Investigation of the RB-1 Tumour Suppressor Gene in a United Kingdom Series of Non-Hodgkin's Lymphomas

We have investigated the RB-1 tumour suppressor genes in a series of 20 non-Hodgkin's lymphomas (NHL). Polymerase chain reaction (PCR) amplification of polymorphic alleles indicated that there was evidence of allelic imbalance around 13q14, the site of the RB-1 gene, in at least 5 NHL. Immunohistochemical analysis of the RB-1 protein demonstrated wide variations in the percentage of cells exhibiting positive staining, but these usually correlated with differences in the proliferation index as indicated by staining of Ki67. Only 3/35 NHL exhibited significantly fewer cells expressing RB-1 protein than expressed Ki167. A comprehensive analysis of the mutation status of RB-1 in 20 NHL was carried out using PCR based strategies involving single strand conformational polymorphism (SSCP) gels. Most of the protein coding region was studied by analysing cDNA derived from its mRNA and the remaining 5'-end of the coding region investigated by analysing exon I of the gene. We also examined the promoter region of the gene. In none of the 20 NHL investigated were we able to identify a mutation; the only abnormal migrating fragment observed proved to be a polymorphism in exon I of the gene in 5 NHL. In one other case we detected instability at an intron repeat sequence, which had occurred during progression of the disease, but again no mutation of the protein coding region was found. The low levels of RB-1 protein expression that we had observed in a few of our NHL therefore did not appear to be due to mutation of the gene. These data suggest that mutation of RB-1 is not a common event in the evolution of NHL, but that there may be another, as yet unidentified, tumour suppressor gene near the RB-1 locus which is associated with NHL.     

Interferon-Inducible Protein-10 and the Pathogenesis of Cutaneous T-Cell Lymphomas

Human interferon-g inducible protein-10 (IP-10), a small basic protein secreted by interferon (INF)-g stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits early normal and leukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphoma (CTCL) is an indolent CD4-positive lymphoma characterized by multiple skin relapses before visceral dissemination. We investigated the role of IP-10 in the biology of CTCL by using immunocytochemistry to define IP-10 expression in normal and CTCL skin biopsies. Using purified recombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte proteins or any other chemokine. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal but not by differentiated keratinocytes. The epidermis overlying CTCL lesions was often hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patients for a frequency of 96%; and 95% confidence interval (CI) of 80% to 100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% Cl, 2% to 39%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was initially overexpressed before treatment but was normally expressed when he achieved remission. These results suggest that IP-10 may play a role in the epidermotropism of CTCL. More work is required to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be used to develop curative therapies for this disorder.     

Epidemiology of Primary CNS Lymphoma

In the beginning of the nineties the National Cancer Institute Surveillance, Epidemiology, and End Results Program calculated the incidence of primary central nervous system non-Hodgkin's lymphoma (PCNSL) as 1:100000. The incidence of PCNSL has been increasing since the seventies in immunocompetent patients. The main increase, however, is taking place since the mid-eighties and is due to the increase of immunodeficieny and immunosuppression. The risk is 2–6% in AIDS patients according to clinical data and will probably further increase with the length of survival in these patients. Transplant patients carry a risk of 1–5% to develop a PCNSL. The risk is 1–2% for renal, and 2–7% for cardiac, lung or liver transplant recipients. Patients with congenital immune deficiency have a risk of 4%. PCNSL may also present as a secondary malignancy.     

Clinicopathological Features, Survival And Prognostic Factors Of Primary Central Nervous System Lymphomas: Trends in Incidence of Primary Central Nervous System Lymphomas and Primary Malignant Brain Tumors in A Well-Defined Geographical Area; Population-Based Data from the Danish Lymphoma Registry, Lyfo, And the Danish Cancer Reistry

