Comparison of filgrastim, pegfilgrastim, and lipegfilgrastim added to chemotherapy for mobilization of CD34+ cells in non-Hodgkin lymphoma patients.

BACKGROUND: Data are limited on the long-acting granulocyte-colony stimulating factors (G-CSFs) pegfilgrastim (PEG) and lipegfilgrastim (LIPEG) compared with filgrastim (FIL) regarding the mobilization efficiency of CD34+ cells, graft cellular composition, and engraftment. STUDY DESIGN AND METHODS: In this prospective nonrandomized study, 36 patients with non-Hodgkin lymphoma received FIL, 67 received PEG, and 16 patients received LIPEG as a cytokine after chemotherapy. We analyzed the mobilization and collection of CD34+ cells, cellular composition of blood grafts, and hematologic recovery after auto-SCT according to the type of G-CSF used. RESULTS: Patients in the LIPEG group had fewer apheresis sessions (1 vs. 2, p = 0.021 for FIL and p = 0.111 for PEG) as well as higher median blood CD34+ cell counts at the start of the first apheresis (LIPEG 74 × 106 /L vs. FIL 31 × 106 /L, p = 0.084 or PEG 27 × 106 /L, p = 0.021) and CD34+ yields of the first apheresis (FIL 5.1 × 106 /kg vs. FIL 2.3 × 106 /kg, p = 0.105 or PEG 1.8 × 106 /kg, p = 0.012). Also, the costs associated with G-CSF mobilization and apheresis were lower in the LIPEG group. The graft composition was comparable except for the higher infused CD34+ cell counts in the LIPEG group. The engraftment kinetics were significantly slower in the FIL group. CONCLUSION: LIPEG appears to be more efficient compared with PEG after chemotherapy to mobilize CD34+ cells for auto-SCT demonstrated as fewer sessions of aphereses needed as well as 2.8-fold CD34+ cell yields on the first apheresis day. Early hematologic recovery was more rapid in the LIPEG group. Thus further studies on LIPEG in the mobilization setting are warranted.

High-dose thiotepa-based chemotherapy with autologous stem cell support in elderly patients with primary central nervous system lymphoma: a European retrospective study.

In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT. Fifteen patients (28.8%) received HDT-ASCT as first-line treatment and 37 (71.2%) received it as second or subsequent line. Remission status before HDT-ASCT was: CR 34.6%, PR 51.9%, stable disease 3.8% and progressive disease 9.6%. Following completion of HDT-ASCT, 36 patients (69.2%) achieved CR (21.2% first-line setting and 48.1% second or subsequent line setting) and 9 (17.3%) PR (5.8% first-line setting and 11.5% second or subsequent line setting). With a median follow-up of 22 months after HDT-ASCT, median PFS and OS were reached after 51.1 and 122.3 months, respectively. The 2-year PFS and OS rates were 62.0% and 70.8%, respectively. We observed two HDT-ASCT-associated deaths (3.8%). In selected elderly PCNSL patients, HDT-ASCT, using thiotepa-based conditioning regimes, is feasible and effective. Further prospective and comparative studies are warranted to further evaluate the role of HDT-ASCT in elderly PCNSL patients.

Conflicting HLA assignment by three different typing methods due to the apparent loss of heterozygosity in the MHC region.

Loss of heterozygosity (LOH) has been reported to cause false human leukocyte antigen (HLA) homozygous typing results in pre-transplant patients suffering from haematological malignancies, who in fact are HLA heterozygous. This poses a challenge for histocompatibility testing, as a stem cell graft from a genuinely HLA homozygous donor to a mistyped patient may lead to acute life-threatening graft-vs-host disease. LOH in the HLA region on chromosome 6 is known to be quite common in solid tumours, helping malignant cells to escape T-cell surveillance, but the incidence in haematological malignancies is less well known and the estimates vary. Here we report LOH in the HLA region of five patients with haematological malignancy. We found considerable differences in sensitivity between the three different HLA typing methods used in our laboratory: SSP was clearly the most sensitive method for detecting the lost haplotype, followed by rSSO, while SBT was the least sensitive technique. A subsequent, retrospective genotyping of 65 HLA homozygous haematological patients by SSP method showed no mistyped LOH cases in our laboratory in the past 10 years. The frequency of HLA homozygosity was found to be similar between haematological patients and control groups. It is important for an HLA laboratory to be aware of the differences in various HLA typing techniques' sensitivity for detecting an under-represented haplotype between HLA typing techniques when genotyping patients with haematological diseases. It is advisable for HLA laboratories to have at least two different methods with different sensitivities in their repertoire to be able to retype samples when a false homozygous result is suspected.

Late non-relapse mortality among adult autologous stem cell transplant recipients: a nation-wide analysis of 1,482 patients transplanted in 1990-2003.

