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We have used a novel method to conduct non-myeloablative stem cell transplantation (NST), making the following changes in previous methods: Use of the cheapest conditioning drugs, tailored number of apheresis sessions in the donors, elimination of ganciclovir and IgG, outpatient conduction when possible, diminished number of transfusions of blood products and diminished number of donor lymphocyte infusions. With this method, we have prospectively conducted 70 allografts in patients with different diseases: Chronic myelogenous leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplasia, thalassemia major, relapsed Hodgkins disease, Blackfan-Diamond syndrome and aplastic anemia. In them, the median granulocyte recovery time to 0.5 x 10(9)/L was 11 d, whereas the median platelet recovery time to 20 x 10(9)/L was 12 d. Twenty patients did not need red blood cell transfusions and 17 did not need platelet transfusions. In 55 individuals (78%), the procedure could be completed fully on an outpatient basis. Follow-up times range between 30 and 800 d.: Four patients failed to engraft and recovered endogenous hemopoiesis; 16 patients (23%) developed acute graft versus-host disease (GVHD) whereas 28 (49%) developed chronic GVHD. Thirty two patients (47%) have died: 21 with a relapsing disease and seven as a result of GVHD; the median post-trasplant survival (SV) was 420 d., whereas the 12-mo. SV was 42%. The 100-day mortality was 3.8% and the transplant-related mortality was 14.2%. The median cost of the allografts was 18,000.00 US dollars. This method could be particularly adequate in developing countries, where very few individuals can afford the cost of a conventional bone marrow transplantation procedure.

During an 18-month period, 10 consecutive Mexican mestizos with a dinical marker associated with a primary hypercoagulable state were studied. The assessment of the sticky platelet syndrome (SPS) was done by the method described by Mammen. In addition, the activated protein C resistance phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen activator inhibitor type 1, IgG and IgM isotypes of anti-phospholipid antibodies, homocysteine levels, the factor V gene Leiden mutation, the 677 C->T mutation in the 5,10-methylen-tetrahydrofolate-reductase (MTHFR), and the G20210A polymorphism in the 3'-untranslated region of the prothrombin gene were studied. Six patients with the SPS were identified: only one displayed this as the single thrombophilic abnormality; in five others, additional thrombosis-prone conditions were found: heterozygosity for the MTHFR 677 gene mutation in five cases; and, in one case each, heterozygosity for the factor V Leiden mutation, heterozygosity for the factor II G20210A mutation, and antiphospholipid antibodies in another. Four of the six patients had a family history of thrombophilia. All patients were treated with aspirin and no new vasoocclusive episodes have been recorded. SPS in not an infrequent finding in Mexican mestizo thrombophilic patients and may contribute to thrombophilia.

Thirty consecutive patients were given non-myeloablative stem cell transplants (NST) and posttransplant chimerism was studied by several methods. In 16 individuals definitive proofs of chimerism have been shown: In 10 cases sex chimerism, in 7 cases chimerism shown by means of microsatellites, in 4 cases ABO chimerism, in two cases Rh chimerism and in one HLA-DR chimerism. In addition, in 9 individuals the disappearance of the molecular marker of the leukemia is an indirect evidence of the chimerism, as well as the presence of graft versus host disease (GVHD) in 17 allografted patients. Only in 6 patients no evidence of chimerism could be shown; all of them died as a result of either persistent or relapsing malignancy. Since the early patterns of chimerism may be predictive of either GVHD or graft loss in NST and, since therapeutic intervention (such as donor lymphocytes infusions) is based in the patterns of chimerism, it is possible that chimerism studies in these types of allografts should be ideally done more frequently than in conventional allotransplants.

Background: The chronic myeloproliferative diseases (CMPDs) include chronic myelogenous leukemia (CML), primary (essential) thrombocythemia (PT), agnogenic myeloid metaplasia (AMM), and polycythemia vera (PV). Certain hematological malignancies have a different prevalence in our country than in countries with Caucasian populations. Data indicate that the prevalence of CML in our country is similar to that found in Caucasians; however, the prevalence of the other CMPDs has not been studied., Methods: In a total of 8069 individuals studied between June 1983 and March 2001 in the Centro de Hematologia y Medicina Interna de Puebla, we assessed the prevalence of CML, PT, AMM, and PV. Some of the clinical features of these individuals were also assessed., Results and Conclusions: Forty-nine patients with CML, 14 with PT, 7 with AMM, and 3 with PV were identified. The clinical presentations of these CMPDs were not different from those described in Caucasians., Conclusions: We found that CML was more than 3 times more frequent than PT, that both PV and AMM were exceptional, and that PT, AMM, and PV were significantly less frequent in Mexican than in Caucasian populations (P < .01).

