The role of stem cell mobilization regimen on lymphocyte collection yield in patients with multiple myeloma.

BACKGROUND: The lymphocyte dose (LY-DO) infused during an autograft influences absolute lymphocyte (ALC) recovery and survival following autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Factors influencing lymphocyte yield (LY-C) during leukapheresis have been poorly studied. METHODS: Factors that could influence survival, LY-C and CD34(+) cell yield were analyzed in 122 MM patients. Three mobilization regimens were used, granulocyte-colony-stimulating factor (G-CSF) alone (n=13), cyclophosphamide 1-2 g/m(2) plus G-CSF (LD-CY, n=62) and cyclophosphamide 3-4 g/m(2) and G-CSF (ID-CY, n=47). RESULTS: Using multivariate analysis, age, LY-C, ALC on day 30 (ALC-30) and International Staging System stage significantly influenced overall (OS) and progression-free survival (PFS) following ASCT. PFS (56 versus 29 months, P=0.05) and OS (72 versus 49 months; P=0.07) were longer in the LY-C>or=0.12x10(9)/kg group than the LY-C<0.12x10(9)/kg group. LY-C also influenced ALC on day 15 (ALC-15). Mobilization regimen, lymphocytes on the day of leukapheresis, prior radiotherapy and number of leukaphereses significantly influenced LY-C. Significantly higher LY-C was obtained with G-CSF alone compared with the LD-CY and ID-CY groups. CD34(+) count on the day of leukapheresis, prior chemotherapy with prednisone, cyclophosphamide, adriamycin and BCNU or melphalan, and stem cell mobilization regimen significantly influenced CD34(+) cell yield. DISCUSSION: LY-C influenced ALC-15 and survival following ASCT. Factors that influenced CD34(+) cell yield and LY-C during leukapheresis were different. Mobilization should be tailored to maximize the LY-C and CD34(+) cell yield.

A randomized comparison of empiric or pre-emptive antibiotic therapy after hematopoietic stem cell transplantation.

We performed a randomized comparison of pre-emptive and empiric antibiotic therapy for adult patients undergoing allogeneic or autologous stem cell transplantation. One hundred and fifty-three patients were randomized to receive cefepime either pre-emptively on the day that neutropenia (ANC<1.0 x 10(9) cells/l) developed irrespective of the presence of fever, or at onset of fever and neutropenia (empiric). Although there was no difference between the two arms in the proportion of patients developing fever or in the median number of days of fever, the time to onset of fever was a mean of 1 day longer in each patient on the pre-emptive arm (log rank P<0.001). The number of patients with bloodstream infections was significantly reduced in those receiving pre-emptive therapy (16/75) compared to the empiric arm (31/76) (P<0.01) but this did not translate into an appreciable clinical benefit as measured by days of hospitalization, time to engraftment, use of additional antimicrobial agents or mortality at 30 days. This study does not support the use of pre-emptive intravenous antibiotic therapy in adult stem cell transplant recipients.

A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies.

BACKGROUND: The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime. METHODS: We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety. RESULTS: For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated. CONCLUSIONS: This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.

Pamidronate reduces bone loss after allogeneic stem cell transplantation.

