Randomized trial of peripheral blood progenitor cell vs bone marrow as hematopoietic support for high-dose chemotherapy in patients with non-Hodgkin's lymphoma and Hodgkin's disease: a clinical and molecular analysis.

Filgrastim (r-metHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) and unstimulated bone marrow (BM) were evaluated and compared for reconstitution after high-dose chemotherapy in patients with relapsed Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) with respect to engraftment, overall and relapse-free survival, and contamination by lymphoma cells using molecular analysis of immunoglobulin gene rearrangements. Forty-four patients with either NHL or HD underwent autologous transplantation after high-dose chemotherapy. Patients were randomized to receive either Filgrastim-mobilized PBPC (n = 15) or unstimulated BM (n = 14). An additional 15 patients received PBPC without randomization because of a recent history of marrow involvement by lymphoma. Use of PBPC was associated with faster neutrophil engraftment than BM (11 vs 14 days to an absolute neutrophil count >0.5 x 10(9)/l, P = 0.04), but without any difference in platelet engraftment, infectious complications, or overall or event-free survival. Both BM (65%) and PBPC (73%) were frequently contaminated by tumor cells as assessed by CDR3 analysis. Patients with negative polymerase chain reaction analysis of a BM sample during the study had a trend towards an improved survival; however, BM involvement by disease had no impact on the ability to mobilize or collect PBPC. We conclude that PBPC are as effective as BM in reconstituting hematopoiesis after high-dose chemotherapy and that both products are frequently contaminated by sequences marking the malignant clone.     

Philadelphia chromosome-positive secondary acute myeloid leukemia following high-dose chemotherapy with peripheral blood progenitor cell support for relapsed low-grade non-Hodgkin's lymphoma

 We report the case of a 47-year-old patient who developed acute myelogenous leukemia (AML) 18 months after receiving high-dose chemotherapy with peripheral blood progenitor cell support (PBPCT) for relapsed low-grade follicular non-Hodgkin's lymphoma (NHL). Cytogenetic analysis of the leukemic cells showed the translocation (9;22)(q34;q11). In three mitoses, an addiditional Philadelphia chromosome (Ph¹) was present. In the literature, Philadelphia chromosome-positive secondary AML has been described only once before in a patient with multiple myeloma. Received: 7 August 1996 / Accepted: 23 September 1996     

Tandem transplant of peripheral blood stem cells for patients with poor-prognosis Hodgkins's disease or non-Hodgkin's lymphoma.

To improve the results of high-dose therapy with autologous stem cell transplantation, new conditioning regimens with acceptable toxicity must be developed. The aim of this study was to evaluate the feasibility and toxicity of two myeloablative regimens performed at a 2-month interval. After salvage chemotherapy and collection of peripheral stem cell progenitors (median CD34+ cells/kg: 11 x 106/kg), (n = 15) patients with aggressive non-Hodgkin's lymphoma with poor prognostic factors or refractory Hodgkin's disease (n= 9) received intensified regimens. The first conditioning regimen, consisting of BCNU-cyclophosphamide-VP16-mitoxantrone was followed by transplantation of a median number of 4 x 10(6) CD34+ cells/kg; then, after a median interval of 56 days, a second preparative regimen, combining busulfan-aracytine-melphalan or TBI + aracytine-melphalan, was followed by transplantation of a median of 4 x 10(6) CD34+ cells/kg. After regimens 1 and 2, respectively: median time to neutrophil recovery >500/microl was 11 days (both times); median time to platelet counts >50,000/microl was 14 and 36 days, but values > 20,000/microl were reached by days 13 and 16 (P = 0.9); mucositis grade III-IV was observed in 11 and 15 cases. The median number of days with fever >38 degrees C was significantly higher (7.8 days) after the second transplant (P <0.05). Three cases of veno-occlusive disease (VOD) were observed after the second transplant. At a median follow-up of 18 months, 14/24 (58%) patients remained in CR, seven patients had died (two of VOD and five after relapse) and two were alive in relapse. These results indicate that tandem transplants performed at a 2-month interval in poor risk lymphoma can be used with acceptable hematotoxicity. VOD remains the major drawback and hepatotoxic drugs, such as busulfan, should be used with caution. Longer term follow-up of a larger cohort of patients is needed to ascertain the overall efficacy.     

