Cutaneous necrosis by cold agglutinins associated with glomeruloid reactive angioendotheliomatosis.

The cold agglutinin syndrome is a haemolytic disorder that can cause skin lesions, mainly on the acral areas, with acrocyanosis being the most frequent manifestation. Cutaneous necrosis due to cold agglutinins is very rare. Reactive angioendotheliomatosis (RAE) is an uncommon condition that exclusively affects the skin, characterized by a hyperplasia of endothelial cells and pericytes that can result in the formation of glomeruloid structures. The association of cold agglutinin syndrome with glomeruloid RAE has not been previously described. We report a 70-year-old man diagnosed as having a B-cell low-grade non-Hodgkin's lymphoma. He had two episodes of cutaneous necrosis in acral areas which were related to exposure to cold and due to IgM anti-I(T) cold agglutinins. Biopsy specimens showed vessel proliferations composed of dilated vascular spaces in the dermis and subcutis. Some vessel lumina were partially occluded by eosinophilic thrombi of fibrin and erythrocytes. Numerous closely packed capillaries were observed within pre-existing dilated vessels. This intravascular proliferation of capillaries displayed a glomeruloid pattern. We emphasize the possible presence of a cold agglutinin syndrome in patients with skin necrosis and findings of RAE with a glomeruloid pattern. Cold agglutinaemia may cause these distinctive histological changes.

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.

[Bone marrow autotransplantation in acute myeloblastic leukemia in its first complete remission. The clinical results in 41 patients]. / Autotrasplante de médula ósea en la leucemia aguda mieloblástica en primera remisión completa. Resultados clínicos en 41 pacientes.

BACKGROUND: A single-center experience using autologous bone marrow transplantation (ABMT) as postremission therapy for acute myeloid leukemia (AML) in first complete remission (CR1) in 41 patients is analyzed. PATIENTS AND METHODS: From July 1986 to March 1994, 41 patients with AML in CR1 underwent an ABMT. Source of hematopoietic stem cells was bone marrow in all cases. In eleven patients the marrow was purged with mafosfamide (ASTA-Z 7654). Median age was 31 years (17-59) and median time from CR to ABMT was 7 months (3-27). Busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) was employed as conditioning regimen in 36 patients. The rest 5 patients were prepared with cyclophosphamide (120 mg/kg) and fractioned total body irradiation (12 Gy). Eleven patients received G-CSF after AMBT because of an absolute neutrophil count lower than 0.5 x 10(9) on day +30. Survival analysis was performed according to the methods of Kaplan and Meier and comparison between groups used the log-rank test. RESULTS: With a median follow-up of 26 months (12-75) 21 patients remain alive in CR. Disease-free survival (DFS) at five years was 40% (95% CI: 25-55%). Transplant-related mortality, mainly for infection and hemorrhage, occurred in 6/41 patients (16%). Leukemia relapse was the main cause of treatment failure: 14/35 (40%). Probability of DFS and relapse was similar for those patients with purged ABMT on unpurged ABMT 45 +/- 23% vs 38 +/- 16% and 37 +/- 14% vs 54 +/- 22% respectively. A significantly longer engraftment time for neutrophils (> 0.5 x 10(9)) and platelets (> 20 x 10(9)) was observed in those patients who received a bone marrow treated with mafosfamide compared with the unpurged group (54 vs 29 days for neutrophils and 102 vs 58 for platelets respectively) (p < 0.05). CONCLUSIONS: ABMT is a feasible treatment for AML in CR1. Using bone marrow as hematopoietic stem cell support we observed that delayed engraftment was a common finding among AML patients, specially when the marrow was treatment with mafosfamide. Leukemia relapse remains as the main cause of treatment failure for ABMT.

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.

Busulfan and melphalan as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma.