Using a nonmyeloablative, immunosuppressive, fludarabine (FLU)-base conditioning regimen, we have performed allogeneic peripheral blood stem cell transplants in 17 patients (six with chronic granulocytic leukemia, four with acute myelogenous leukemia, five with acute lymphoblastic leukemia, one with myelodysplasia and one, with thalassemia major). Conditioning regimen consisted of FLU/busulfan/cyclophosphamide or FLU melphalan. To avoid graft vs. host disease (GVHD), cyclosporine and methotrexate were used. Median granulocyte recovery time to 0.5 x 10(9) was 11 days, whereas median platelet recovery time to 20 x 10(9) was 12 days. Seven patients did not need red blood cell transfusions and four did not need platelet transfusions. In thirteen individuals (76%), the procedure could be completed fully on an outpatient basis. Follow-up times range between 1 and 14 months. Five of 17 patients developed acute GVHD whereas 4/10 developed chronic GVHD. The 14-month survival (SV) is 70% and median SV is not reached. Five patients (29%) have died, three due to relapse of the disease and two due to GVHD. The transplant-related mortality was 5.8%. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and may represent another approach in management of patients requiring allogeneic stem cell transplant.

Cytomegalovirus (CMV)-related deaths and data of clinically evident CMV disease were assessed in a group of 47 individuals given allogeneic non-myeloablative hematopoietic stem cell transplants (NST). IgG anti-CMV antibodies were found in 56% of the donors and 76% of the receptors. Prophylactic ganciclovir was given to only 12 of the recipients during 100 days after the graft. There were no CMV-related deaths and clinically overt CMV disease was not found in any individual. The follow up post-transplant period of the patients, ranges between 30 and 810 days (median 242 days), the actuarial median survival (SV) is above 810 days and has not been reached, whereas the 810-days SV is 60%. Eighteen patients (38%) died 30-480 days after the transplant; four failed to engraft and died because of progressive disease; three died as a consequence of graft versus host disease (GVHD), whereas eleven individuals had a relapse of the malignancy and died. It is possible that the reduced bone marrow damage during NST, the prompt recovery of both the hematopoiesis and immune function in this type of allografts and the use of peripheral blood hematopoietic stem cell (HSC) is responsible for the absence of CMV-related deaths and clinical disease despite a high prevalence of CMV infection in these individuals.

Background: The prevalence of beta-thalassemia in Mexico is not known in detail., Methods: Data of studies investigating abnormal hemoglobins between September 1987 and November 2000 were analyzed; in addition, data of red-blood-cell indices and clinical features were analyzed in patients identified as carriers of beta-thalassemia., Results: In 1,639 prospective studies looking for abnormal hemoglobins, 429 disclosed some abnormality; of these, 319 cases displayed abnormally high levels of hemoglobin A2, thus consistent with the diagnosis of beta-thalassemia. This hemoglobin abnormality represented 74.2% of all abnormalities, both quantitative and qualitative, of the molecule of hemoglobin. There were 317 heterozygotes and only two homozygotes. We have previously shown that the most frequent cause of anemia as the iatrotropic condition in Mexican mestizos is iron deficiency. We found that iron deficiency is 11.5 times more frequent than beta-thalassemia and that the latter is 1.3 times more frequent than macrocytic/megaloblastic anemia., Conclusions: beta-thalassemia should not be considered as infrequent in Mexico, and individuals with red blood cell microcytosis and/or hypochromia with or without anemia should be screened for thalassemia.