Effect of high-dose chemotherapy in patients with relapsing or resistant Hodgkin's disease

The authors evaluated a group of 48 patients with relapsing or resistant Hodgkin's disease. The patients were treated by life-saving chemotherapy followed by large doses of chemotherapy and autologous transplantation of haematopoietic cells. For life-saving chemotherapy they used most frequently a combination of VIM in 40 patients and combinations of DHAP, MINE, MiniDexaBEAM. In 11 patients they changed the regime of life-saving chemotherapy because of a poor response. After completed life-saving chemotherapy 18 (37.5%) patients were in CR, 27 (56.2%) in PR and in 3 (6.3%) the disease progressed. For large dose chemotherapy the authors used BEAM in 32 patients, CBV in 2, Busulfan with Cyclophosphamide in 13 patients and Busulfan with Melfalan in one patient. After completion of large dose chemotherapy and subsequent autologous transplantation of bone marrow 31 (64.6%) patients were in CR, 8 (16.7%) in PR and the disease progressed in 9 (18.7%). In August 1999 a total of 44.9% patients in CR survive, the median period of follow up after autologous transplantation was 23 months. Life-saving chemotherapy with subsequent large dose chemotherapy led in the investigated group to induction of CR in 64.6% patients which is the basic prerequisite of long-term survival.     

Characteristics of blood cells during peripheral blood stem cell mobilization following chemotherapy in patients with non-Hodgkin's lymphoma

The objective of our study was to obtain a predictor of the timing for peripheral blood stem cell (PBSC) collection using routine blood cell counts. For that purpose, we compared recovery kinetics of peripheral blood cells and CD34+ cells in non-Hodgkin's lymphoma patients who were given granulocyte-colony stimulating factor for PBSC collection after CHOP therapy. Peaks in the monocyte/WBC ratio and reticulocyte high fluorescence ratio (HFR) were observed 2 to 3 days prior to the peak CD34+ cell count. In addition, the appearance of immature granulocytes in peripheral blood correlated well with increases in CD34+ PBSC number. These findings suggested the peak monocyte/WBC ratio, HFR, and immature granulocyte count can be used as predictors of the timing for PBSC harvests.     

VACOP-B, high-dose cyclophosphamide and high-dose therapy with peripheral blood progenitor cell rescue for aggressive non-Hodgkin's lymphoma with bone marrow involvement: a study by the non-Hodgkin's Lymphoma Co-operative Study Group

BACKGROUND AND OBJECTIVE: Sequential treatment with the addition of high-dose therapy (HDT) and peripheral blood progenitor cell (PBPC) rescue has been reported to be active as front-line therapy in aggressive non-Hodgkin's lymphoma (NHL) with bone marrow (BM) involvement. We designed an intensive sequential therapy as front-line therapy in this subset of patients and conducted a phase II study. DESIGN AND METHODS: Patients with aggressive non-Hodgkin's lymphoma and BM involvement at diagnosis received 8 weeks of VACOP-B chemotherapy as induction therapy. The second phase included high-dose cyclophosphamide (HDCY) (7 g/m(2)) with granulocyte colony-stimulating factor (G-CSF) followed by leukaphereses. The third phase included HDT according to the BEAM protocol or melphalan (140 mg/m(2)) plus total body irradiation (8 Gy in a single dose). RESULTS: Forty patients were included in the study. According to the intention-to-treat, after VACOP-B, 11 (27.5%) and 22 (55%) patients achieved complete remission (CR) and partial remission (PR), respectively. Thirty-four received HDCY. After HDCY, 18 patients (45%) were in CR and 13 (32.5%) in PR. Twenty-nine underwent HDT plus peripheral blood cell rescue (PBPC) rescue. At the completion of treatment 29 patients (72.5%) were in CR, and 3 patients (7.5%) in PR. The actuarial 3-year overall survival, disease free survival and failure free survival are 48%, 55% and 40%, respectively. Overall severe toxicity was 7.5%. INTERPRETATION AND CONCLUSIONS: This phase II study suggests that the intensified treatment described is feasible and active in aggressive NHL with BM involvement. A randomized trial is now underway to test this approach.     

