high-dose BEAM chemotherapy and engraftment data was available for 62. 34 patients had been randomized to receive lenograstim 263 μg/d s.c. and 28 to no growth factor. The median time to ANC > 0.5 × 10⁹/l was 9 d in the lenograstim arm versus 12.5 d in the no-lenograstim arm ( P  = 0.0001). This was associated with a median duration of time in hospital post PBSCT of 13 d in the lenograstim arm versus 15.5 d in the no-lenograstim arm ( P  = 0.0002). Median days to platelet independence, platelet transfusions, incidence of infection and red cell transfusion were the same in both arms. These data indicate that lenograstim significantly accelerated myeloid recovery after PBSCT and shortened the duration of hospital stay.     

High incidence of post‐transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib‐based regimens: a survey from the Rome Transplant Network

The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post‐engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib‐based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.     

Reduced intensity conditioning for allograft after cytoreductive autograft in metastatic breast cancer

The benefits of allografting noted in some malignant diseases might be safely extended to metastatic breast cancer by a combination of cytoreduction with high-dose chemotherapy (HDT) and autologous stem-cell transplant (ASCT) with graft-versus-tumour effect mediated by transplanted donor immune cells with nonmyeloablative allografting (reduced intensity conditioning transplantation, RICT). 17 patients with heavily pretreated disease were given tandem transplants. 13 patients sustained donor engraftment. Three had partial remission after HDT and ASCT and complete remission after RICT; they achieved full chimerism and all developed graft-versus-host disease (GVHD) before regression of cancer. Another patient did not respond to HDT and ASCT but had partial remission after RICT, giving an overall response rate of 24%. Five patients had grade II or higher acute GVHD and five had extensive chronic GVHD. No non-relapse-related deaths occurred during the first 100 days. Five patients (29%) were alive 90-2160 days (median 1320) after RICT. This two-step approach is feasible in patients with metastatic breast cancer.     

A Study of Incidence and Characteristics of Infections in 476 Patients from a Single Center Undergoing Autologous Blood Stem Cell Transplantation

Infectious complications are a major cause of morbidity and mortality in patients who undergo autologous stem cell transplantation (ASCT). We examined 476 patients with hematologic malignancies (401) or solid tumors (75) who underwent ASCT between February 1990 and May 2005. Anti-infectious prophylaxis consisted of different combinations of ciprofloxacin, cotrimoxazole, fluconazole, aerosolized amphotericin B, acyclovir, and intravenous immunoglobulins. Overall, 454 patients (95%) developed fever in the first 60 days after ASCT. In the majority of patients, initial antibiotic therapy consisted of broad-spectrum beta-lactamic with or without amikacin. A glycopeptide was administered as initial therapy in 86 cases. Overall, there were 132 (29%) clinically documented infections (37 pneumonias), 79 (17%) microbiologically documented infections (65 bacteremias), and 243 (54%) fevers of unknown origin. Coagulase-negative staphylococci (18, 25%) and E coli (18, 25%) were the organisms most frequently isolated. The pattern of infection did not change throughout the study except for a significantly higher incidence of bacteremia due to gram-positive bacteria in the first 5 years of the study. Infection-related mortality was 5% (21 cases), with pneumonia the most frequent cause of death. ASCT should be considered a low-risk procedure, although new therapeutic approaches for patients developing severe respiratory infections are still needed.