The features of the engraftment in 26 patients allografted using reduced-intensity conditioning regimen (8 with chronic myelogenous leukemia, 6 with acute myelogenous leukemia, 9 with acute lymphoblastic leukemia, 1 with hybrid acute leukemia, 1 with myelodysplasia and 1 with thalassemia major) were analyzed. Patients received a median of 10 x 10(8)/Kg mononuclear cells (range 1.6 to 22.9), and a median of 4.2 x 10(6)/Kg CD34 cells (range 0.3 to 14). There was a linear correlation between the number of infused mononuclear cells (MNC) and that of CD34 cells (r = 0.78, p = 0.002). Three patients (11%) failed to engraft; in those who engrafted, the median time to achieve > 500 granulocytes was 11 days (range 10 to 22), and the median time to achieve > 10,000 platelets was 12 days (range 10 to 41). The three patients who failed to engraft received less than 5 x 10(8)/Kg MNC (1.6, 4.6 and 4.9) and less than 0.5 x 10(6)/Kg CD34; however, five of eight patients who received less than 5 x 10(8)/Kg MNC still engrafted successfully. On the other hand, all the patients who received less than 0.5 x 10(6)/Kg CD34 cells failed to engraft. Within the group of patients who engrafted, it was found that those who received more than 7 x 10(6)/Kg CD34+ cells tended to earlier recover > 20 x 10(9)/L platelets (p = 0.02), and > 0.5 x 10(9)/L neutrophils (p = 0.06) before day 15, than those who received less than 7 x 10(6)/Kg CD34+ cells. No such association could be established between the number of MNC and the time for recovery. In these patients allografted using reduced-intensity conditioning regimens, the target doses of hematopoietic cell used were similar to those described for conventional allografts: The number of CD34 infused cells was significantly related to the possibility of failure to engraft and to the recovery rate of the hemopoiesis.

Background: The molecular follow-up of patients with chronic myelogenous leukemia (CML) has been described as useful in other countries, but there are not data reported in Mexico., Methods: All patients studied at Laboratories Clínicos de Puebla/Centro de Hematología y Medicina Interna de Puebla in which the BCR-ABL hybrid gene was identified by means of polymerase chain reaction were analyzed. In 22 individuals the molecular marker of the disease was studied at diagnosis and in different instances afterwards; these patients were treated with chemotherapy, interferon, autologous or allogeneic bone marrow transplantation., Results: Only the six patients that were allografted from HLA-identical siblings cleared the molecular marker of the disease; the rest of them did not achieve molecular remissions. The median survival (SV) of the whole group has not been reached, whereas the 53-month SV is 68%. One of the allografted patients died as a result of complications of graft versus-host disease., Conclusions: We have found useful the molecular monitoring of the treatment of patients with CML. Using this approach, we found that molecular remissions can be accomplished only with allografting; however, other therapeutic approaches may also result in long-lasting hematologic remissions.

Using nonmyeloablative, immunosuppressive, fludarabine (FLU)-based conditioning regimens, we have performed allogeneic peripheral blood stem cell transplants in 26 patients (8 with chronic myelogenous leukemia, 6 with acute myelogenous leukemia, 10 with acute lymphoblastic leukemia, 1 with myelodysplasia, and 1 with thalassemia major). Conditioning consisted of FLU/busulphan/cyclophosphamide/cyclosporin-A (CyA)/methotrexate, or FLU/melphalan/CyA/methotrexate. The median granulocyte recovery time to 0.5 x 10(9)/l was 11 days, whereas the median platelet recovery time to 20 x 10(9)/l was 12 days. Twelve patients did not need red blood cell transfusions, and 8 did not need platelet transfusions. In 21 individuals (81%), the procedure could be completed fully on an outpatient basis. Follow-up times range between 30 and 600 days: one patient failed to engraft and recovered endogenous hemopoiesis; six out of 26 patients developed acute graft-versus-host disease (GVHD) whereas 7/22 developed chronic GVHD. Twelve patients (46%) have died, nine of them with a relapsing disease and three with GVHD; median post-transplant survival (SV) was 300 days, whereas the 12-month SV was 42%. The 100-day mortality was 3.8% and the transplant-related mortality was 11.5%. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and it may represent another approach in the management of patients requiring an allogeneic stem cell transplant., (Copyright 2001 Wiley-Liss, Inc.)