It has been claimed that Primary Central Nervous System Lymphoma! (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extrancdal non-Hcdgkin lymphomas (NHL), occur with increasing frequency in immunologically normal as well as in immunocompromised individuals. In an attempt to characterize the clinicopathological features, outcome and prognostic factors of PCNSL we here report our experience in a large unselected series of patients from a well-defined region. In addition, we present data on trends in incidence of PCNSL and primary malignant brain tumors in a well-defined geographical area. In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered during the approximate I I-year period from 1st January 1983 to 3 1st May 1994. Incidence data of primary malignant tumors of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate I I-year period 3 124 new cases of NHL were registered. Of these, I 152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for4.2% ofextranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was I .56 cases per million population (age range: 15-85 yrs, median: 62 yrs, MIF ratio: I).In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumors. Incidence of primary malignant brain tumors was stable, except for age ranges over 70 years. However, diagnostic artifacts might be responsible for this apparent increase. Histologically, 85% were high grade. Using the Kiel classification centroblastic diffuse (60%) and immunoblastic lymphoma (13%) were the most common subtypes. Forty-three patients had 6-cell lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed pre mortem. Treatment included surgical resection (26 patients), whole brain irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival for those receiving either WBRT or WkRT and chemotherapy was 8 months and 20 months, respectively (p = 0.78). Overall survival was 53%. 38% and 26% at I, 2 and 5 years. Cox-regression analysis identified only one factor having independent impact on survival in PCNSL performance score 2 2 (pc 0.001. RR = 5.8     

Neurologic Sequelae of Treatment of Primary CNS Lymphomas

Novel efficient and aggressive treatment protocols for primary CNS lymphomas have resulted in an increasing number of long term survivors. Follow up data show that in a substantial fraction of these patients, treatment benefits are overshadowed by neurotoxic sequelae. Neurotoxicity especially affects the older age group, presenting as cognitive dysfunction, ataxia or dementia as a consequence of leukoencephalopathy and brain atrophy. The combination of radiotherapy and chemotherapy seems to be particularly hazardous, though data are too sparse to draw any definite conclusions yet. Long term follow up of patients included in clinical studies therefore should not only evaluate survival or time to tumour progression, but also serial neuropsychometric evaluation and quality of life assessment.     

The Integrated Histopathologic and Molecular Approach to Adult-type Diffuse Astrocytomas: Status of the Art,Based on the 2021 WHO Classification of Central Nervous System Tumors

The 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS)improved our understanding of the brain neoplasm biology. In more details, differences between diffuse gliomasthat primarily occur in adults and those that primarily occur in children have been identified by the terms “adult-type” and “pediatric-type” diffuse gliomas. More importantly, both diagnostic and grading criteria for adult-typediffuse astrocytomas have been modified, by adopting novel molecular markers: diffuse astrocytomas, IDH-mutant have been grouped into a single entity and graded as CNS WHO grades 2, 3, or 4, with the assignmentof Grade 4 in the presence of CDKN2A/B homozygous deletion, regardless of the histology [1]. Additionally, atleast one of the following genetic alterations has been considered as sufficient to confer to astrocytomas, IDH wildtype, a CNS WHO grade 4: i) TERT promoter mutation, ii) EGFR gene amplification, iii) combined gain of wholechromosome 7 and loss of whole chromosome 10 [+7/−10]. However, histology remains the solid basis to supportthese new complementary molecular data, and an integrated diagnosis is highly recommended.     

Pathology and Pathogenesis of T-Cell Lymphoma

Peripheral T cell lymphomas (PTCLs) are a heterogeneous and often clinically aggressive group of neoplasms derived from mature post-thymic T lymphocytes. These neoplasms are rare and usually diagnostically challenging. Our understanding of the pathogenesis of PTCL is increasing and this improved knowledge is leading us to better molecular characterization, more objective diagnostic criteria, more effective risk assessment, and potentially to better treatments for these neoplasms.     

The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: a sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide.

