Biomedical subjects
Publications and source records attributed to G Garay.
The authors present a case of monocytic aleukemic leukemia cutis in which skin symptoms were the sole manifestation of the leukemia during the first year and a half of the disease. Diagnostic difficulties, the importance of immunohistochemical markers, and the prognosis and therapy of aleukemic leukemia cutis are discussed.
The authors present a 39 year old female patient with acute monoblastic leukemia, at whom during a year and a half the disease was manifested only with specific skin symptoms (leukemia cutis). Diagnostic difficulties, importance of immunhistochemic markers, as well as diagnostic, prognostic and therapeutic role of aleukemic leukemia cutis are discussed.
Urinary excretion of aluminium after a successful transplant can reverse pre-transplant aluminium intoxication. We have evaluated the time course of urinary aluminium excretion and its correlation with several parameters of renal function and mineral metabolism in 49 patients (33 men and 16 women) with a wide range of pre-transplant serum aluminium concentrations, performing sequential determinations at pre-transplant time and at 7, 30, 60, and 90 post-transplant days. Mean serum aluminium at pre-transplant was 54.5+/-46.8 microg/l decreasing progressively to 28.7+/-24.4 microg/l at 90 days (P<0.0002), paralleling the decrease in serum creatinine. Urinary aluminium decreased from 63.0+/-77.9 to 52.4+/-55.9 microg/l at 90 days (P<0.0001). The maximum urinary aluminium/creatinine was 1.8+/-2.7 at 7 days and was associated with the greatest fractional excretion of sodium (4.7+/-5.1%), and the lowest tubular reabsorption of phosphate (55.7+/-25.1%). The fractional excretion of aluminium was also greatest at day 7 (1.1+/-0.9%) when serum creatinine was still elevated (3.6+/-2.3 mg/dl). At each period of time after transplantation fractional excretion of aluminium was similar in all patients despite disparate serum aluminium concentrations. Fractional excretion of aluminium was highest in those patients who developed post-Tx acute tubular necrosis (0.7+/-0.5 vs 1.5+/-1.0%, P=0.008). We found a direct positive correlation (r=0.43; P<0.002) between urinary aluminium and urinary phosphate. Basal levels and sequential changes in serum PTH, calcium, and phosphate did not correlated with fractional excretion of aluminium. These findings suggest: (i) urinary aluminium remains elevated during prolonged periods after transplant and is probably a marker of pre-transplant tissue aluminium accumulation; (ii) post-transplant fractional excretion of aluminium seems to correlated positively with other evidences of renal tubular dysfunction. Early post-transplant tubular malfunction could significantly enhance urinary aluminium elimination.
In this study, 54 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated in a phase II, multicentric trial with ifosfamide-mesna 1500 mg/m2 IV days 1-3, idarubicin 12 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 (MIZE). Overall response was 72%; complete response (CR) and partial response (PR) were 46% and 26% respectively. In Stage I-II pts CR was 59% and in Stage III-IV pts CR was 40.5%. Patients who relapsed from an initial CR had a 64% CR rate when treated with MIZE, in contrast to refractory disease's patients who only had 19% CR (p = 0.004). The group of pts that had an objective response (CR + PR) to front line therapy had a 2 year survival rate of 55% compared with none for refractory disease (p = 0.029) after salvage therapy. Median survival for the entire group was 17.5 months. Better survival was seen in pts who were asymptomatic with low levels of LDH, previous CR, non high-grade histology, and limited disease stage at relapse. Toxicity was mainly hematologic: 91.5% had neutropenia, (56.5% grade III-IV), and 9.5% died from infectious complications. Other clinical toxicities including cardiac toxicity were negligible. MIZE chemotherapy was effective in patients with relapsed and refractory lymphoma and showed limited clinical and cardiac toxicity. Myelosupression was the most frequent single toxicity.