Feasibility of peripheral blood progenitor cell mobilization and harvest to support chemotherapy intensification in elderly patients with poor prognosis: non-Hodgkin's lymphoma

Mobilized peripheral blood progenitor cells (PBPC) are widely employed in the management of adult patients with high-risk non-Hodgkin's lymphoma (NHL), though their use in the elderly has received little attention. This study was mounted to assess the feasibility of the mobilization, harvesting, and reinfusion of PBPC in NHL patients aged >60. Twenty patients (median age: 67, range: 61-80) with poor-prognosis NHL entered the pilot study: nine others were discarded for various reasons. Thus, the program was applicable to 69% of potential candidates. Fourteen patients were at onset and six were being treated for refractory disease or relapses. Mobilization was induced with cyclophosphamide 4 g/m(2), followed by 5 micro g/kg per day granulocyte-colony stimulating factor (G-CSF) s.c. until PBPC collection or hemopoietic recovery. Sixteen patients (80%) displayed some signs of mobilization (CD34+: >5/ micro l). Maximum mobilization varied with median circulating CD34+ cells and colony forming units-granulocyte/macrophage (CFU-GM) peaks of 17.2/ micro l (range: 8.1-210) and 1,650/ml (range: 540-62,900), respectively. A median of two leukaphereses resulted in the harvesting of a median of 6.7x10(6) (range: 0.3-33.6) CD34+/kg and 21.1x10(4) (range: 1.2-209) CFU-GM/kg. Intensified therapy with intermediate-dose melphalan, associated or not with mitoxantrone, was delivered with autologous PBPC support to 13 patients and always resulted in rapid and stable hemopoietic reconstitution. The program was well tolerated and no treatment-related deaths occurred. Twelve patients are still alive with a 5-year survival projection of 59%. In conclusion, the results demonstrate the feasibility of using autologous PBPC to support therapy intensification even in elderly patients.     

Evaluation of acute toxicities associated with autologous peripheral blood progenitor cell reinfusion in patients undergoing high-dose chemotherapy

Peripheral blood progenitor cell reinfusion (PBPC) in patients undergoing high-dose chemotherapy (HDC) for poor prognosis malignancies, has been described as causing possible acute gastrointestinal (nausea, vomiting), allergic (oedema, bronchospasm, anaphyl- axis), renal (proteinuria, haematuria) and/or cardiovascular (hypotension, arrhythmia, conduction disturbances, transient ischaemic phenomena) toxicities. To establish the clinical relevance of these observations and the possible relationship with different HDC regimens used, we performed a clinical and instrumental evaluation on 33 patients with advanced breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, relapsed ovarian cancer, Ewing's sarcoma, extragonadal germinal tumour and small cell lung cancer. They underwent at least one reinfusion each for a total of 51 studied procedures. No patient had a previous history of cardiovascular disease or significant intercurrent illness such as diabetes or liver, renal or neurologic impairment. All patients had totally implanted central venous catheters, through which the transplants had been collected and reinfused without technical consequences. To evaluate cardiovascular function, we continuously monitored 12-lead ECGs, with arterial pressure (AP) measurements every 5 min from the beginning of the procedure to 15 min after the reinfusion ended. We did not observe any significant differences between basal and subsequent steps in AP, heart rate, PQ and QTc time, P wave and QRS complex duration or P wave and QRS electrical axes. No patient showed any ST-T tract pathological abnormality, but one patient developed a transient ectopic atrial rhythm, without any haemodynamic disfunction and with spontaneous reversion to sinus rhythm. No patient complained of symptoms of haemodynamic failure. Gastrointestinal side-effects appeared to be strictly related to speed of reinfusion and to the number of packs reinfused, probably reflecting on the amount of dimethylsulphoxide infused. In one patient a tonic-clonic seizure occurred during a vomiting episode, but no patient developed allergic or renal toxicities. We conclude that PBPC reinfusion, if managed according to the procedure we propose in patients without organic impairment, is a safe procedure not associated either with increased risk of acute arrhythmias or ischaemic or significant systemic acute toxicities. Bone Marrow Transplantation (2000) 25, 173-177.     

Molecular analysis of patients with relapsed or refractory intermediate-high grade non-Hodgkin's lymphoma with bone marrow infiltration undergoing peripheral blood progenitor cell transplantation.