Heterozygosity for beta-thalassemia (minor) by itself does not lead into iron overload; however, when it is inherited together with a homozygous state for either the H63D or the C282Y mutations of the hereditary hemochromatosis gene (HFE gene), iron overload may ensue. We describe here a kindred in which the propositus, being heterozygote for beta-thalassemia and the H63D mutation of the HFE gene, developed severe iron overload and in turn, chronic liver failure with portal hypertension. Other members of the family with either beta-thalassemia or heterozygous for the H63D gene mutation did not develop iron overload. The interaction between beta-thalassemia and hereditary hemochromatosis is briefly discussed and speculations about other possible genetic mutations leading into familial iron loading are done.

We have shown that in Mexican mestizo patients with clinical features of primary thrombophilia, 39% have activated protein C resistance phenotype, 5% protein C deficiency, and 2% protein S deficiency. In the present study, in a group of 37 thrombophilic Mexicans and 50 normal controls, we assessed the factor V G1691A (Leiden), the prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms. Four patients were found to be heterozygous for factor V Leiden, 5 heterozygous for the prothrombin 20210, 16 heterozygous, and 6 homozygous for the MTHFR 677. There were four individuals with co-segregation of alleles: two heterozygotes for the factor V Leiden/prothrombin 20210, one heterozygote for prothrombin 20210/MTHFR 677, and one heterozygote for prothrombin 20210/homozygote for MTHFR 677. For factor V Leiden, prothrombin 20210, and MTHFR 677 mutations, the allele frequencies were respectively 1% (+/-0.2%, alpha = 0.05), <1% and 51% (+/-5%, alpha = 0.05), with calculated relative risks for thrombosis of 5.94 (P = 0.08), >7.66 (P < 0.05), and 0.44 (P NS), respectively. In Mexican mestizo thrombophilic patients, the low prevalence of the factor V Leiden mutation (10.8%) and the high prevalence of the prothrombin 20210 mutation (13.5%) contrast with those identified in Caucasian thrombophilic patients (21% and 6%, respectively; P < 0.01). On the other hand, the high prevalence of the MTHFR 677 mutation gene both in normal controls (78%) and thrombophilic patients (61%) does not support a role of this mutation in the thrombogenesis of Mexican mestizo patients.

Indirect evidence of hemolysis has been described in patients with autoimmune thrombocytopenic purpura. In order to collect more data, another method to assess red blood cell destruction in these patients was employed: measurement of free haptoglobin levels. In 17 individuals with autoimmune thrombocytopenic purpura the levels of free haptoglobins were assessed after carefully ruling out microangiopathic hemolysis, systemic lupus erythematosus or overt Evans syndrome. Abnormally low levels of free haptoglobins were found in five individuals (29%) as indirect evidence of hemolysis. The long-term thrombocytopenia-free status was lower in patients with low haptoglobin levels than in those with normal levels (40 versus 58%). These data, added to previous evidence, support the observation of Evans made 50 years ago: "there is a spectrum-like relationship between primary thrombocytopenia and haemolytic anemia".". Accordingly, the concept of "attenuated" variants of the Evans syndrome could be entertained.

Along a 17-year period 7,373 patients were prospectively studied in a private practice Health facility; of these 11 were patients with Waldenström's macroglobulinemia; calculations from these data and previous publications show that this lymphoid malignancy represents in Mexico 0.18% of all hematologic malignancies, a figure 11 times lower than that described from caucasians. The median age was 65 years (range 31 to 84); there were 6 males and 5 females. Ten individuals were mexican mestizos, whereas one had a caucasian phenotype. The clinical features of the patients afflicted by the disease in Mexico were similar to those reported from caucasian populations. The median survival (SV) of the group of patients was 40 months, whereas the 42-month survival was 49%; the prognosis of the disease was relatively good despite the fact that complete remissions were unfrequent as a result of the treatment.