BACKGROUND: Rapid bone loss occurs from the proximal femur after allogeneic stem cell transplantation (alloSCT). OBJECTIVE: The objective of the study was to evaluate effects of high-dose pamidronate therapy on bone loss (BMD) after alloSCT. DESIGN: This was a randomized, multicenter, open-label, 12-month prospective study of iv pamidronate (90 mg/month) beginning before conditioning vs. no pamidronate. All 116 patients also received calcitriol (0.25 microg/d) and calcium (1000 mg/d), which were continued for another year. MAIN OUTCOME MEASURES: Primary objectives were to compare changes in BMD 12 months after alloSCT at the femoral neck, lumbar spine, and total hip between the treatment arms and assess influences of glucocorticoid and cyclosporin therapy on these changes. RESULTS: Pamidronate reduced bone loss at the spine, femoral neck, and total hip by 5.6, 7.7, and 4.9% (all P < or = 0.003), respectively, at 12 months. However, BMD of the femoral neck and total hip was still 2.8 and 3.5% lower than baseline, respectively (P < 0.05) with pamidronate. Only differences at the total hip remained significant between the two groups at 24 months. Benefits were restricted to patients receiving an average daily prednisolone dose greater than 10 mg and cyclosporin therapy for more than 5 months within the first 6 months of alloSCT. CONCLUSIONS: Pamidronate markedly reduced but did not completely prevent postallogeneic bone marrow transplantation bone loss. BMD benefits were greatest in patients on higher doses of immunosuppressive therapy, but most were lost 12 months after stopping pamidronate. Studies of more potent bisphosphonates or anabolic therapy with PTH after alloSCT are warranted with the aim of durable maintenance of bone mass.

Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen.

To assess the efficacy of recombinant human stem cell factor (rHuSCF), 48 patients who had failed to mobilize >2.0 x 10(6) CD34+ cells/kg with granulocyte colony-stimulating factor (G-CSF) (10 microg/kg twice daily) with, or without, concomitant chemotherapy (G-CSF-based regimen), were remobilized with the addition of rHuSCF (20 microg/kg/day). In all, 18/48 (38%) achieved a total of >2.0 x 10(6) CD34+ cells/kg with the second rHuSCF-based mobilisation alone and 29/48 (60%) achieved a cumulative total of >2.0 x 10(6) CD34+ cells/kg following remobilization. Inclusion of chemotherapy in the mobilization regimen resulted in a higher yield of CD34+ cells/kg for both the initial G-CSF-based and subsequent rHuSCF-based regimens (0.90 vs 0.54, P < 0.01 and 2.36 vs 1.34, P < 0.01, respectively). The total peripheral blood stem cells PBSC collected from the G-CSF-based regimen, performance status, baseline platelet count and albumin were significantly associated with successful remobilization. Patients with multiple myeloma were also more likely to successfully remobilize. There was no threshold of total collected from the failed G-CSF-based regimen below which successful remobilization with the rHuSCF-based regimen was not possible. We therefore propose a predictive model [PBSC expected = 0.6+(G-CSF-based total collection)+2 (rHuSCF-based day 1 collection)] to calculate the cumulative total of PBSC expected following a maximum of five leukaphereses. This algorithm may permit the early identification of patients who are unlikely to achieve sufficient PBSC for transplantation and allow physicians to direct the resources involved in PBSC collection in a more appropriate and economical manner.

Optimal scheduling to reduce morbidity of involved field radiotherapy with transplantation for lymphomas: a prospective Australasian Leukaemia and Lymphoma Group Study.

This study evaluated delivery of involved field radiotherapy (IFRT) with transplantation for lymphomas timed to minimise toxicity. Patients transplanted for lymphoma had infradiaphragmatic disease irradiated pre-transplant and supradiaphragmatic disease post transplant. A total of 31 patients were studied, with a median follow-up duration of 4 years. Transplant conditioning was according to clinician preference. In all, 14 patients had pre-transplant abdominopelvic IFRT and 19 had post transplant IFRT (including three who had pre-transplant IFRT). Grade III-IV haematological toxicity from pre-transplant IFRT occurred in three patients and from post transplant IFRT in 10 patients. Pre-transplant IFRT had no effect on haematological recovery post transplant, but was associated with a trend towards increased gastrointestinal toxicity (P = 0.094). Pneumonitis due to post transplant thoracic IFRT occurred in one patient. Two patients failed in involved sites after completion of protocol radiotherapy. One case of myelodysplasia has been reported. As sequenced in this study, IFRT was feasible and produced a low incidence of severe pulmonary and haematological toxicities. Patient selection, field size and radiotherapy dose warrant further study.

Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase.