BACKGROUND AND OBJECTIVES: IgH gene rearrangement studies with a polymerase chain reaction (PCR) technique can detect the persistence of clonal cells at molecular level during the remission phase. This persistence of clonal cells can be used to establish the relationship between minimal residual disease (MRD) and clinical outcome. We have developed a three-step single strand conformational polymorphism PCR strategy which is able to detect clonal B lymphoid cells at a frequency as low as 1 clonal cell in 10(6) normal cells. DESIGN AND METHODS: Twenty patients with intermediate or high-grade B non-Hodgkin's lymphoma (NHL) were evaluated. Patients were pre-treated with a median of two (range 1-4) conventional chemotherapy lines before high-dose cyclophosphamide (HDCY). All patients had their bone marrow (BM) involved by disease (median 10%; range 5-50%). Nineteen patients were offered high-dose therapy followed by peripheral blood progenitor cells (PBPC) autografting. RESULTS: MRD analysis was performed for each patient at the end of conventional chemotherapy and every three months after high dose therapy. All these patients achieved complete response (CR) after high dose therapy (HDT). Six patients relapsed after a median time of 24.5 months. All the studied apheresis samples were positive at the molecular analysis. All 6 patients still positive at the molecular analysis after PBPC autografting relapsed. The remaining 13 patients who were negative maintained CR. INTERPRETATION AND CONCLUSIONS: Whereas the detection of clonal cells in the apheresis samples did not predict an unfavorable outcome, the disappearance of the clonal rearranged band from the BM sample after HDT proved to be a favorable prognostic factor and was associated with long-lasting disease-free status     

Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation

The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.     

Circulating CD20 and CD52 in patients with non-Hodgkin's lymphoma or Hodgkin's disease

The cell surface proteins CD20 and CD52 differ significantly in their structures and are expressed on the majority of B cells. Both circulating CD20 (cCD20) and circulating CD52 (cCD52) have been recently documented in patients with chronic lymphocytic leukaemia. A retrospective study to establish whether cCD20 and/or cCD52 were detectable in patients with lymphoma, and the clinical associations of these soluble antigens if detected, was conducted. cCD20 and cCD52 levels were analysed in a cohort of 65 patients with non-Hodgkin's lymphoma (NHL) and 37 with Hodgkin's disease (HD). Patients with NHL had elevated pretherapy levels of cCD20 and cCD52 compared with normal individuals. Patients with HD had significantly lower than normal pretherapy levels of both cCD20 and cCD52. cCD20 levels were marginally elevated post-therapy in NHL patients while in patients with HD, cCD20 levels remained significantly lower than normal after therapy. Serum cCD52 levels became significantly lower than normal post-therapy in NHL patients, and remained significantly lower than normal in HD patients. No predictive effects were found for pretherapy or post-therapy levels of cCD52 on survival for either cohort of patients. Post-therapy cCD20 levels independently highly correlated with survival in patients with NHL. Prospective evaluation will be required to establish if cCD20 and cCD52 may be used as biomarkers in the diagnosis, prognostic categorization, and monitoring of the clinical course in patients with lymphoma. The clinical significance of circulating antigen in patients receiving monoclonal antibody therapy directed against CD20 and/or CD52 warrants study.     

Intensification of salvage treatment with high-dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma

The aim of the present study was to retrospectively evaluate whether a high-dose sequential chemotherapy programme (HDS: cyclophosphamide, methotrexate, etoposide) administered prior to autologous transplantation could optimize the salvage of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma. Between 1985 and 1999, 103 patients (median age 43 years, range 16-65) from eight Italian centres and one Swiss centre, with refractory (n = 38) or relapsed (n = 65) diffuse large B-cell and T-cell lymphoma, were treated using HDS followed by high-dose regimens with autologous haematopoietic stem cell transplantation. Eighty-three patients responded to the HDS regimen (81%, 95% C.I., 73- 88%) and 79 eventually achieved a complete response (CR) after autotransplantation (90%, 95% C.I., 81- 96%). None of 20 cases resistant to HDS attained CR. Treatment-related mortality was 4%. After a median follow-up of 24 months (range 6-174 months), 3-year estimates of overall survival, event-free survival and disease-free survival were 47% (95% C.I., 36-59%), 44% (95% C.I., 34-54%) and 64% (95% C.I., 50-74%) respectively. Multivariate analysis showed that chemosensitivity to HDS represented the strongest predictor of both CR and survival. This retrospective study shows that salvage treatment using HDS had relatively low toxicity and was associated with remarkable response rates, allowing further effective therapy with high-dose autograft programmes.     

