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J C Kluin-Nelemans

Publications and source records attributed to J C Kluin-Nelemans.

At least 73 records · Page 4Linked to original sources

International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades.

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

Aged↗

Presenting signs and symptoms in multiple myeloma: high percentages of stage III among patients without apparent myeloma-associated symptoms.

We studied the medical histories of 127 patients diagnosed with multiple myeloma included in a population-based registry of 945 patients with a para-protein or multiple myeloma in the region of the Comprehensive Cancer Center West (CCCW). We defined patients "not immediately diagnosed" or "delayed diagnosis" as those patients in whom myeloma was not included in the initial differential diagnosis. We found that 37% belonged to this category. These patients more often had symptoms not associated with multiple myeloma. Since a surprising 51% of patients with delayed diagnosis turned out to have stage-III myeloma, the physician should be alert to the presence of this disease, despite the fact that co-morbidity may mask its presence.

Adult↗

Is the Durie and Salmon diagnostic classification system for plasma cell dyscrasias still the best choice? Application of three classification systems to a large population-based registry of paraproteinemia and multiple myeloma.

There are a number of systems for diagnosing multiple myeloma, myeloma variants and monoclonal gammopathy of undetermined significance. We compared three systems, those according to Durie and Salmon, to Kyle and Greipp, and to the British Columbia Cancer Agency, using material from a population-based registry of 847 patients with a paraproteinemia or multiple myeloma. Of these, 157 underwent both bone marrow and X-ray examinations and were subsequently included in our analysis. The differences between the systems were small, even though in only 64% of the cases the diagnosis according to all three systems was identical. The system used by the British Columbia Cancer Agency turned out to be the shortest and easiest system reviewed here. We propose a more frequent application of this system instead of the more commonly used Durie and Salmon and Kyle and Greipp criteria.

Adult↗

High-dose Ara-C for remission induction and consolidation of previously untreated adults with ALL or lymphoblastic lymphoma.

Thirty-two patients with untreated ALL (n = 26) or lymphoblastic lymphoma (n = 6) between 17 and 65 years of age were treated with a short remission induction course with VP16-213, amsacrine, intermediate dose Ara-C for 6 days, prednisone and intrathecal methotrexate, followed by a consolidation course with vincristine, amsacrine, high dose Ara-C for 4 days, prednisone and intrathecal methotrexate. After subsequent cranial irradiation, no further maintenance was planned. However, some patients underwent an allogenic (n = 5) or autologous (n = 5) bone marrow transplantation after the consolidation treatment. Twenty-three of 32 patients (72%) achieved a complete remission. Ten of 13 patients with T-ALL or lymphoma, six of eight patients with pre-B or common ALL, and seven of 11 patients with B-ALL or Burkitt's lymphoma achieved a complete remission. The median duration of remission was 24 months. Overall survival for the whole group was 35% at 5 years. The disease-free survival was 45% at 5 years. Long-term survival for patients with B or T-ALL was approximately 60%, compared with 15% for those with common or pre B-ALL. Short term intensive courses including intermediate or high dose Ara-C during remission and consolidation treatment lead to results comparable to those obtained with long-term maintenance regimens. Our regimen may be sufficient for patients with T or B-ALL. Larger randomized studies are needed to investigate the relative importance of our observations.

Adolescent↗

Fatal infectious mononucleosis: a severe complication in the treatment of Crohn's disease with azathioprine.

A 19 year old man with a history of Crohn's disease treated with azathioprine and prednisone, died after a primary infection with Epstein-Barr virus. He had the characteristics of the virus associated haemophagocytic syndrome, a rare complication of viral infections, which consists of fever, constitutional symptoms, hepatosplenomegaly, liver function and coagulation abnormalities, and hypertriglyceridaemia. Additionally, there was pain, cytopenia, and histiocytic hyperplasia in the bone marrow, spleen, or lymph nodes. This severe complication has been reported previously in renal transplant patients, but not in those with inflammatory bowel disease taking azathioprine. The immunosuppressive therapy may have contributed to this fatal complication of infectious mononucleosis, and this complication should be considered when treating a patient with inflammatory bowel disease with azathioprine.