Twenty-four patients with multiple myeloma (MM), three (12.5%) in complete remission (CR) and 21 (87.5%) in partial remission (PR) were treated with high-dose chemotherapy (HDCT) (busulfan 12 mg/kg+melphalan 140 mg/m2) as preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation. These cells were previously collected by leukapheresis after mobilization by high-dose cyclophosphamide (HD Cy)+rhGM-CSF (18 patients) or rhG-CSF alone (six patients). Considering 23 evaluable patients following HDCT, the CR rate was 58% (14 patients) and the PR rate was 38% (nine patients). One transplant-related death occurred following this regimen (4%). With a median follow-up of 20 months (range 4-34) after transplantation, 21 patients are alive (87%). Disease progression after transplantation was observed in four patients. Overall and relapse-free actuarial survival at 24 months was 91% and 74%, respectively. 12 patients (50%) remain in CR 15 months (4-34) post transplant. The major toxicity was mucositis. Busulfan+melphalan is a safe and feasible conditioning regimen for APBSCT in MM with acceptable toxicity and a high objective response rate, which may result in prolonged survival.

Erythropoietin in the treatment of delayed immune hemolysis of a major ABO-incompatible bone marrow transplant.

Delayed immune hemolysis can be observed after major ABO-incompatible bone marrow transplants (BMT). The management of these hemolytic episodes includes transfusion of group O red blood cells and increases of immunosuppression. Here we report the case of a 25-year-old patient who developed overt immune hemolysis on day +50 after a HLA-identical ABO-incompatible BMT. To avoid added immunosuppression, erythropoietin was started: an increase in reticulocytes sufficient to maintain hemoglobin despite persistent hemolysis was observed. We conclude that erythropoietin may have a role in the management of delayed-onset hemolysis of major ABO-incompatible BMT, especially when added immunosuppression is undesirable.

Fractionated TBI and methotrexate-cyclosporin do not seem to increase relapses in BMT for first chronic phase CML patients: results of a single centre study.

Fractionated total body irradiation (FTBI) and methotrexate-cyclosporin A(MTX-CSA) have been found useful in reducing interstitial pneumonia (IP) and acute graft-versus-host-disease (GVHD) in bone marrow transplantation patients, but an increase in relapse rate has been observed by some authors when these strategies are used. To evaluate this relapse risk, we performed a retrospective analysis in 24 consecutive first chronic phase chronic myeloid leukemia patients who received an HLA-identical non-T cell-depleted graft in a single institution. All were conditioned with cyclophosphamide plus FTBI (12 Gy in six fractions delivered twice daily for 3 days) (CY-FTBI) and received MTX-CSA as GVHD prophylaxis. Serial hematologic and cytogenetic bone marrow analysis were performed at least three times (days +30, +100, +360) and at variable intervals thereafter in long-term survivors. Actuarial probabilities of developing IP and acute GVHD greater than or equal to II were respectively 5.9% and 44.2%, with a GVHD-associated mortality of 33%. Four-year actuarial relapse and disease-free survival rates were 7.7% and 48.2% respectively. No exclusively cytogenetic relapses were observed. Our results suggest that CY-FTBI and MTX-CSA are not associated with an increase in relapse rate in 1CP-CML patients.

[Critical analysis of the routine use of the direct antiglobulin test in 22,517 cross-matching tests]. / Análisis crítico del empleo rutinario de la prueba de la antiglobulina directa (DAT) en 22,517 pruebas cruzadas.

Routine performance of the direct antiglobulin test (DAT) in pretransfusion testing (PT) is controversial. To evaluate its usefulness, we review the positive DATs found in 22,517 PT performed in our center in the last five years. DAT was positive in 330 PT (1.4%). Eluate studies gave information, not obtained from the rest of PT, in 6 cases. DAT predictive value is low (1.8% of the positive DATs, 0.02% of all PT). Although this predictive value is low, we keep on follow including DAT in PT but we have reduced eluate studies to 1) positive DAT of untransfused patients (to get information of the DAT prior to transfusion and to detected autoimmune haemolytic anaemias) and 2) positive DAT of previously transfused patients with previous negative DAT or changes in its reactivity (for the prompt detection of clinically significant antibodies).