Aluminium intoxication exerts profound effects on secondary hyperparathyroidism in chronic renal failure and could influence the evolution of post-transplant parathyroid function. We have evaluated 44 patients after successful renal transplantation, sequentially from day 0 up to day 90 from the beginning of graft function, determining serum and urinary aluminium, PTH (intact molecule) and several other parameters of mineral metabolism. Patients were grouped according to their basal serum aluminium: Group LA (n = 25) had serum aluminium less than 40 micrograms/l (mean 21 +/- 10 micrograms/l), and Group HA (n = 19) had serum aluminium greater than 40 micrograms/l (mean 100 +/- 43 micrograms/l). This latter group also had greater urinary aluminium excretion during the study period. Evolution of renal function was similar in both groups. Group LA had increased pre-transplant iPTH (353 +/- 416 pg/ml vs 175 +/- 94, P = 0.05). Seven days after regaining renal function both groups showed a marked decrease in iPTH and then a continued decline up to day 90 with mean serum values of the hormone showing no further differences between groups. The incidence of hypercalcaemia was similar in both groups but no patients in Group HA developed hypercalcaemia at post-transplant day 7 while 12% in Group LA did so. Urinary phosphate excretion and the incidence of post-transplant hypophosphataemia were similar in both groups. These findings suggest: (a) patients with more aluminium intoxication have lower values of pre-transplant iPTH and they correct parathyroid function in a different way than non-intoxicated patients in early post-transplant days; (b) they have lower and later incidence of hypercalcaemia.
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Adriamycin (ADM) is an effective antineoplastic drug. However, the amount of ADM that can be administered must be limited because of the risk of developing a severe dose-dependent cardiomyopathy. 4'Epi-adriamycin (4'ADM) is a new anthracycline analog with similar antineoplastic properties as ADM, but with perhaps less cardiac toxicity. To determine myocardial performance after a chronic treatment with 4'ADM, we studied 17 patients (mean age 36.6 years) suffering from lymphomas by means of 24-hour ambulatory ECG, x-ray, M-mode echocardiogram, and rest-exercise gated radionuclide ventriculography (RNV), performed prior to and 2 months after the end of the treatment. Pretreatment and post-treatment shortening fractions, basal pretreatment and post-treatment ejection fractions, and postexercise pretreatment and post-treatment ejection fractions, were tested for correlation with individual 4'ADM doses and pretreatment with ADM. No association was noted among them, showing the lack of correlation between doses and impairment of ventricular performance. 4'ADM doses ranged from 400 to 1100, x 748 +/- 174 mg/m2; all noninvasive studies including RNV were normal. No correlation was found between 4'ADM doses and RNV (Pearson's correlation coefficient, p = ns). No deterioration of ventricular performance could be demonstrated. Conversely, the basal pretreatment ejection fraction changed from 56.17 +/- 7.6% to 61.52 +/- 8.3% in post-treatment (p less than 0.0001). Surprisingly, the post-exercise pretreatment ejection fraction also increased from 55.47 +/- 7.7% to 63.35 +/- 10% in post-treatment (p less than 0.03). The shortening fraction changed from 35.47 +/- 4.8% to 36.47 +/- 4.2% after 4'ADM treatment (ns). No impairment of cardiac function could be shown in patients previously treated with ADM or radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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In a randomized study with 234 previously untreated patients with multiple myeloma, 129 were treated with melphalan (8 mg/m2 perorally for four days) and prednisone (40 mg/m2 perorally for seven days, both every four weeks) and 105 with melphalan and prednisone at the same doses plus cyclophosphamide (600 mg/m2 intravenously every four weeks), MeCCNU (100 mg/m2 PO every eight weeks), and vincristine (MPCCV, 0.6 mg/m2 IV every four weeks). A total of 49 (38%) of the 129 patients treated with melphalan and prednisone (MP) and 48 (46%) of the 105 patients treated with MPCCV showed good response (GR) (P not significant); the overall response rates were 58% and 70%, respectively. Thirty-seven percent of the MP group and 39% of the MPCCV group remain alive at 48 months from first treatment (P not significant). The estimated 48-month survival from first treatment, according to different prognostic factors at diagnosis, in both groups was as follows: stage 1,56%; stage II, 46%, and stage III, 23% (I and II v III P less than .001). Survival at 48 months according to response was GR, 68%; partial response (PR), 33%; and null, 16% (GR v null, P less than .0005; GR v PR, P less than .0005). Survival according to renal function was 43% for a creatinine level less than 2 mg/100 mL and 27% for a creatine level greater than or equal to 2 mg/100 mL (P less than .0005). No significant difference has been found between the two treatment schedules in terms of response rate and survival time, in any stage of disease.