BACKGROUND: The NHL-15 protocol is a novel, dose-intense, dose-dense, sequential chemotherapy program developed to improve outcome in advanced, aggressive non-Hodgkin's lymphomas. PATIENTS AND METHODS: The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m(2) i.v. on weeks 1, 3, 5 and 7 plus vincristine 1.4 mg/m(2) i.v. (no cap) on weeks 1, 2, 3, 5 and 7]; and (ii) consolidation (cyclophosphamide 3000 mg/m(2) i.v. on weeks 9, 11 and 13 plus granulocyte colony-stimulating factor 5 microg/kg subcutaneous on days 3-10 following each cyclophosphamide dose). Patients with aggressive non-Hodgkin's lymphomas (working formulation: intermediate grade or immunoblastic), bulky stage I and stages II-IV, were eligible. RESULTS: There are 165 eligible patients with a 6.9-year median follow-up (range 0.5-141 months) and a median age of 48 years. For the entire group, 72.1% achieved complete remission, and at 5 years disease-free survival was 57.8% and overall survival (OS) was 62.2%. Ideal dose delivery was >90%. Acute and late toxicities of treatment were manageable and acceptable. Toxic death on treatment was 2.4%. When the diffuse large cell lymphoma histologies were grouped according to the International Prognostic Index (IPI), complete remission and OS in the low-intermediate (LI), and high-intermediate (HI) risk groups were improved by 5%-15% compared with historical CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). This improvement was also noted for LI and HI risk groups in the age-adjusted (aa)IPI analysis for patients < or =60 years of age. CONCLUSIONS: The NHL-15 program can be administered safely and effectively to achieve high rates of durable remission when used for the treatment of advanced stage, aggressive, non-Hodgkin's lymphomas. The 5%-15% improvement in 5-year OS compared with historical CHOP, according to the IPI/aaIPI model (in LI and HI risk groups), is encouraging. Further evaluation and prospective testing of the NHL-15 protocol appears to be warranted.     

Detection and Relevance of Minimal Disease in Lymphomas

The detection and clinical relevance of minimal disease in non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) is reviewed. Relevant aspects of the basic biology of these diseases are introduced, including the interactions of NHL with bone marrow stromal cells and the consequences of suppressed apoptosis and induced chemoresistance which might explain why minimal lymphoma in bone marrow is a surrogate predictor of a poor clinical outcome. In contrast, NHL cells isolated from stroma, for example mobilized into blood by cytokine, may be more susceptible to apoptosis and clinically less significant. The possible role of angiogenesis in facilitating early metastasis to the bone marrow is considered. Methods of detecting minimal NHL are reviewed and differences in predictive reliability of tumor detected by culture methods versus molecular techniques which identify clonal bcl-2 or antigen receptor rearrangements are discussed. The role of detection of HD by analysis of unique rearrangements of the immunoglobulin heavy and light chain genes is discussed as is the possibility that Reed–Sternberg (RS) cells can be detected molecularly as well as grown in culture from blood and apheresis harvests of patients. It appears that patients with cells resembling RS cells in their harvest do less well following high dose therapy and transplantation and additional studies of this topic are warranted. Future developments including quantitative monitoring of disease burden by real-time automated PCR and the application of genetic profiling to identify genetic markers specific to the tumor and which, potentially can predict prognosis is suggested. Also, the problems which may arise in attempts to monitor the impact of newer therapies such as anti-lymphoma antibodies and vaccines which may preferentially deplete tumor cells from blood and marrow are considered. The past 10 years has witnessed dramatic progress in the application of techniques to monitor minimal lymphoma. This technology has helped demonstrate the success of some new therapeutic approaches e.g. antibody and vaccine therapies, and served to emphasize the failure of others, for example, stem cell selection to purge lymphoma from patient harvests. Technologically, the field is not yet mature and further evolution may be expected.     

胃癌分子分型研究进展

胃癌是全球性常见的恶性肿瘤.胃癌是一种异质性疾病包括多种类型,每种类型都有不同的生物学特性和作用.因此,基于临床特点,病理分型,分子分型的个体化治疗对进展期胃癌尤为重要.现有的胃癌分子分型可归类为Shah分型,Tan基因分型,新加坡基因分型,TCGA基因分型和ACRG基因分型.从分子生物学创立引起肿瘤治疗模式的变化,从分子水平重新认识疾病,未来的肿瘤治疗模式可能是分子分型指导的个体化治疗.     

MACOP-B vs F-MACHOP Regimen in the Treatment of High-Grade Non-Hodgkin's Lymphomas

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities.

Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACOP-B than among those given F-MACHOP (11% vs 3.5%). Higher incidences of severe cytopenia (51% vs 21%) and of fatal sepsis (5% vs 2%) were recorded among patients treated with F-MACHOP than with MACOP-B.