Successful treatment of advanced natural killer cell lymphoma with high-dose chemotherapy and syngeneic peripheral blood stem cell transplantation.

CD56+ angiocentric lymphoma has currently been recognized as a distinct clinical entity which is the prototype of the putative NK cell lymphomas. A 16-year-old Japanese girl with advanced CD56+ angiocentric lymphoma received high-dose chemotherapy supported with syngeneic peripheral blood stem cell transplantation (PBSCT). Prior to syngeneic PBSCT, she received six cycles of conventional chemotherapy before transplantation, resulting in a partial response. PBSC were mobilized with granulocyte colony-stimulating factor (G-CSF) and collected from her identical twin. High-dose cyclophosphamide, MCNU, etoposide, and carboplatin were used for pretransplant conditioning. Syngeneic PBSCT was well tolerated. She achieved complete remission and is now surviving in continuous complete remission for more than 30 months after syngeneic PBSCT. Thus, marrow-ablative chemotherapy facilitated by autologous or allogeneic PBSCT should be considered as part of the primary therapy for poor prognosis NK cell lymphomas.     

Sequential peripheral blood progenitor cell transplantation after mobilization with salvage chemotherapy and G-CSF in patients with resistant lymphoma

We enrolled 18 patients affected by refractory or relapsed lymphoma (HD, NHL) in a two-step protocol that included salvage chemotherapy with mitoxantrone, carboplatinum, methylprednisolone, and cytosine arabinoside (MICMA) plus G-CSF (5 μg/kg/day), peripheral blood progenitor cell (PBPC) collection, and subsequent transplantation after BUCY2 regimen. After MiCMA chemotherapy, four patients (22%) achieved complete response, eight patients (44%) obtained a partial response, and six showed progression of disease (PD). Fourteen out of 18 patients (78%) were considered eligible for PBPC transplantation. Three patients with complete response refused PBPCT; they are currently in continuous complete remission (CCR) at 15, 13, and 15 months, respectively. One patient has been recently transplanted but is too early to be evaluated. Ten patients so far completed the study, eight of whom are currently alive in CR, with a median follow-up of 7.5 months (range 2–13). Hematologic reconstitution was very rapid with a median time to achieve WBC > 1 × 10⁹/L, PMN > 0.5 × 10⁹/L, platelets > 50 × 10⁹ /L and > 100 × 10⁹/L of 13 (range 9–15), 12(range 9–14), 10(range 0–22), and 14 (range 5–49) days, respectively. Our protocol is highly effective as a salvage treatment, while permitting PBPC collection after G-CSF administration. Hemopoietic reconstitution after transplantation of PBPCs collected with this procedure is complete, rapid, and sustained. © 1994 Wiley-Liss, Inc.     

ESHAP plus G-CSF as an effective peripheral blood progenitor cell mobilization regimen in pretreated non-Hodgkin's lymphoma: comparison with high-dose cyclophosphamide plus G-CSF

The ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) regimen has been shown to be effective as an active salvage therapy for lymphoma. Mobilizing stem cells following ESHAP should decrease time to transplantation by making separate mobilizing chemotherapy (MC) unnecessary, while controlling a patient's lymphoma. We therefore assessed the mobilization potential of ESHAP plus G-CSF in 26 patients (ESHAP group) with non-Hodgkin's lymphoma (NHL) and compared these results with those of 24 patients with NHL who received high-dose (4 g/m2l) cyclophosphamide (HDCY) as MC (HDCY group). The age, sex, and radiotherapy to the axial skeleton were well matched between groups, but the number of patients with poor mobilization predictors was higher in the ESHAP group. Significantly higher numbers of CD34+ cells (x 10(6)/kg) (17.1+/-18.8 vs 5.8+/-5.0, P=0.03) and apheresis day 1 CD34+ cells (x 10(6)/kg) (5.5+/-6.6 vs 1.7+/-2.0, P=0.014) were collected from the ESHAP group than from the HDCY group, and the number of patients who achieved an optimal CD34+ cell target of 5 x 10(6)/kg was higher in the ESHAP group (81 vs 50%, P=0.022). Log-rank test revealed that time to target peripheral blood progenitor cell collection (> or =5 x 10(6)/kg) was shorter in the ESHAP group (P=0.007). These results indicate that ESHAP plus G-CSF is an excellent mobilization regimen in patients with relapsed and poor-risk aggressive NHL.     