Background: The prevalence of hereditary hemochromatosis (HH) (H63D/C282Y) gene variants in Mexico is unknown., Methods: Using amplification refractory mutation system polymerase chain reaction, an analysis of HFE-codon 63/282 (H63D/C282Y) gene variants was performed in a group of 153 Mexican mestizo blood donors and six individuals with familial iron overload., Results: In normal blood donors, three heterozygotes for the C282Y mutation (2.0%) were found, whereas 18 heterozygotes and one homozygote for the H63D mutation (11.8% and 0.6%, respectively) were identified; there was one compound heterozygote for the C282Y/H63D mutation. These data resulted in allele frequencies of 0.013 (+/-0. 2%, alpha = 0.05) and 0.062 (+/-0.9%, alpha = 0.05), respectively, for these two mutations, results similar to those found in whites. In the six patients with the HH phenotype, two were found to be heterozygous for C282Y and one heterozygous for H63D; three individuals with HH had no gene mutations. Two heterozygous HH individuals were found to have iron overload associated with other conditions: one heterozygous for C282Y infected with HIV, and another heterozygous for H63D with heterozygous beta-thalassemia., Conclusions: The prevalence of C282Y and H63D HFE gene mutations in Mexican mestizos is similar to that found in other populations. In addition, other gene mutations responsible for HH in the Mexican mestizo population should be investigated, because, in three of six individuals with the HH phenotype, neither of the two mutations was recorded.

Along a 5-year period in a single institution, specific molecular markers were prospectively looked for in consecutive patients with acute leukemia, by means of polymerase chain reaction (PCR): In patients with acute lymphoblastic leukemia (ALL), the BCR/ABL and TEL-AML1 fusion transcripts as well as clonotypic immunoglobulin gene rearrangements were investigated, whereas in patients with acute myelogenous leukemia (AML) the PML-RAR alpha, AML1-ETO and CBF beta-MYH11 fusion proteins were assessed. Specific molecular markers were identified in 15/75 patients: Four with ALL (three with clonotypic IgG rearrangements and one with BCR/ABL) and 11 with AML (nine with the PML/RAR alpha fusion protein--M3 AML-, and two with the AML1/ETO fusion protein--M2 AML-). During follow-up periods ranging from 1 to 60 months, seven patients cleared the residual disease assessed by PCR (RD-PCR), whereas eight patients had either persistence of RD-PCR or a molecular relapse. For patients without or with RD-PCR, the 30-month survival (SV) was 86% and 14%, respectively, whereas median SV was > 60 and two months, also respectively (p < 0.01). Six of eight patients with detectable RD-PCR died, all of them within three months after the detection of the RD-PCR, whereas two of the patients that relapsed were rescued with treatment and entered a second molecular remission. Two of the three molecular relapses were detected without an overt morphological relapse. It is concluded that PCR is a valuable method for assessing residual disease and that early diagnosis of relapses may lead into effective salvage treatment in some instances.

The case of an adult with PML/RARalpha(+) hypergranular acute promyelocytic leukemia (M3) that evolved into a rapidly fatal M3 acute myelocytic leukemia without PML/RARalpha after a complete and molecular remission had been achieved, is presented. Only 7 such cases have been published in the literature. The possible origin of this either leukemic relapse or secondary malignancy is briefly discussed, focusing on the fact that this diagnosis could only be defined by adequate molecular biology studies in the leukemic cells.

The results of the treatment of 43 patients with acute promyelocytic leukemia (PML) are reported: 27 were treated initially with all-trans-retinoic acid (ATRA), whereas 16 were treated with conventional chemotherapy. All patients received myelosuppressive chemotherapy after the initial treatment. Respectively, the complete remission rate was 92% and 37% (P < 0.01), the 5-day mortality rate was 0% and 44% (P < 0.001), and the 28-day mortality rate was 4% and 44% (P < 0.001). The median disease-free survival was 12 and 1 months (P < 0.01), whereas the 12-month disease-free survival was 50% and 13% (P < 0.01) and the 36-month disease-free survival was 41% and 9% (P < 0.01). Thirteen of the patients treated with ATRA were given the treatment fully as outpatients. ATRA given as initial therapy decreased significantly early mortality in promyelocytic leukemia patients; because some promyelocytic leukemia patients given ATRA as initial therapy can be treated as outpatients, the costs of this treatment modality may be diminished., (Copyright 1999 Wiley-Liss, Inc.)

