Atypical IgM multiple myeloma with deletion of c-MAF.

IgM multiple myeloma (MM) is a rare subtype of myeloma that shares clinical and pathological features with Waldenström's macroglobulinaemia. These are two separate entities that differ both in therapy and prognosis. We report a 57-year-old male, who presented with anaemia, hypercalcaemia, acute renal failure and several vertebral fractures that clinically suggested a multiple myeloma. Further investigations revealed a serum monoclonal component of IgM lambda type and a bone marrow infiltrated by small, lymphoplasmocytic cells. IgM MM was finally diagnosed by means of both inmunophenotypic and immunohistochemistry techniques, stressing the importance of inmunophenotypic evaluation when clinical and morphological features are discordant. Fluorescence in situ hybridization (FISH) studies disclosed a particular combination of deletion 13q14, t(11;14) and monoallelic deletion C-MAF without t(14;16). The clinical evolution after a Bortezomib-containing polychemotherapy and autologous stem cell transplantation (ASCT) conditioned with busulphan and melphalan is also presented. This very uncommon case highlights the impact of immunophenotyping on the differential diagnosis between IgM MM and WM, to choose the best treatment and establish an appropriate outcome.

Evaluation of CD7 and terminal deoxynucleotidyl transferase (TdT) expression in CD34+ myeloblasts from patients with myelodysplastic syndrome.

There is an emerging use of flow cytometry to evaluate patients with myelodysplastic syndrome (MDS). We have studied CD7 and TdT expression in the CD34+ myeloid blast cell population in 55 bone marrow samples of patients with MDS. CD7 and/or TdT were detected in 38 out of 55 patients (69%). CD7 expression was not related to other bad prognosis data but conversely, we found an association between TdT+ CD34 myeloblasts and high-risk MDS patients according to the International Prognostic Scoring System. Therefore, CD7 and TdT may help to establish the diagnosis of MDS and, TdT expression also seems to be a useful marker in distinguishing risk groups.

[Non-Hodgkin's lymphoma and urinary tract. About a case reported]. / Linfoma no Hodgkin y aparato urinario. A propósito de un caso.

We pass to describe a case of non Hodgkin's secondary lymphoma with metachronic affectation in bladder and left kidney, in a patient with different extranodals locations. Both in bladder and kidney, it was a low grade lymphoma type B with centrofolicular cells. We suggest haematogenous dissemination and affinity of lymphomatous clone to the urinary tract. We establish some diagnostic considerations, such about the therapeutic management in this type of pathologies.

Linfoma no Hodgkin y aparato urinario. A propósito de un caso / Non-Hodgkin´s lymphoma and urinary tract. About a case reported

Describimos un caso de linfoma secundario no Hodgkin con presentación metacrónica en vejiga y riñón izquierdo, en un paciente con diferentes afectaciones extragonadales. Tanto en la vejiga como en el riñón se trataba de un linfoma de bajo grado tipo B de células centrofoliculares. Se sugiere la diseminación hematógena y afinidad del clon linfomatoso por el aparato urinario. Se establecen algunas consideraciones diagnósticas, así como sobre el enfoque terapéutico en este tipo de patologías (AU)

We pass to describe a case of non Hodgkin’s secondary lymphoma with metachronic affectation in bladder and left kidney, in a patient with different extranodals locations. Both in bladder and kidney, it was a low grade lymphoma type B with centrofolicular cells. We suggest haematogenous dissemination and affinity of lymphomatous clone to the urinary tract. We establish some diagnostic considerations, such about the therapeutic management in this type of pathologies (AU)

Long-term management of homozygous protein C deficiency: replacement therapy with subcutaneous purified protein C concentrate.

