Extreme leucocytosis and splenomegaly in metastasised melanoma.

A 63-year-old woman presented to the internist with fatigue, cough, low-grade fever, splenomegaly and leucocytosis up to 130 x 10(9)/l. Although a diagnosis of chronic myelogenous leukaemia was initially entertained, she turned out to have a metastasised melanoma. The differential diagnosis and workup is discussed, as well as potential mechanisms by which the tumour could have induced the leucocytosis, such as the production of G-CSF or similar mediators, and the prognostic significance of this phenomenon.

Comparison of allogeneic T cell-depleted peripheral blood stem cell and bone marrow transplantation: effect of stem cell source on short- and long-term outcome.

We report the results of a retrospective single-center study comparing engraftment, acute and chronic GVHD, relapse and survival in patients with malignant hematological disorders transplanted with allogeneic peripheral blood stem cells (alloPBSCT, n = 40) or bone marrow cells (alloBMT, n = 42). All transplants were T cell depleted by in vitro incubation with the Campath-1 monoclonal antibody. Primary graft failure occurred in none of the patients receiving an alloPBSCT compared with 3/42 of the recipients of an alloBMT. In addition, two patients in the alloBMT group showed no platelet engraftment. Recipients of PBSC had a more rapid recovery of neutrophils (median 14 days) compared to BM transplant recipients (median 32 days). Platelet recovery was also accelerated in PBSC recipients compared to BM recipients (11 vs 38 days). There was an increase in the incidence of grade II acute GVHD and chronic GVHD in patients after alloPBSCT (18% and 23%, respectively) compared to patients receiving alloBMT (5% and 8%, respectively). The 2-year cumulative incidence of relapse was similar in both groups (47%). At 6 months after transplantation, transplant-related mortality (TRM) was lower in PBSCT recipients than in BMT recipients. However, at a follow-up of 3 years TRM was similar in both groups. The disease-free survival rate at 3 years after transplantation did not differ between the groups (42% for PBSCT and 41% for BMT recipients). Our results indicate that T cell-depleted alloPBSCT compared to alloBMT is associated with a more rapid hematopoietic reconstitution and a decreased TRM at 6 months follow-up after transplantation. However, at a follow-up of 3 years, no sustained survival benefits were observed.

Specific cutaneous infiltrate caused by Staphylococcus aureus in a patient with chronic myelomonocytic leukemia.

We present a patient with chronic myelomonocytic leukemia who showed disseminated papules and nodules. Arguments in favor of leukemia cutis are the clinical appearance, the cyclic pattern with which the lesions appeared and disappeared, and the histologic features. The lesions reproducibly responded to treatment with antibiotics given for a Staphylococcus aureus infection. We speculate that at least in some patients, leukemic cells are recruited in the skin because of local infection and do not merely reflect autonomous growth but an inflammatory response.

Reactive hemophagocytic syndrome as a presenting feature of Hodgkin's disease.

We report the case of a 60-year-old man with fever of unknown origin, severe pancytopenia, and rapidly developing splenomegaly due to reactive hemophagocytic syndrome and Hodgkin's disease. Reactive hemophagocytic syndrome is often rapidly fatal and, once this diagnosis is considered, an underlying infection or malignancy should be treated promptly. An extensive search of the literature revealed only two other cases of reactive hemophagocytic syndrome and Hodgkin's disease. This is the only reported patient who survived after being diagnosed as having reactive hemophagocytic syndrome and Hodgkin's disease.

Severe hepatitis and pure red cell aplasia in adult Still's disease: good response to immunosuppressive therapy.

Adult-onset Still's disease is a systemic inflammatory disorder with a highly variable clinical course. Mild hepatitis and anemia are common manifestations. We describe a patient with adult Still's disease who developed a severe hepatitis and a life-threatening pure red cell aplasia. The hepatitis developed after treatment with NSAIDs was started. The patient was successfully treated with a combination of prednisone, cyclosporin, and methotrexate. Physicians should be aware that severe hepatitis and pure red cell aplasia can occur in adult Still's disease. We recommend a careful monitoring of liver functions in patients with adult Still's disease who are being treated with NSAIDs.

A second case of hexasomy 8 in myelodysplastic syndrome.