The third-generation regimens, F-MACHOP and MACOP-B, are as effective as other regimens. A prognostic analysis taking into account the principal covariates (age, symptoms, stage, serum lactate dehydrogenase, mediastinum involvement, bulky disease, histology, therapy, and dose intensity) was assessed for their impact on complete response rate incidence and on relapse rate from complete response by multivariate analysis. The linear logistic model showed that symptoms, advanced stage, mediastinum involvement, and bulky disease are prognostic factors that increase the risk of a lower rate of complete response. These data confirm the important role of a pretreatment selection for the poor-risk patients and, on the basis of these parameters, it will probably be possible to consider these patients for high-dose therapy with autologous bone marrow transplantation or autologous hematopoietic stem-cell support.     

Peripheral T-Cell Lymphomas Respond Well to Vincristine, Adriamycin, Cyclophosphamide, Prednisone and Etoposide (VACPE) and Have a Similar Outcome as High-Grade B-Cell Lymphomas

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of T-cell malignancies including subentities with favourable (large cell anaplastic) or unfavourable (pleomorphic) prognosis. The clinical outcome of PTCL has been controversially discussed, but a worse prognosis than high-grade B-cell Non-Hodgkin's lymphomas (NHL) has been postulated by most authors. In this report we summarize the results of a prospective comparative study investigating the therapy outcome of 27 patients (pts) with PTCL and 55 pts. with high grade B-cell NHL and give an overview of therapy studies in PTCL. The histological sub-types were 14 pleomorphic, 8 large-cell anaplastic (Ki-1+), 2 angioimmunoblastic (AILD) and 3 other PTCL. In three patients the PTCL was associated with non-tropical sprue (11%). Nineteen patients presented with an advanced stage of disease (stage III and IV, 70%), 17 (63%) pts. had B-symptoms. The patients were treated with vincristine 2 mg dl, adriamycin 25 mg/m² dl-3, cyclophosphamide 800 mg/m² dl, prednisone 60 mglm² dl-7 and etoposide 120 mg/m² dl-3 (VACPE). In 77% of pts. with PTCL and 84% of patients with high-grade B-cell NHL a complete remission (CR) was achieved. 75% of the complete responders with PTCL and 70% with B-NHL are still in ongoing CR. The subgroup of large-cell anaplastic attained a CR in 88%. The median observation time is 44 months (1+-77+). The probability of 1-, 3- and 5-year overall and disease-free survival for the T-cell group were 76%, 54%, 48% and 76%, 62%, 62%, respectively according to Kaplan-Meier. There was no significant difference regarding the remission rate, the overall-, event-free or disease-free survival compared to high-grade B-cell lymphomas.

In conclusion, the VACPE regimen is an effective and feasible regimen in the management of PTCL achieving complete remissions in a large proportion of patients.     

22例胃粘膜相关淋巴瘤临床病理及免疫表型分析

目的：探讨胃粘膜相关淋巴瘤的临床病理特点。方法：收集22例胃原发性恶性淋巴瘤.应用MALT概念进行形态学及免疫组化分析。结果；本级资料显示临床以中年人多见．男女性别之比为1.4：1。病变好发于胃窦、体部。22例经免疫组化证实均为B细胞性淋巴瘤。其中6例病理形态学呈典型MALT淋巴瘤，13例呈不典型MALT淋巴瘤。3例肿瘤由单一高度恶性中心母细胞样细胞组成，其中2例内可见LEL现象和浆细胞浸润。结论：胃原发性B细胞性淋巴瘤均为MALT淋巴瘤。单一星高度恶性图像的淋巴瘤可能是MALT淋巴瘤转化的一个阶段。     