We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points up to 18 months, P<0.0001. The median levels for imatinib-treated patients continued to decrease and had not reached a plateau by 24 months. A total of 24 IFN+AraC-treated patients crossed over to imatinib. Once imatinib commenced, the median BCR-ABL/BCR% levels in these patients were not significantly different to those on first-line imatinib for the equivalent number of months. The incidence of progression in imatinib-treated patients, defined by hematologic, cytogenetic or quantitative PCR criteria, was significantly higher in the patients who failed to achieve a 1 log reduction by 3 months or a 2 log reduction by 6 months, P=0.002. A total of 49 patients were screened for BCR-ABL kinase domain mutations. Mutations were detected in two imatinib-treated patients who crossed over from IFN+AraC and both lost their imatinib response. In conclusion, first-line imatinib-treated patients had profound reductions in BCR-ABL/BCR%, which significantly exceeded those of IFN+AraC-treated patients and early measurements were predictive of subsequent response.

A chronic pulmonary syndrome associated with graft-versus-host disease after allogeneic marrow transplantation.

Of 143 consecutive patients who survived at least 6 months after bone marrow transplantation (allogeneic [n = 131]; syngeneic [n = 5]; or autologous [n = 7]) and whose pulmonary function was evaluated before and on at least 2 occasions after BMT, 29 (20%) developed a chronic pulmonary syndrome without evidence for an infectious etiology. Twenty-eight (97%) presented with cough and 22 (76%) with dyspnea; abnormal chest signs were crackles in 23 (79%) and wheeze in 22 (76%). Chest roentgenogram showed pulmonary infiltrates in 15 (52%) cases but was normal in 14 (48%). All patients had major reductions in lung volumes (forced expiratory volume in 1 sec [FEV1]; relaxed vital capacity [VC]; and alveolar volume [VA]), and/or diffusing capacity (pulmonary diffusing capacity [TLCO] and single-breath carbon monoxide coefficient [KCO]). The obstructive component varied with only 18 (62%) patients developing overt airways obstruction (FEV1/VC < 75%), and in 6 of this group the fall in lung volumes preceded the onset of airways obstruction. Open lung biopsy (n = 4) showed both bronchiolitis obliterans and chronic patchy interstitial pneumonitis. The development of this syndrome was associated with acute (P < 0.001) and chronic (P < 0.0001) graft-versus-host disease of other organ systems. Twenty-four (83%) patients had a partial or complete response to immunosuppressive agents. Six (21%) have died, five (17%) of pulmonary complications. We suggest that this syndrome may be a manifestation of chronic GVHD involvement of the lung.

Comparison of helper and cytotoxic antirecipient T cell frequencies in unrelated bone marrow transplantation.

Donor/recipient histocompatibility antigen differences initiate acute graft-versus-host disease (GVHD) after bone marrow transplantation. Frequency analysis, using limiting dilution techniques, of functionally defined (helper or cytotoxic) antirecipient T lymphocyte precursors in the peripheral blood of the donor has been shown to be an accurate predictor for the development of moderate-to-severe acute GVHD. Here, we describe a sensitive assay for measuring alloreactive helper (IL-2-producing) T lymphocyte precursor (HTLp) frequencies, and compare the ability of this assay and the cytotoxic T lymphocyte precursor (CTLp) assay to detect HLA- class II and class I differences and to predict clinical outcome in a cohort of unrelated donor/recipient BMT pairs. Twenty-two pairs underwent unrelated donor BMT. Patients with high (> 1:100 x 10(3)) HTLp or CTLp frequencies had a higher incidence of moderate-to-severe (grades II-IV) acute GVHD (80% and 100%, respectively) than pairs with low (< 1:100 x 10(3)) frequencies (40% and 57%, respectively). Ten (45%) patients have died, but all patients with both a low HTLp and low CTLp frequency remain alive. The HTLp and CTLp assays provided similar predictive information for outcome. Given that the HTLp assay is more rapid and less labor intensive, it offers an additional or alternative functional method for donor selection in unrelated donor BMT.

Evidence that umbilical cord blood contains a higher frequency of HLA class II-specific alloreactive T cells than adult peripheral blood. A limiting dilution analysis.