Background: Methods to simplify bone marrow transplantation procedures are needed mainly in developing countries., Methods: Between May 1993 and February 1999 in a private-practice setting, we performed 29 autotransplants in 28 patients using non-cryopreserved and unmanipulated peripheral blood stem cells mobilized from the bone marrow to the peripheral blood by means of hematopoietic growth factors. The autografting procedure was performed entirely on an outpatient basis in 19 cases (65%). The median age of the patients was 30 years, with a range of 9-67. There were 15 patients with acute leukemia (9 with acute myelogenous leukemia), 3 with chronic myelogenous leukemia, 2 with multiple myeloma, 3 with Hodgkin's disease, 2 with non-Hodgkin's lymphoma, and 4 with metastatic breast carcinoma., Results: The median time to achieve > 0.5 x 10(9)/L granulocytes was 14 days (range 7-42), whereas the median time to achieve > 20 x 10(9)/L platelets was 20 days (range 5-49). The 64-month post-transplant survival was 38%, whereas the median post-transplant survival was 18 months. The transplant-related mortality was 3.4%. The approximate cost of this simplified procedure was 10.8% for in-hospital procedures and for outpatient autografts, substantially lower than figures reported from the U.S. for autotransplants., Conclusions: This simplified method for autografting patients, avoiding in-hospital stays, purging procedures and cryopreservation of the cells is feasible and results in a substantial decrease of the cost of autologous hematopoietic stem cell transplantation methods.

In an effort to identify alleles associated with an increased risk of venous thrombosis in patients with primary antiphospholipid syndrome, we studied the G20210A polymorphism (the G-->A mutation at nucleotide position 20210) in the 3'-untranslated region of the prothrombin gene in a group of 14 patients with primary antiphospholipid syndrome. We did not find any patient with the mutated gene. Since the prothrombin mutation is more prevalent in white populations, this finding may be related with the genetic composition of the Mexican mestizos, in whom the white component is low. The polymorphism of the prothrombin gene in Mexican mestizo patients with antiphospholipid syndrome does not seem to be related to the thrombophilia observed in these patients.

Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults living in Western countries, and accounts for approximately 30% of adult leukemias. In a 15-year period in a single institution, we identified 19 patients with CLL in a group of 211 adults with leukemia (9% of adult leukemias). Of these 19 CLL patients, 8 had a Caucasian phenotype, 4 were born outside the country, and only 11 were Mexican mestizos. On the other hand, in a multicenter experience involving 1968 Mexican adults with leukemia, CLL represented 6.6% of the cases, a figure significantly lower than that reported in Caucasians (P < 0.01). CLL is the least frequent type of leukemia in Mexican mestizos, and this low prevalence may stem from the genetic origin of this racial group. The data also suggest a genetic predisposition of Caucasians to suffer from this disease.

The peripheral blood cells of ten patients with biopsy-proven aplastic anemia were studied by means of flow-cytometry in order to assess the expression of two phosphatidylinositol-anchored surface proteins: CD55/DAF (decay accelerating factor) and CD59/MIRL (membrane inhibitor of reactive lysis). An abnormal expression was found in five of these ten patients, whereas the "traditional" tests for paroxysmal nocturnal hemoglobinuria (PNH) were positive only on two of these five individuals. Five of the aplastic patients were treated with anti-thymocyte globulin and cyclosporin-A and three entered a complete remission; of the latter, one had CD55/CD59 deficiencies whereas two did not. Along the study period one patient with a hemolytic pattern of PNH was identified. It is concluded that CD55 and/or CD59 abnormalities are frequent in Mexican mestizo patients with aplastic anemia, that the aplastic presentation of PNH is more frequent in Mexico than the hemolytic presentation, that the flow-cytometric identification of CPI-anchored proteins is more sensitive than the "traditional" PNH tests, and that some patients with PNH-aplasia may respond to intensive immunosuppressive treatment. The flow-cytometric identification of GPI-anchored cell surface proteins should replace the "traditional" tests in the identification of patients with PNH.