Prediction of Pathology and Survival by FDG PET in Gliomas

Objectives: Despite being in use for nearly two decades, the utility of [18F]2-fluoro-2deoxy-d-glucose positron emission tomography (FDG PET) in the evaluation and treatment of brain tumors remains controversial. We retrospectively analyzed all patients with histologically proven gliomas, between the years 1990 and 2000, who underwent FDG PET studies at various stages of their treatment and who were followed till either death or for a minimum period of 1 year in an attempt to bring resolution to this controversy. Methods: All PET scans prior to 1997 were acquired on an ECAT 951/31 scanner in 2D. Scans since 1997 were obtained on a Siemens HR+ scanner in 3D mode. The majority of FDG PET scans were co-registered with the magnetic resonance imaging (MRI) scans to aid in diagnosis and therapy. Based on independent visual inspection, two board certified nuclear medicine physicians graded the highest activity level of the tumor using the metabolic grading: 0 = no uptake; 1 = uptake less or equal to normal white matter; 2 = uptake greater than normal white matter and less than gray matter; 3 = uptake equal to or greater than gray mater. The measure of association of lambda was used to measure the strength of predictive ability of FDG PET for pathological grading of the gliomas. The Cox proportional hazards regression model was used to assess the significance of grade of uptake on survival. Results: A total of 331 patients were analyzed of which 137 had a PET scan prior to histological diagnosis and therapeutic intervention (mean age = 46.5years; M:F = 1.7:1). Eighty six percent (143/166) of the patients with low uptake (metabolic scores 0,1) had low-grade gliomas (grade I,II) and 14% (23/166) high-grade gliomas (grade III,IV) on histologic examination. Ninety four percent (154/165) of the patients with high uptake (metabolic scores 2,3) on PET had high-grade gliomas and 7% (11/165) had low-grade gliomas on histologic examination. The grade of uptake had increasing significance on survival as the level increased from 'low' to 'high' (P = 0.0009). Ninety four percent (156/166) of the patients with low uptake survived for >1 year (median survival of 28 months) and 19% survived for >5 years. Only 29% (48/165) of patients with high uptake survived for >1 year, (median survival of 11 months) and none survived for >5 years. Irrespective of when the scan showed a high uptake of FDG, before or after intervention, the prognosis following that scan was poor. Conclusions: Our observations confirm the utility of FDG PET as a prognostic tool for the histological grading and survival in patients with gliomas and appears to more than complement pathological grading.     

Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profiles

Ovarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor. An accurate classification was not achieved using an unselected set of 1,584 protein spots for clustering analysis. Different approaches were used to select spots that were differentially expressed between tumors of different malignant potential and to use these sets of spots for classification. When sets of proteins were selected that differentiated benign and malignant tumors, borderline tumors clustered in the benign group. This is consistent with the biologic properties of these tumors. Our results indicate that hierarchical clustering analysis is a useful approach for analysis of protein profiles and show that this approach can be used for differential diagnosis of ovarian carcinomas and borderline tumors.     

Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries

Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004–2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004–2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984–2000) and (4) the US National Cancer Data Base (1990–2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries.     

Effect of Granulocyte-Macrophage Colony-Stimulating Factor on Chemotherapy-Related Neutropenia in Patients with Non-Hodgkin's Lymphomas—A Phase I/II Study of Dose and Mode of Administration

The effect of mammalian glycosylated recombinant granulocyte-macrophage colony-stimulating factor was investigated in 24 patients with newly diagnosed non-Hodgkin's lymphoma in a phase I/II study. All patients received standard chemotherapy with CHOP. RhGM-CSF was administered after the first cycle for 5 days, and at one of four dose levels (2, 4, 8 and 16 μg/kg). Patients were randomized to receive the drug either by continuous intravenous infusion or twice daily as subcutaneous injection.

No significant difference in results was observed between subcutaneous administration of rhGM-CSF and continuous i.v. infusion and these patient groups could therefore be combined in the analysis.

Administration of rhGM-CSF resulted in a significant dose-dependent increase of total WBC, mainly neutrophils, eosinophils and monocytes. The increase was observed in 18/24 patients, reaching a peak 24-72 (median 24) hours after the start of rhGM-CSF. The CHOP chemotherapy-induced leucocyte nadir occurred on day 12 (mean) compared to day 14 for the 127 historical controls. The WBC nadir values were higher (2.4 ± 1.4) than for historical controls (1.8 ± 1.1) and the leucopenic/neutropenic period was of shorter duration. Following the chemotherapy nadir a more rapid recovery of WBC was seen than in controls. GM-CSF was well tolerated, the side effects were mild and transient, and included myalgias, low grade fever, headache, chest/bone discomfort, nausea, erythema at injection site and superficial phlebitis.

The encouraging results of this phase I/II study indicate the need for a prospective controlled study of GM-CSF in chemotherapy of malignant lymphoma.