Umbilical cord blood has been used to effect hematological reconstitution and there are sufficient stem cells available in the cord blood obtainable from a single placenta to reconstitute an adult patient. Umbilical cord blood might therefore, have widespread potential use in the field of bone marrow transplantation. We compared alloreactivity of paired samples of adult and cord peripheral blood mononuclear cells, by measuring frequencies of both alloreactive T helper cells and cytotoxic T cell precursors (CTLp), using limiting dilution analysis. In addition we compared the phenotype of adult and neonatal PBMC, using monoclonal antibody staining. Cord PBMC in general showed higher frequencies of alloreactive Th than adult PBMC, with statistically significant differences in 6 out of 10 experiments. There was no statistically significant difference between adult and cord CTLp frequencies. Adult and cord PBMC surface phenotype was similar, except that cord blood contained fewer lymphocyte function-associated-3 (LFA-3) positive (memory) cells.

The helper T lymphocyte precursor (HTLp) frequency does not predict outcome after HLA-identical sibling donor G-CSF-mobilised peripheral blood stem cell transplantation.

Here, we report the first study assessing the helper T lymphocyte precursor (HTLp) frequency as a predictor of outcome in patients undergoing allogeneic PBSC transplantation. The HTLp assay uses limiting dilution analysis to measure the frequency, in PBMCs from the donor, of T lymphocytes capable of producing IL-2 in response to histocompatibility antigenic differences on PBMCs from the recipient. This assay has shown promise as a functional histocompatibility assessment used to predict the risk of recipients of HLA-matched donor bone marrow developing severe acute GVHD: the higher the HTLp frequency, the greater the significance of any histoincompatibility, and the greater the risk of severe acute GVHD. In the current report, the HTLp frequency was measured in 28 HLA-identical sibling pairs who subsequently underwent allogeneic PBSC transplantation for haematological malignancies. The HTLp frequency did not predict for acute GVHD (P = 0.38), chronic GVHD (P = 0.95), transplant-related mortality (P = 0.79), relapse (P = 0.39) or overall survival (P = 0.84). Converting the HTLp frequency to HTLp infused per kilogram of recipient body weight also did not predict for any of the outcome measures. We conclude that, although the HTLp assay may be useful for patients undergoing BMT, it does not predict for outcome after HLA-identical sibling donor G-CSF-mobilised PBSC transplantation.

Improved detection of clinically significant host-reactive antigens prior to HLA-identical sibling peripheral blood stem cell transplantation using a dendritic cell-based helper T-lymphocyte precursor assay.

SUMMARY: Graft-versus-host disease (GVHD) due to host-reactive antigenic differences between HLA-identical pairs remains an important cause of morbidity and mortality after allogeneic transplantation. The helper T-lymphocyte precursor (HTLp) assay, using peripheral blood mononuclear cells (PBMCs), has been variably shown to detect such host-reactive differences. We assessed whether using dendritic cells (DCs) as the stimulator cells would improve the ability of the HTLp assay to detect these differences. We used PBMCs (standard HTLp assay) or monocyte-derived DCs (DC-HTLp assay) as the stimulator cells for 12 HLA-identical sibling pairs undergoing allogeneic peripheral blood stem cell transplantation. HTLp frequencies were greater by the DC-HTLp assay (median 1:77 712 vs 1:727 514; P=0.008). The standard HTLp assay did not predict for acute GVHD (P=0.42), whereas a trend was noted for the DC-HTLp assay (P=0.095). Of note, of seven patients developing moderately severe to severe acute GVHD, four had a significantly greater DC-HTLp frequency compared to the standard HTLp frequency, whereas all four patients who developed no to moderate acute GVHD had similar HTLp frequencies whether PBMCs or DCs were used as the stimulator cells. Although the small number of donor/recipient pairs assessed limits the strength of any conclusions, our study suggests that the DC-HTLp assay is better able to detect clinically significant host-reactive antigenic differences between HLA-identical siblings.