To investigate whether metoclopramide-induced prolactin release is impaired in HIV-infected men, we studied 10 clinically healthy HIV-negative adult men (group 1) and 10 consecutive HIV-positive adult men (group 2) with anti-HIV antibodies confirmed by Western blot analysis and a CD4 cell count from 13 to 570x10(6)/L. After a 10- to 12-hour overnight fast, three basal blood samples were obtained at 15-minute intervals (-30, -15, and 0 minutes) and thereafter at 15, 30, 60, 90, 120, 180, and 240 minutes after a 10-mg intravenous bolus of metoclopramide. Duplicate serum prolactin concentrations were measured in each sample with commercially available radioimmunoassay kits. No significant differences between groups were observed in basal prolactin levels. Group 2 had lower serum prolactin concentrations than group 1 throughout the test (P< or =.002). The area under the prolactin curve (mean +/- SD) was also lower in group 2 than in group 1 (7156+/-1433 ng/mL/240 min vs. 12430+/-2454 ng/mL/240 min, P<.0001), and the area under the prolactin curve had a significant correlation with the CD4 cell counts (r = 0.7912, P<.001). These findings suggest that the hypothalamic dopaminergic tone, although present, was clearly diminished in these HIV-positive men regardless of their clinical stage.

A group of 102 Mexican Mestizo patients with appropriate clinical features suggestive of primary thrombophilia was prospectively studied. Thirty-nine percent of them had activated protein C resistance, but only four patients displayed the factor V Leiden mutation. Five percent of the individuals were found to be protein C deficient, whereas 2% had protein S deficiency. No cases of abnormalities in antithrombin III, plasminogen, tissue-type plasminogen activator or plasminogen activator inhibitor were found. The low prevalence of the activated protein C resistance genotype, probably stemming from the genetic admixture of the Mexican Mestizo group is noteworthy.

The postoperative complications observed in a group of 27 patients with hematological diseases that underwent splenectomy are reported: 21 patients had a non-malignant hematological condition, whereas the rest had a hematological malignancy. Seven complications presented in 6 patients (two wound infections, two severe post-operative hemorrhages, one incisional hernia, one sepsis by capsulated bacteria and one fatal hemophagocytic syndrome). The overall complication rate was 27%, whereas the fatal complication rate was 3%. The complication rate in patients with malignant diseases was 83%, whereas that in benign conditions was 9%. The size of the spleen was related with the complication rate (median weight of patients with complications was 990 g versus 132 g in those without complications; p < 0.01). The two patients that underwent splenectomy before age six months had complications, in one case related to parental negligence. In splenectomies performed for hematological disease the benefits must be balanced carefully against the risks.

We have prospectively performed peripheral blood stem cell autotransplants in six patients with hematological malignancies on an entirely outpatient basis. Patients were conditioned with high-dose melphalan and received a median of 4.2 x 10(8)/kg non-cryopreserved, non-purged mononuclear cells, containing a median of 3.9 x 10(6)/kg CD34 + cells. The median time to achieve > 500 granulocytes/microl was 21 days, with a range of 16 to 40, whereas the median time to achieve > 20,000 platelets/microl was 38 days, with a range of 21 to 48. Only three patients were transfused with platelets whereas packed red blood cells were transfused in two. All patients survived 60 days after the autograft and three are alive at 450, 690, and 1,950 days after the autotransplant. One patient was given an allogeneic bone marrow transplant when relapsing after the autotransplant. One patient had to be admitted to the hospital on day +10 because of fever. A median of 6,500.00 USD per patient was calculated as the total cost of each outpatient autotransplant. Since outpatient autologous transplants with non-frozen PBSC are feasible, restrictions to PBSC autotransplant programs may be overcome and costs may be diminished.

Six consecutive patients with promyelocytic leukaemia displaying the PML/RAR-alpha fusion messenger ribonucleic acid (mRNA)--the molecular marker of the disease--were prospectively treated with all-trans retinoic acid: Haematological complete remission was achieved in all of them. However, in three of them the PML/RAR-alpha mRNA persisted. Subsequent treatment with ablative chemotherapy rendered the molecular remission in all cases. Two of the patients that did not achieve the molecular remission with ATRA were autografted with peripheral blood stem cells after clearing the PML/RAR-alpha fusion mRNA. One patient with tretinoin-induced molecular remission relapsed two years after diagnosis and died; the remaining five survive in complete haematological and molecular remission for periods ranging from 405 to 1695 days. Additional studies are needed to clarify the significance of the molecular follow-up of patients with PML.