Adult↗

Efficacy of four different regimens in 64 mantle-cell lymphoma cases: clinicopathologic comparison with 498 other non-Hodgkin's lymphoma subtypes. European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: Before recognizing mantle-cell lymphoma (MCL) as a distinct entity, these patients were grouped into low-grade (LG) or intermediate-/high-grade categories (IGHG) according to the Working Formulation and received various therapies. This was a unique opportunity to evaluate characteristics, behavior, response to treatment, and outcome of patients with MCL from two phase III trials conducted by the European Organization for the Research and Treatment of Cancer (EORTC): EORTC 20855 IGHG and EORTC 20856 LG. PATIENTS AND METHODS: After histologic review, 64 diagnosed MCL patients (29 IGHG and 35 LG) were compared with other patients in their respective trials. In the IGHG group, patients received cyclophosphamide, doxorubicin, teniposide (VM26), prednisone, vincristine, and bleomycin (CHVmP-VB) or modified doxorubicin, cyclophosphamide, etoposide (VP 16), mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE-MOPP). In the LG group, after receiving cyclophosphamide, vincristine, and prednisone (CVP) induction, patients were randomized between maintenance treatment with interferon alfa-2a (IFN) or no further treatment. RESULTS: MCL patients compared with IGHG subtypes showed a similar overall survival and response rate, but shorter duration of response and progression-free survival. Comparing with LG patients, their response rate, duration of response, and progression-free survival showed no difference, while their overall survival was nearly twice shorter. MCL patients treated with CHVmP-VB had the longest survival. No treatment showed any significant improvement in terms of progression-free survival. CONCLUSION: These data confirm that MCL represents a clinicopathologic entity. In terms of survival, it behaves like IGHG subtypes, while in terms of progression-free survival, it behaves like LG lymphoma. It is still not clear which first-line treatment offers patients with MCL the best chance to obtain both a complete response (CR) and a long-term survival.

Adolescent↗

Histological conversion of follicular lymphoma with structural alterations of t(14;18) and immunoglobin genes.

About half of the patients with follicular lymphoma will develop an aggressive B cell lymphoma with morphological changes in growth pattern and cellular morphology. Changes of the immunophenotype, especially of the expression of immunoglobulin (Ig) have been documented less frequently. Multiple tumor samples of two patients with follicular lymphoma who developed tumor progression, were studied by Southern blot analysis for rearrangements of the Ig genes and the oncogenes BCL2 and MYC. In both patients, the general pattern of Ig gene rearrangements, especially of the Ig light-chain genes, and the structure of the t(14;18) breakpoint as assessed by the polymerase chain reaction (PRC) and fine restriction mapping, remained unaltered with time. However, both within the functional Ig heavy-chain allele and around the t(14;18) breakpoint, extensive secondary alterations took place. This indicates clonal evolution rather than the appearance of an independent lymphoma. In the first case with progression from follicular lymphoma to Burkitt's lymphoma 3 years after diagnosis, alterations were especially present 3' of the t(14;18) breakpoint. In the second patient with a change from follicular to diffuse centroblastic lymphoma 4 years after diagnosis, subsequent class switches from IgM to IgG and to defective IgH expression were accompanied by deletion of C mu sequences and a rearrangement of the MYC gene, respectively. Additionally, in both patients alterations in individual restriction sites occurred, which most likely were due to somatic mutations within both the functional IgH and translocated allele. Our data indicate that complex alterations of both the functional and non-functional IgH allele may accompany tumor progression and may erroneously suggest the appearance of independent clones by Southern blot analysis. It remains to be established whether these alterations are causative events or the consequence of genetic instability and clonal evolution.

Adult↗

Bcl-2 protein expression is not related to short survival in multiple myeloma.

The oncoprotein bcl-2 can be expressed in malignant plasma cells and might play a role in the prevention of corticosteroid-mediated apoptosis, thereby prolonging survival of the myeloma cells. We retrospectively investigated whether bcl-2 expression in bone marrow plasma cells measured by two-color fluorescence for immunoglobulin light chains would be related to survival duration in patients suffering from multiple myeloma. In all patients the large majority of plasma cells expressed bcl-2 (median 91%, range 74-100%). Contrary to our expectations, a tendency was observed toward higher percentages bcl-2+ plasma cells in patients with a long survival (more than 5 years, n = 9) vs patients who died from refractory myeloma within a year of diagnosis (n = 7). This tendency was found even when analysis was extended to include four patients in the short diagnosis group (n = 11) who had received chemotherapy prior to bone marrow examination.

Adult↗

Abnormally activated T lymphocytes in the spleen of patients with hairy-cell leukemia.