Hyperbaric oxygen in the treatment of refractory haemorrhagic cystitis.

Haemorrhagic cystitis is a common and often debilitating complication of chemotherapy for which treatment is frequently unsatisfactory. With over 80 cases reported of radiation-induced cystitis treated successfully with hyperbaric oxygen, attention is now turning to the treatment of chemotherapeutic agent-induced cystitis. We report a case of haemorrhagic cystitis occurring after autologous peripheral blood stem cell transplantation for multiple myeloma. The patient had received cyclophosphamide and busulfan and had BK and adenoviruria. The haemorrhage was refractory to multiple conventional treatments but resolved after a course of hyperbaric oxygen.

Chronic airflow obstruction in long-term survivors of allogeneic bone marrow transplantation.

Prospective pulmonary function tests (PFTs) of 49 long-term survivors of identical sibling bone marrow transplants (BMT) were analysed. Eight (16%) developed a persistent pulmonary syndrome characterised by a late onset, cough and dyspnoea, hyperinflation or patchy infiltrates on plain radiography and episodic bacterial infections. The predominant PFT pattern was obstructive (reduced forced expiratory ratio, FER) with a variable restrictive component (reduced vital capacity, VC). When compared with the other 41 patients (controls), mean FER (53% absolute) and VC (73% predicted) were significantly lower at 12 months (P = 0.005). Graft-versus-host disease (GVHD) was the only identifiable risk factor (odds ration 7.1). Five of 7 patients compared with 4 of 31 controls tested at 3 months had an abnormal FER or maximum mid-expiratory flow rate (MMFR), but not VC, prior to the onset of symptoms (P = 0.015). Patients with mild to moderate disease (FER 50-70%) had stable pulmonary function while severe cases progressed despite immunosuppressive agents. Earlier recognition of this syndrome by a reduced FER or MMFR may allow the initiation of therapy at a potentially reversible stage.

Abnormal cervical cytology in bone marrow transplant recipients.

Particular human papillomavirus (HPV) subtypes are implicated in the genesis of abnormal cervical cytology and cervical cancer. While most immunocompetent hosts clear HPV infection with no sequelae, some develop premalignant cytological changes of whom a minority subsequently progress to overt carcinoma. Immunocompromised patients, such as renal allograft recipients and HIV-infected individuals, have a higher rate of cytological abnormalities. This is thought to be due to prolonged persistence of virus due to impaired clearance by the immune system. We undertook a retrospective review of the cervical cytology of all women who underwent BMT at two transplant centres and who had cervical smears performed between 1990 and 1998. The rate of cytological abnormalities was significantly higher than in the general population before BMT (age-adjusted odds ratio (OR) 2.2, P = 0.02) and after BMT (OR 7.0, P < 0.0001). After BMT, allogeneic recipients had a higher rate of abnormalities than did autologous patients (OR 2.6, P = 0.02) although only allogeneic recipients had a higher rate of abnormalities post-BMT compared to pre-BMT (allogeneic OR 6.8, P = 0.004). These observations suggest that pre-transplant disease and treatment factors increase the risk of cytologic abnormalities and that transplant-related factors such as conditioning therapy and immunosuppression further increase this risk. These data suggest that more frequent screening may be required in these at-risk groups, especially allogeneic recipients. Prospective studies are required to further evaluate cytological abnormalities and HPV shedding in these populations.

Acute pancreatitis complicating a bone marrow harvest.

A patient developing acute pancreatitis with pseudocyst formation after an uncomplicated bone marrow harvest is reported. The diagnosis was confirmed by elevated serum amylase and lipase, and by CT scan. We suggest that the pancreatitis may have been precipitated by spasm of the sphincter of Oddi secondary to opiates administered as premedication and for pain relief.

Cytomegalovirus viral load monitoring after allogeneic bone marrow transplantation in patients receiving antiviral prophylaxis.