A patient with a stage IV high-grade non-Hodgkin's lymphoma who developed a fatal hemophagocytic syndrome is presented: When the patient had achieved complete remission and receiving fludarabine and chlorambucil/prednisone, she developed miliary tuberculosis, the CD4+ T-cell count then being 50/microL; the hemophagocytic syndrome ensuing at this point was fatal. Speculations about the predisposing factors that could have led to this complication are discussed focusing on the severe cellular immunosuppression which developed probably related to the use of fludafabine: it could be useful in the future to use anti-tuberculous prophylaxis in selected patients treated with this purine nucleoside analog.

The case of a 32-year-old female patient with a primary form of the antiphospholipid syndrome is presented. The initial symptom was a pathological form of hiccough, refractory to conventional therapy that was followed, weeks later, by a full-blown picture of transverse myelitis. Despite the fact that transverse myelitis has been described as associated with the presence of antiphospholipid antibodies, we could not find the description of refractory hiccough as the initial manifestation of the antiphospholipid syndrome. The administration of steroids, heparin and plasmapheresis resulted in resolution of the neurological symptoms.

The majority of children on earth are to be found in the developing world, many of them malnourished members of impoverished families. Thus, the effects of socio-economic status (SES) on the therapeutic response of children with cancer are obviously relevant. The outcome of treatment in patients with the commonest form of cancer in childhood (acute lymphoblastic leukemia, ALL) is clearly related to their SES. Studies conducted mainly in developing countries have shown malnutrition to be an important prognostic factor in such children. However, other socio-economic conditions could affect the outcome of therapy in patients with ALL: access to communications, transportation, laboratory studies and therapy. Even in children with an "adequate" SES, malnutrition is still an adverse prognostic factor. Nutritional supplementation appears to be a valuable addition to chemotherapy in undernourished children with ALL. The choice of treatment for these children should accommodate the cultural, economic and nutritional status of the patients and their families. Protocols must be created for testing methods of nutritional intervention and their influence on pharmacology, drug tolerance and survival in ALL. The influences of poverty and illiteracy on compliance with treatment, especially oral medication, need to be evaluated. Such investigations are essential to improve results of treatment of socio-economically disadvantaged children suffering from ALL and other forms of cancer.

Because radiotherapy (RT) equipment technology in some developing countries is outdated, its side effects are more frequent and severe and its efficacy suboptimal, whereas chemotherapy (CT) meeting international standards is generally more consistent. With this in mind, we treated 29 patients with stages I and II Hodgkin's disease with the MOPP or the MOPP/ABV hybrid schedule without prior staging laparotomy. The complete remission rate was 96%: five patients relapsed and of these, two died and three were rescued with CT, in one case followed by an autologous stem cell autograft. The median follow-up is 54 months (range 9 to 126), the overall survival of the group 88% at 126 months, and the relapse-free survival 72% at 110 months. Conventional CT alone has been shown to be useful in achieving acceptable long-term results. This observation could be important in circumstances where RT is unavailable or of suboptimal quality.

In the course of 120 months we have prospectively treated 45 patients with acute leukemia aged 11 to 21 years: 33 with acute lymphoblastic leukemia (ALL) and 12 with acute myelogenous leukemia (AML). Patients with ALL were treated with St. Jude's protocol XI: there were five early deaths and complete remission (CR) was achieved in 76% (89% of those completing one month of treatment); median survival (SV) was 29 months and the 120-month SV was 35%. AML patients with promyelocytic leukemia were induced to remission using all-trans-retinoic acid, whereas those with other types of AML were given the classic 7 + 3 scheme: the CR rate was 85%, median survival has not been reached and the 33 month survival was 72%. Four patients with AML were given peripheral blood stem cell autografts as part of the post-remission therapy. Our data in ALL and AML appeared to be intermediate to those in children and adults.

Two patients with hypergranular acute lymphoblastic leukemia are presented: they represent 1.4% of patients with acute lymphoblastic leukemia studied and treated in a single institution in the past 12 years. This frequency is substantially lower than that reported in Caucasian populations. The blast cells of the patients disclosed an early-B phenotype, displaying CD45, CD10 and CD19 antigens. The cytoplasmic granules were positive for the PAS reaction. Both patients died early after starting treatment; a poor prognosis has been recorded previously for patients with this type of malignancy.