Data on the incidence and causes of late (>100 d) non-relapse mortality (NRM) in autologous stem cell transplant (ASCT) recipients is limited. We have analysed NRM in a cohort of 1,482 adult patients who received ASCT in 1990-2003 in six Finnish transplant centres. The most common diagnoses included non-Hodgkin's lymphoma (NHL) (n = 542), multiple myeloma (MM) (n = 528), breast cancer (n = 132); Hodgkin's lymphoma (HL) (n = 86) and chronic lymphocytic leukaemia (CLL) (n = 63). Until September 2005, 646 patients (44%) have died. Late NRM was observed in 68 patients (4.6% of ASCT recipients; 11% of all deaths). There were 38 males and 30 females with a median age of 58 yr (20-69) at the time of ASCT. The median time to NRM was 27 months from ASCT (3-112). The risk of NRM was highest in patients with CLL (9.5%) and those with HL (8.1%) followed by MM and NHL (4.9% and 4.8%, respectively). The risk of late NRM was comparable in patients who received total body irradiation (TBI) and those who received chemotherapy-only regimens (6.7% vs. 4.3%). Another malignancy was the most common cause of late NRM (24 patients, 35% of late NRM). Twelve patients (0.8% of ASCT recipients) have died due to secondary haematological malignancy. Altogether 22 patients (32% of late NRM) died from infectious causes. Malignancies and late infections are important causes of NRM after ASCT. These facts point out the importance of prolonged follow-up in ASCT recipients.

Early treatment-related mortality in adult autologous stem cell transplant recipients: a nation-wide survey of 1482 transplanted patients.

OBJECTIVES: To evaluate early (<100 d) treatment-related mortality (TRM) in autologous stem cell transplant (ASCT) recipients. PATIENTS: Altogether 1482 adult patients received ASCT in six Finnish centres 1990-2003. The most common diagnoses were non-Hodgkin's lymphoma (NHL) (n = 542), multiple myeloma (MM) (n = 528), breast cancer (BC) (n = 132), Hodgkin's lymphoma (n = 86) and chronic lymphocytic leukaemia (CLL) (n = 63). RESULTS: Forty-two patients (2.8%) died from treatment-related reasons <100 d from ASCT. The median time to death was 38 d from ASCT (0-99). The risk of TRM varied according to the diagnoses. The highest risk was observed in patients with AL amyloidosis (24%) followed by NHL (4.4%) and MM (1.9%). No early TRM was observed in patients transplanted for BC or CLL. Infections were the cause of death in 16 patients (fungal 7, bacterial 6, viral 3). Organ toxicity was responsible for early death in 26 patients (heart 9, lungs 7, other 10). CONCLUSIONS: This nation-wide survey indicated a low early TRM in ASCT recipients in general, but higher risks in patients with AL amyloidosis or NHL. In addition to patient selection, also optimization of transplant procedure may be needed in these patient groups to reduce early TRM.

Outcome of progressive disease after autologous stem cell transplantation in patients with non-Hodgkin's lymphoma: a nation-wide survey.

OBJECTIVES: To analyse outcome and prognostic factors in non-Hodgkin's lymphoma (NHL) patients who progress after autologous stem cell transplantation (ASCT). PATIENTS: Altogether 115 consecutive NHL patients transplanted in 1991-2000 were studied. Histology included diffuse large B cell (n = 52), follicular (n = 26), mantle cell (n = 15), T cell (n = 16) and other subtypes (n = 6). The median time from ASCT to the progression was 7 months. Ninety-six patients (83%) received salvage treatment. RESULTS: Twenty-four patients (25%) achieved complete remission and 30 (31%) partial remission. The median overall survival was 8 months (range 0-98+) and the projected 4-year survival 21%. In multivariate analysis factors predicting treatment response after the progression included the use of rituximab (P = 0.036), histology other than diffuse large B cell (P = 0.001) and International Prognostic Index < or =2 at progression (P < 0.001). Normal lactate dehydrogenase (LDH) at progression (P = 0.002), response to salvage treatment (P < 0.001) and time from ASCT to progression > or =7 months (P = 0.022) were predictors for overall survival. CONCLUSIONS: Although the prognosis of patients who progress after ASCT is generally poor, many patients will respond to current therapies, and some may experience prolonged survival. Normal LDH at time of disease progression and longer time to progression after ASCT were the most powerful predictors for a promising outcome.

Invasive fungal infections in autologous stem cell transplant recipients: a nation-wide study of 1188 transplanted patients.