Treatment outcome and prognostic factors for relapse after high-dose chemotherapy and peripheral blood stem cell rescue for patients with poor risk high grade non-Hodgkin's lymphoma.

The aim of the study was to determine treatment outcome and identify a particularly high risk group in a consecutive series of 66 patients with poor prognosis high grade lymphoma (NHL) treated with conventional induction chemotherapy followed by high-dose chemotherapy (HDCT) and peripheral blood stem cells (PBSC) rescue. Fifty-one patients with intermediate grade NHL (Kiel) and two or three adverse prognostic features as defined by the age-adjusted International Prognostic Index (IPI) received induction treatment with 7 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone and methotrexate (VAPEC-B) followed by three cycles of ifosfamide/cytarabine. Fifteen patients with high grade Burkitt's and lymphoblastic NHL received 11 weeks of VAPEC-B followed by three cycles of high-dose methotrexate. HDCT for all 66 patients consisted of busulphan/cyclophosphamide followed by autologous PBSC rescue. Thirty-one patients (47%) received HDCT in first complete remission (CR/CRu) and 34 patients (52%) in first partial remission (PR) after conventional chemotherapy. Following HDCT, 42 patients (64%) were in CR/CRu, 19 patients (29%) in PR and one patient had progressive disease. There were four toxic deaths. After a median follow-up period of 27 months (range 7-73) in 46 surviving patients, the actuarial 3-year estimates of overall survival, event-free survival (EFS) and freedom from progression (FFP) were 67%, 65% and 70%, respectively. In univariate analysis, prognostic factors associated with reduced EFS were mediastinal bulk (P = 0.02), > or = 3 extra-nodal sites (P = 0.02), remission status prior to HDCT (P = 0.05), low albumin (P = 0.08) and raised ESR (P = 0.09). No significant difference was observed between patients with intermediate or high grade NHL or between patients with two or three adverse IPI features. Multivariate analysis identified mediastinal bulk (P = 0.01), > or = 3 extra-nodal sites (P = 0.01) and low albumin (P = 0.03) as joint predictors of poor EFS. Remission status prior to HDCT was not found to be significantly associated with reduced EFS, FFP or survival, suggesting early introduction of HDCT may benefit patients with a PR. Based on these three adverse features, three groups (0, 1 or > or = 2 features) could be identified with differing EFS, survival and freedom from progression (FFP) rates at 3 years; 85%, 63% and 20%, respectively for EFS, 84%, 64% and 25% for survival and 85%, 66% and 33%, respectively for FFP. This prognostic model may identify patients with a particularly poor prognosis despite HDCT, who may benefit from other therapeutic approaches.     

Mobilization of peripheral blood stem cells with high-dose cyclophosphamide or the DHAP regimen plus G-CSF in non-Hodgkin's lymphoma

Our study analyzes the mobilization of hematopoietic stem cells after two chemotherapeutic regimens in non-Hodgkin's lymphoma (NHL) patients. The study included 72 patients with NHL (42 follicular and 30 large cells). The mean age was 37 years (range 17-60). Sixty-four patients (88.9%) had stage III-IV disease. Forty-eight patients (66.7%) had bone marrow involvement. Systemic B symptoms were present in 42 patients (58.3%). Mobilization chemotherapy regimens were randomly assigned as DHAP in 38 patients (52.7%) or cyclophosphamide (CPM) (5 g/m(2)) in 34 (47.2%) and the results of 132 procedures were analyzed. At the time of PBSC mobilization, 46 patients (63.9%) were considered to be responsive (complete remission, partial remission or sensitive relapse) and 26 (36.1%) not responsive (refractory relapse or refractory to therapy). Pre-apheresis CD34+ blood cell count and number of previous chemotherapy treatments were used to predict the total number of CD34+ cells in the apheresis product. The mobilizing regimens (CPM or DHAP) were similar in achieving the threshold CD34+ cell yield, for optimal engraftment. Since DHAP was very effective as salvage treatment, we suggest using DHAP as a mobilizing regimen in patients with active residual lymphoma at the time of stem cell collection.