Hairy-cell leukemia (HCL) is a B-cell leukemia, but many factors argue for a T-cell dysfunction and/or involvement in this disease. Hairy cells typically home in the spleen, and become circulating only late in the disease. As it is assumed that the T-cell abnormalities are caused by specific interactions with the hairy cells, we studied the immunophenotype in 17 cases (CD3, CD4, CD8, CD45R0, TCR gamma delta) and cytokine gene expression in four cases (IL-1 beta, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, IFN-gamma, TNF-alpha, GM-CSF and the receptors of IL-1 and IL-2, using the cDNA-PCR technique) of purified T-cell fractions from hairy-cell spleens. By Northern blot analysis, mRNA for IFN-gamma, GM-CSF, IL-10 and TNF-alpha was measured in purified T cells and hairy cells from three HCL spleens. The results of the immunophenotype and cDNA-PCR data were compared with ten normal spleens. Compared to blood, splenic T cells showed a reversed CD4/CD8 ratio, a normal percentage of memory T cells, and an increase in CD3+TCR gamma delta + cells. Without specific induction spontaneous cytokine gene expression of IL-2, IL-4, IFN-gamma, and GM-CSF was seen in the purified T-cell fractions without signals in the purified hairy-cell fractions. mRNA expression of IFN-gamma and GM-CSF in the T cells, and of IL-10 and TNF-alpha in the hairy cells was confirmed by the Northern blot technique. From these data we suggest that splenic T cells in HCL should not be considered as residual or recirculating T cells, but rather as tumor-infiltrating lymphocytes.

Blotting, Northern↗

Lactic acidosis in a patient with B-cell non-Hodgkin's lymphoma.

A patient with an intermediate grade B-cell non-Hodgkin's lymphoma who presented with severe dyspnea caused by lymphoma-related lactic acidosis is described. The serum lactate and pyruvate levels paralleled the disease activity. Although oncologists are familiar with the relationship between bulky solid tumors and lactic acidosis, well-documented lymphoma cases are extremely rare.

Acidosis, Lactic↗

[Sweet's syndrome (acute febrile neutrophilic dermatosis)].

The clinical presentation and the relation with malignancy of acute febrile neutrophilic dermatosis in 7 patients are described. The syndrome is characterised by fever, neutrophilic granulocytosis, painful erythematous plaques and typical histology consisting of a dense dermal infiltrate of mature neutrophils. The idiopathic form (80% of reported patients) usually follows a viral infection. The secondary form (20% of reported patients) is associated with a malignancy, which in the large majority (85%) is a hematologic disorder (this was the case in 3 of the 7 patients); the course of the syndrome may then be serious. The secondary form of the disease may be associated with an exacerbation of a preexistent malignancy, as was seen in 2 of the 3 patients. If the syndrome runs a serious course the treatment consists of corticosteroid administration.

Adult↗

Acute lymphoblastic leukaemia in adults: immunological subtypes and clinical features at presentation.

In 91 of 106 adult patients with acute lymphoblastic leukemia (ALL) enrolled in the treatment protocol ALL HOVON-5 between May 1988 and October 1991, the immunophenotype of the leukemia was determined and correlated with clinical characteristics at presentation. The immunological marker analysis was performed in ten laboratories, all members of the Dutch Study Group on Immunophenotyping of Leukemias and Lymphomas (SI-HON). Undifferentiated blasts were found in four patients, 67 had B-lineage ALL, 18 had T-lineage ALL, and two had biphenotypic ALL. The age of T-lineage ALL patients was lower (mean 29.3) than that of B-lineage ALL patients (mean 35.5). Tumor mass, as expressed by leukocyte count, organomegaly, and LDH, was more pronounced in T-lineage ALL. Hemoglobin and platelet count was similar in all (sub)types. CD34 was expressed in 58% of the leukemias, but most frequently in the common B-ALL (70%). Thirteen percent of the leukemias expressed one or more markers not associated with their lineage. In this prospective study immunological data were not evaluable for 15 patients. On four of them data were not available because of dry tap, for six patients the typing was technically insufficient, and for four patients the results were unclassifiable; with one patient the marker analysis was not performed.

Adolescent↗

Separation, enrichment, and characterization of human hematopoietic progenitor cells from umbilical cord blood.

Human umbilical cord blood (UCB) may be used as an alternative source of bone marrow repopulating cells in allogeneic bone marrow transplantation in children. It has been reported that high numbers of hematopoietic progenitor cells (HPC) from umbilical cord blood may be lost during simple cell-separation techniques. This may seriously hamper the use of UCB as an alternative source of bone marrow repopulating cells. In this study we demonstrate that UCB can be separated into various cell fractions using several cell-separation methods including red blood cell lysis, methylcellulose sedimentation, and density gradients without significant loss of HPC, when cell separations are initiated within 8 h. We demonstrate that UCB contains a high concentration of immature HPC as compared with bone marrow grafts. Using FACS analysis of cells harvested from single colonies derived from single cell- single well-sorted CD34++ CD33- UCB cells, the high frequency of multipotential HPC was illustrated. These results suggest that UCB may contain sufficient HPC for hematopoietic stem cell transplantation in adults.

Antigens, CD↗