UNLABELLED: Based on small single-centre series, the risk of invasive fungal infections (IFI) has been considered small in autologous stem cell transplant (ASCT) recipients. PURPOSE: To analyse epidemiological and clinical features of (IFI) among ASCT recipients in Finland 1990-2001. PATIENTS: During the study period, 1188 adult patients received high-dose therapy supported by ASCT in six centres. Altogether, 1112 patients (94%) received blood progenitor cells. The graft was CD34+ selected in 261 patients (22%). The major diagnostic groups were non-Hodgkin's lymphoma (n = 417), multiple myeloma (n = 395), breast cancer (n = 132) and Hodgkin's lymphoma (n = 53). RESULTS: Eighteen patients (1.5%) with IFI were identified. The incidence of proven or probable invasive aspergillosis was 0.8%, followed by candidaemia with an incidence of 0.3%. The median time to the diagnosis of IFI was 35 d (6-162) from the progenitor cell infusion. In fourteen patients (78%) IFI was diagnosed during lifetime and they were treated with antifungal therapy for a median of 50 d. Nine patients (64%) were cured. CONCLUSIONS: IFI appears to be a rare event after ASCT and Aspergillus infections seem to be predominant. These epidemiological features have an impact in planning prophylactic and empirical antifungal strategies in ASCT recipients.

Autologous stem cell transplantation in adult patients with peripheral T-cell lymphoma: a nation-wide survey.

Limited experience is available on the feasibility and efficacy of high-dose therapy (HDT) supported by autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL). Therefore, a nation-wide survey was conducted in adult patients transplanted for PTCL in Finland during 1990-2001. After histopathology review, 37 patients were identified. The median age was 46 years (16-68) at the time of ASCT. Histology included PTCL not otherwise specified in 14 patients, anaplastic large cell lymphoma (ALCL) in 14 patients, and other in nine patients. Disease status at the time of ASCT was CR/PR1 in 18 patients; CR/PR2 in 14 patients, and other in five patients. HDT consisted of either BEAC (N=22) or BEAM (N=15), supported by blood stem cells in 34 patients (92%). Early transplant-related mortality was 11%. With a median follow-up of 24 months from HDT, 16 patients (43%) have relapsed or progressed. The estimated 5-year overall survival (OS) was 54%. Patients with ALCL had superior OS when compared with other subtypes (85 vs 35%, P=0.007). OS at 5 years was 63% in patients transplanted in CR/PR1 vs 45% in those transplanted in other disease status (P=NS). Prospective studies are needed to define the role of ASCT in this lymphoma type.

Amifostine does not protect malignant lymphoma cell lines from the cytotoxic effects of various chemotherapeutics in vitro.

The effect of amifostine on the cytotoxicity of melphalan, BCNU, doxorubicin and etoposide in lymphoma cell lines; HTB-61 (Burkitt), HTB-142 (nonspesified neck lymphoma), HTB-146 (Hodgkin's) and HTB 176 (Sezarýs syndrome) and a normal human fibroblast cell line was studied in vitro. Amifostine decreased etoposide induced cell kill in the fibroblast cell line. Pretreatment with the same amifostine concentration did not decrease the cytotoxic effects of etoposide, doxorubicin, melphalan and carmustine in lymphoma cell lines. Moreover, it even enhanced the cell killing effects of chemotherapeutics in especially HTB61 cell line. Our results indicate that amifostine does not decrease cytotoxicity of the chemotherapeutics and favor the testing of this drug in accordance with lymphoma treatments in clinical trials.

MMP-2 and MMP-9 expression in adult and childhood acute lymphatic leukemia (ALL).

In the present study the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in acute lymphatic leukemia (ALL) is studied with immunocytochemical staining in bone marrow aspirate smears from 75 patients. The material included 20 adult and 55 pediatric ALL patients. In 65% of the adult ALL cases the immunoreactive protein for either MMP-2 or MMP-9 or for both the enzymes was seen. A statistically significant correlation (P 0.027) with MMP-2 positivity and appearance of extramedullary infiltrates was found in adult ALL, suggesting that the gelatinase activity could be related with increased extravasation of the leukemic cells in ALL. This has to be confirmed in a larger patient population. In pediatric patients there were only seven cases (12.7%) out of 55 with positive immunostaining for either of these metalloproteinases. MMP expression correlated with L2 FAB class, high-risk tumor group and T-cell immunophenotype, but not with extramedullary presentation in pediatric patients with ALL indicating basic biological differences between adult and childhood ALL.

Gelatinase A and B (MMP-2, MMP-9) in leukaemia MMP-2 may indicate a good prognosis in AML.

We studied the expression of gelatinase-A (MMP-2) and gelatinase-B (MMP-9) in bone marrow aspirates from 54 patients with leukaemia. Specific staining patterns for different leukaemia subtypes are described. Most intresting were findings in acute myeloid leukaemia (AML), where MMP-2 staining correlated strongly with prognosis. Three year event-free survival after conventional treatment for patients with MMP-2 positive blast cells was 82%, while all the conventionally treated patients with MMP-2 negative blasts relapsed within 13.5 months. After treatment with allogeneic bone marrow transplantation, 3-year event-free survivals were 100% and 80% for MMP-2 positive and negative patients respectively.