Cytomegalovirus viral load measurement is a powerful new tool for monitoring of CMV disease; however, the optimal strategy for use is unknown. Weekly plasma CMV viral loads and CMV-related outcomes were monitored in 46 consecutive allogeneic bone marrow transplantation (BMT) recipients receiving standardised antiviral prophylaxis. A total of 412 CMV viral loads were quantitated in the first 100 days post transplantation with 77 positive samples (19%) in 20 patients (43%). No patient with all negative CMV viral load results developed CMV disease. Two of three patients with highly positive CMV viral loads (first positive < or =30 days post transplant, maximum viral load > or =5000 copies/ml, and > or =50% of samples positive) developed CMV disease. A total of 17 patients with positive CMV viral loads, who did not meet the criteria for highly positive, did not develop CMV disease. CMV viral load detection was higher in recipients who were CMV sero-positive. In conclusion, CMV disease did not occur in the setting of a persistently negative CMV viral load. A positive CMV viral load result occurred commonly after allogeneic BMT, even in patients receiving antiviral prophylaxis.

Allogeneic haemopoietic cell transplants in Australia, 1996--a multi-centre retrospective comparison of the use of peripheral blood stem cells with bone marrow.

A retrospective comparison was carried out on adult patients receiving HLA-identical allogeneic haemopoietic stem cell transplants from siblings in Australia in 1996, comparing bone marrow with G-CSF-mobilised peripheral blood stem cells. A total of 131 transplant recipients from nine centres were included in this study, of whom 79 received bone marrow, 44 blood stem cells and eight both. All but three of the 131 patients had cyclosporin and methotrexate as graft-versus-host disease prophylaxis. The minimum follow-up time for surviving patients is 27 months. Comparisons were carried out between the BM and PBSC groups. There were no significant differences between groups in age, sex, diagnosis, donor characteristics or pretransplant conditioning. Median time to neutrophil recovery of 0.5 x 10(9)/l was 14 days for PBSC recipients, compared to 19 days for marrow recipients (P < 0.0005). median time to platelet recovery of 20 x 10(9)/l was 17 days for PBSC recipients, compared to 28 days for marrow recipients (P < 0.0005). there were no significantly increased risks of either acute or chronic GVHD in the PBSC recipients. there were no significant differences between the groups in the incidence of major transplant-related complications, disease-free survival or overall survival.

Matched unrelated donor bone marrow transplantation for chronic myeloid leukaemia in chronic phase: comparison of ex vivo and in vivo T-cell depletion.

Between January 1985 and March 1992, 48 patients with chronic phase CML underwent BMT from volunteer unrelated donors (MUD) serologically identical at HLA-A, B and DR loci. 19 patients received donor marrow ex vivo T-cell depleted (EX-TCD) with Campath monoclonal antibodies. 29 patients received unmanipulated donor marrow with CsA/MTX GVHD prophylaxis; 28 received additional intravenous antilymphocyte therapy from day +1 to +5 (IN-TCD). Overall 26 patients survive at median follow up of 362 days; actuarial survival at 3 years is 50%. 3 patients have sustained haematological relapse; actuarial leukaemia-free survival is 38%. There is no difference in overall survival between the EX-TCD and IN-TCD groups, but primary graft failure (n = 4) occurred only in the EX-TCD group, while GVHD (grade II or greater) occurred more frequently in the IN-TCD group (61% vs. 29%, p = 0.084). The optimum method for GVHD prophylaxis in MUD BMT remains uncertain.

Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim.

This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34(+) yield 0.5-1.9 x 10(6)/kg BW) with filgrastim-alone or chemotherapy-plus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n=13), rHuSCF 20 microg/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n=31), rHuSCF 20 microg/kg/day plus filgrastim 5-10 microg/kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of >or=3 x 10(6) CD34(+) cells/kg. In both groups, CD34(+) yield (x 10(6)/kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P=0.002 and 1.64 vs 0.99 P=<0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 x 10(6)/kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 x 10(6)/kg BW in the prior mobilization as in those with 0.76-1.99 x 10(6)/kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34(+) cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.