We present the case of a full-term newborn in whom purpura fulminans developed shortly after birth. A diagnosis of homozygous protein C deficiency was established based upon undetectable plasma protein C activity and antigenemia in the newborn infant, and was later confirmed by protein C gene analysis. Specific replacement therapy with intravenous protein C concentrate was started 9 days after birth. This rapidly led to the complete regression of cutaneous lesions and consumption coagulopathy. After stabilization, oral anticoagulation was initiated in association with prophylactic treatment with intravenous protein C concentrate. However, oral anticoagulation was finally abandoned as the patient presented several thrombotic and hemorrhagic episodes clearly related to difficulties with anticoagulation. Due to the hazards related to prolonged venous access, we are currently using subcutaneous infusion of protein C concentrate for the long-term management of this condition, with satisfactory results.

[Outcome of 70 patients diagnosed with Hodgkin's disease after first-line and salvage treatment: experience at one center]. / Evolución de 70 pacientes diagnosticados de enfermedad de Hodgkin tras tratamiento de primera línea y de rescate: experiencia de un centro.

BACKGROUND: Retrospective analysis of 70 patients with Hodgkin's disease (HD) and treated consecutively in our center between 1979 and 1993. PATIENTS AND METHODS: All ganglionar biopsies were reviewed and finally 60 patients were selected: 43 males and 17 females with a median age of 39 years (12-79) and the following features: 55% III-IV stages, 25% extranodal involvement, 32% bulky mediastinum and 57% B-symptoms. Scheme of treatment: Only radiotherapy in 9 patients with localized stages and no adverse factors; only chemotherapy in 25 with advanced stages and combined therapy in 15 with localized stages and any adverse factor and in 7 with advanced stage and bulky disease. Chemotherapy was mainly based on MOPP until 1987 and MOPP/ABVD afterwards. Only four patients did not follow this scheme: 2 due to progression, 1 due to toxicity and 1 due to medical decision. RESULTS: Fifty patients achieved complete remission (CR), 2 partial and 8 minimal response or progression under therapy. Eleven patients have died: 6 due to HD, 4 of second neoplasias and 1 of an opportunistic infection. With a median follow-up for surviving patients of 4.8 years (1-2), the estimated overall survival at 8 years is 67.7% (SD 9%), tumor mortality 82.6% (SD 7%) and progression free survival 66.7% (SD 7%). Disease free survival for CR patients is 78.4% (SD 9%). Response to treatment was the only factor significantly associated with survival (p = 0.0001). The estimated survival for CR patients who relapsed is 92.3% versus 28% for those who did not obtain a CR (p = 0.0001). CONCLUSION: In our experience, first line therapy adjusted to clinical features at diagnosis has good results. Response to treatment has been the determinant factor for survival, mostly because salvage treatments, including high-dose chemotherapy approaches, have been of little effectiveness.

Unexpected late graft failure 9 months after HLA-identical bone marrow transplant (BMT) for chronic myeloid leukemia (CML): treatment with a second BMT.

We describe a patient with CML in 1st chronic phase (CP) who experienced a graft failure 9 months after an HLA genotypically identical sibling BMT. Drug toxicity, viral infections, chronic graft-versus-host-disease (GVHD) or leukemic relapse were excluded. Chimerism study showed 85% of donor marrow cells. She underwent a second BMT, reengrafted but died of grade IV acute GVHD.

Autologous stem cell transplantation (ASCT) for poor prognostic Hodgkin's disease (HD): comparative results with two CBV regimens and importance of disease status at transplant.

Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT in our Department was analyzed retrospectively. Median age was 28 years (28 males and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse) and two had primary refractory disease. The CVB regimen with two different schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300 mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY 7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28 evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2 years, actuarial overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%, with a median follow-up for the surviving patients of 3 years (0.7-7.6). No differences in these survival functions according to the CBV regimen used were observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1 year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of extranodal disease at transplant (P=0.01), and a CR status at transplant (P=0.0006) were associated with a better PFS on univariant analysis. On multivariate analysis, only CR status at transplant remained significant (P=0.05). When patients in second CR at transplant and those in first sensitive relapse were analyzed separately, no differences in clinical characteristics or in treatment received pretransplant were observed; however, PFS was significantly different (P=0.01). In conclusion, CR status at transplant is useful in identifying 'good risk' patients and is necessary to obtain the greatest benefit from ASCT independent of the CBV regimen used.