Tetrasomy 8 is a rare form of acquired aneuploidy found exclusively in the myeloid leukemias. Hexasomy 8 is even rarer: only one case has been reported, thus far. We describe here the second case of hexasomy 8 as the sole abnormality in an elderly female patient with myelodysplastic syndrome (MDS).

[The Diagnostic Compass; a new contribution to diagnostics]. / Het Diagnostisch Kompas; een nieuwe bijdrage aan de diagnostiek.

The Hospital Council has now issued a Diagnostic Compass besides the Pharmacotherapeutic Compass. Its objective is to contribute to a more rational and effective use of diagnostic examinations. The target group comprises physicians involved in using diagnostic tests. The information supplied is based on results of scientific research and don current habits, standards and guidelines. The book has two different approaches: clinical pictures and diagnostic tests. The two volumes are intended to supplement one another.

A case of isodicentric 7p as sole abnormality in a patient with acute myeloid leukemia.

The detection of isochromosomes in the leukemias and in solid tumors has been well described in the literature, the most common being the i(17q), which is found in the blast crisis of CML and terminal stages of acute myeloid leukemia. Reports of isochromosome 7 have, however, been less well represented, particularly isochromosomes of the short arm of chromosome 7, which represent approximately 1% of all reported isochromosomes in neoplasia. We present here a case report of an elderly female patient with AML-M2 who manifested an idic(7p) in the majority of her bone marrow cells. Fluorescence in situ hybridization (FISH) studies with both centromere-7--and chromosome-7--specific DNA probes verified the diagnosis of idic(7p). To the best of our knowledge, this is the first report of this type of leukemia with an acquired idic(7p) as the sole cytogenetic abnormality.

The H1 automated differential counter in determination of bone marrow remission in acute leukemia.

One hundred eighty-one bone marrow aspirates from 63 patients with acute leukemia were evaluated by the Technicon H1 automated differential counter and by microscopic examination for remission status after chemotherapy. Of the 163 marrows that were conclusive by microscopic examination, 130 were in remission (< 5% blast cells). This study focused on the following H1 alarms/flags to estimate their sensitivity for determination of remission: blast signal (BLSI), large unstained cells alarm (LUCA), baso blast alarm (BBLA), immature granulocytes (IGA) and atypia (ATYP). Basoblast alarm and BLSI revealed to be the most sensitive alarms (P < .0000 both), with 6 and 7 false-negative cases, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and efficiency were: 79%, 92%, 70%, 94%, and 89%, respectively for BLSI, and 82%, 90%, 68%, 95%, and 88%, respectively for BBLA. Blast signal and BBLA did not turn up in 67 hematologically normal bone marrows. In conclusion, the H1, the baso channel in particular, is a sensitive and specific tool for estimation of bone marrow remission status in acute leukemia.

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.

Recommended procedures for the classification of acute leukaemias.

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukaemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukaemia.

Recommended procedures for the classification of acute leukaemias. International Council for Standardization in Haematology (ICSH).

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukemia.

Decrease of memory T helper cells (CD4+ CD45R0+) in hairy cell leukemia.

Patients with hairy cell leukemia (HCL) are prone to opportunistic infections, which suggests an impaired T-cell functioning. To investigate a possible mechanism of such an impairment, we determined the numbers of naive and memory T cells by measuring the expression of CD45R0 on CD4+ and CD8+ T cells in 23 HCL patients. As control, 13 healthy subjects and 13 patients with other chronic B-cell leukemias were studied. In HCL patients with active disease, the percentage of CD4+ CD45R0+ T cells was significantly lower compared to healthy subjects (41% versus 57%, p = 0.01). Also the absolute numbers of CD4+ CD45R0+ T cells were reduced (396 x 10(6)/l versus 615 x 10(6)/l, p = 0.02) compared to healthy subjects, whereas within the CD8+ subset no differences were found. A contrasting elevation of percentages and numbers of CD45R0-expressing T cells (p < 0.0001) was seen in patients with chronic lymphocytic leukemia or leukemic non-Hodgkin's lymphoma. No relationship between CD4+ CD45R0+ and splenectomy, treatment with alpha-interferon or monocyte numbers was found in the HCL population. Despite the fact that the underlying mechanism of the reduced expression of CD45R0 in CD4+ T cells remains unclear, our observations may contribute to the understanding of an impaired T-cell functioning in HCL.