Comparison of peripheral blood progenitor cell mobilization in patients with multiple myeloma: high-dose cyclophosphamide plus GM-CSF vs G-CSF alone.

The best method for peripheral blood progenitor cell (PBPC) mobilization in patients with multiple myeloma (MM) remains controversial. We report the results of two different methods of PBPC collection for autologous transplantation in 40 patients with stage II or III MM. In group I (n = 18), HD-CY, 4 g/m2 i.v., was administered followed by GM-CSF, 8 microg/kg/day s.c., until the end of collection, starting the leukaphereses after hematological recovery (>1 x 10(9)/l WBC). In group II (n = 22), G-CSF, 10 microg/kg/day s.c., was used alone until the last day of collection, starting consecutive aphereses on the 5th day. A minimum of two aphereses were performed to collect at least 2 x 10(6)/kg CD34+ cells. Both patient groups were comparable for age, sex and clinical prognostic features as well as previous therapies. In group I, the median yields per pheresis were: MNC 1.47 (1.38-2.32) x 10(8)/kg, CFU-GM 0.82 (0.18-13.2) x 10(4)/kg and CD34+ cells 1.98 (0.96-6.96) x 10(6)/kg. In group II these results were: MNC 2.44 (2.06-3.6 x 10(8)/kg) (P = 0.03), CFU-GM 0.75 (0.16-7.8) x 10(4)/kg and CD34+ 1.05 (0.32-3.4) x 10(6)/kg (P = 0.02). The median number of aphereses performed in each group was 5 (4-12) with a median of 5.24 +/- 2.51 in group I and 3 (2-6) with a median of 3.1 (+/- 0.91) in group II (P = NS). Hospitalization for PBPC mobilization was required in all patients in group I and the treatment-related toxicity was greater in this group: 12 patients (66%) developed fever requiring antibiotics during the neutropenic period after HD-CY and six (33%) patients required transfusion support. After receiving busulfan 12 mg/kg p.o. and melphalan 140 mg/m2 i.v., as the conditioning regimen, the median periods to reach granulocytes (>0.5 x 10(9)/l) and platelet (>20 x 10(9)/l) engraftment were 12 and 11 days respectively (ranges 8-20 and 10-16) in group I (HD-CY plus GM-CSF group), and 11 and 13 days respectively (ranges 7-42 and 10-38) in group II (G-CSF group) (P = NS). In conclusion, these data suggest that although HD-CY plus GM-CSF is superior to G-CSF alone based on mean CD34+ cell yield per pheresis, adequate CD34+ cell collections can be achieved with G-CSF alone in most MM patients with less toxicity and with simplification of the procedure.

Quinton-Mahurkar catheter as short-term central venous access for PBSC collection: single-center experience of 370 aphereses in 110 patients.

We retrospectively analyzed our experience with the Quinton-Mahurkar dual-lumen hemodialysis catheter as short-term central venous access for harvesting peripheral blood stem cells (PBSC) for autologous transplantation. For intensification therapy for various malignancies 370 leukaphereses were performed in 110 candidates. The catheter was placed percutaneously under local anesthesia only for the time of blood collection and in no case was it used for the PBSC transplant. No systemic antithrombotic prophylaxis was administered. PBSC were collected using a continuous flow cell separator, COBE Spectra, after mobilization with chemotherapy followed by cytokine: rhGM-CSF and rhG-CSF s.c. (35 patients) or rhG-CSF s.c. alone (75 patients). The median number of aphereses was two (1-13). Eighty-nine patients (81.3%) required three or fewer sessions to collect the minimum mononuclear cell target number of 6 x 10(8) MNC/kg. The volume of blood per kg body weight processed for each apheresis was 240 ml (range 150-560 ml) equivalent to 13 l (6-30 l) and the median flow rate was 61 ml/min (range 30-90 ml/min). The total CD34+ cell yield per patient was 3.55 x 10(6)/kg (0.26-34.8) and the MNC yield was 6.1 x 10(8)/kg (2.96-12.6). We observed the following complications: local infection in four cases (3.6%), catheter occlusion for local thrombosis in two cases (1.8%) and pneumothorax in one case (0.97%). In our experience the Mahurkar-Quinton catheter, when placed specifically for apheresis sessions, was very effective and safe for PBSC harvesting with a low incidence of complications.

Clinical results of a stringent policy on prophylactic platelet transfusion: non-randomized comparative analysis in 190 bone marrow transplant patients from a single institution.

The threshold for prophylactic platelet transfusion remains controversial. Usually the decision is based on arbitrary numerical criteria. The classical 20 x 10(9)/l trigger could be safely reduced with considerable benefits. Few studies have evaluated the clinical impact of stringent policies. We have performed a retrospective analysis comparing major haemorrhages during hospitalization in 190 patients undergoing BMT in two different periods. In 87 patients transplanted from 1990 to 1991, the 20 x 10(9)/l trigger was used for prophylactic platelet transfusion. In 103 other patients transplanted from 1993 to 1994, we adopted a stringent prophylactic policy: < 10 x 10(9)/l for stable patients and < 20 x 10(9)/l when higher platelet consumption factors were present. In the stringent group, 12 patients presented 13 major haemorrhages and four died from haemorrhage. In the classical group 12 patients presented 14 major haemorrhages and three died from haemorrhage. Platelet consumption factors were present in 12 of 13 haemorrhages in the stringent group and in 12 of 14 in the classical group. By contrast, stable patients presented less haemorrhages (2/14 and 1/13, respectively). A statistically significant reduction in the use of platelet units was observed when comparing both groups: the median of platelet units administered in the first 100 days of transplant was 73 (3-943) and 54 (0-647) in the classical and in the stringent group, respectively (P < 0.01); and the median of platelet units received per day was 0.8 (0.03-30) and 0.5 (0-6.94) (P < 0.01). Our results emphasize the safety of a stringent prophylactic platelet transfusion policy after BMT, reducing the overall use of platelet transfusions. Further studies are necessary to confirm these results and to define optimal transfusion strategies.

Large-volume leukapheresis for peripheral blood stem cell collection in children: a simplified single-apheresis approach.

Large volume leukapheresis (LVL) defined as the processing of greater than three volumes of blood in a single session for peripheral blood stem cell (PBSC) collection was performed in 27 children, aged from 1 to 15 years, with various malignancies. Harvesting of PBSC was started after 4 days of cytokine (G-CSF 12 micrograms/kg s.c.) alone. With the exception of two cases the rest (92.5%) needed only a single apheresis to yield the minimum number of cells required for transplantation. No consistent side-effects were observed and the LVL were well tolerated by children. An average of 7.6 x 10(8) MNC/kg, 6.1 x 10(6)/kg CD34+ and 2.1 x 10(4)/kg CFU-GM were harvested. To date, 19 patients have been transplanted after myeloablative treatment and sustained engraftment was achieved in all cases. LVL can be safely and easily performed in children allowing adequate PBSC collection for transplantation with prompt hematological engraftment.

Gelatinous degeneration presenting as a preleukaemic syndrome.

Gelatinous degeneration of marrow is a rare histological disorder associated with chronic debilitating diseases, such as anorexia nervosa, AIDS and postchemotherapy aplasia. Solid tumours have been associated with this condition but it has been reported in only two patients with leukaemia. In these cases leukaemia and gelatinous degeneration were diagnosed simultaneously. In the case reported here, a 48 year old man, gelatinous degeneration was the only histological finding observed more than two years before the diagnosis of acute myelogenous leukaemia with monosomy 7. The significance of hyaluronic acid deposition remains uncertain. Two hypotheses have been put forward: (1) that gelatinous degeneration occurs during tissue repair; and (2) that gelatinous degeneration inhibits haemopoiesis by altering the microenvironment of the bone marrow. In the case reported here, the presence of monosomy 7 suggests that myelodysplasia was the underlying disorder which finally evolved into acute leukaemia.