From January 1976 to December 1978, 347 children less than or equal to 15 years of age were entered in a collaborative controlled trial which included: induction (vincristine-daunorubicin-prednisone); intensification (cytarabine-cyclophosphamide); CNS prevention (intrathecal methotrexate-dexamethasone, three doses during induction and three weekly doses during the first month of maintenance, followed by one dose every 3 months for 48 months); and maintenance (6-mercaptopurine daily and methotrexate twice weekly with reinforcement pulse doses of either 1.5 mg/m2 X 1 of vincristine plus 40 mg/m2/day X 7 of prednisone [Arm A] or vincristine-prednisone alternating with 50 mg/m2 of cytarabine sc every 12 hours X 10 plus 600 mg/m2 X 1 of cyclophosphamide [Arm B]). Pulses were performed in both arms at 1, 2, 3, 4, and 6 months and every 3 months thereafter. Randomization was stratified according to age and initial wbc count. A total of 89% (310/347) of patients achieved complete remission. Duration of continuous complete remission was evaluated according to prognostic factor groups. At 5 years, 34.5% of patients with good prognosis, 24.8% with intermediate prognosis, and 12.8% with poor prognosis are in continuous complete remission. There is statistical difference between good versus poor prognosis (P less than 0.0005) and intermediate versus poor prognosis (P less than 0.025). Moreover, 5-year survival is 50.9%, 35.2%, and 18.2% in the good-, intermediate-, and poor-prognosis groups, respectively. Duration of continuous complete remission up to the first event (ie, bone marrow, CNS, or other extramedullary relapse, or death in complete remission), according to prognostic groups, did not differ in relation to reinforcement pulses (Arm A or B). We conclude that there was no benefit in alternating pulses of vincristine-prednisone with cyclophosphamide-cytarabine as used in this study.
Patients with resistant or recurrent acute lymphoblastic leukemia were treated with vindesine 3 mg/m2/IV weekly X 4, daunomycin 25 mg/m2/IV weekly X 4, and prednisone 40 mg/m2/PO daily X 28. Seventeen (44%) of 38 evaluable patients achieved complete remission. Fifty-one percent of 31 patients in first relapse achieved complete remission, while only one of five in second or third relapse and neither of two resistant to first induction achieved complete remission. The major toxicity was hematologic. The median duration of complete remission was only 6 weeks and median survival from start of the study, 3 months, with 22% patients remaining alive at 10 months. We conclude that the vindesine, prednisone, and daunomycin combination is no more effective than vincristine, prednisone, and daunomycin in achieving remission of relapsed acute lymphoblastic leukemia patients, and is more toxic than the latter regimen.
Patients with recurrent acute lymphoblastic leukemia were treated with daunorubicin (40 mg/m2/week X 4), vincristine (1.5 mg/m2/week X 4), and prednisone (40 mg/m2/day x 28). All of the patients had been treated with the same combination during the first induction treatment. Of 266 patients (221 children and 45 adults) treated in first relapse, 141 (53%) achieved complete remission (CR; 55% of the children and 44% of the adults). Of 61 patients who were re-treated with the same combination after the second relapse, 14 (23%) achieved CR. The difference between second and third CR was statistically significant (P less than 0.0005). The median durations of second and third CR were 8 and 6 weeks, respectively. No significant difference was observed when the duration of CR was compared with the initial wbc count, age at diagnosis, or duration of first CR.
In acute lymphoblastic leukemia (ALL), central nervous system (CNS) prophylaxis with cranial irradiation plus 5 doses of intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity started to be recognized as CT scan abnormalities and neuropsychologic alterations, mainly in children. Two questions were analyzed in the present report: (1) Will further doses of i.t. methotrexate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse in patients treated early in remission with cranium irradiation plus i.t. MTX-DMT even more? (2) Is i.t. MTX-DMT given during induction and maintenance equally as effective as cranium irradiation plus i.t. MTX-DMT? A randomized study was designed to answer the first question. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count less than 50,000 was 11% (15 of 135 patients) and was 11% (17 of 150) in the untreated group. In patients with a WBC count greater than 50,000, it was 16% (6/37) in the treated group and 19% (6/31) in the control group. No difference was observed according to treatment in both prognostic groups. Patients in this study were retrospectively compared with a consecutive protocol in which patients received 3 doses of i.t. MTX-DMT alone during induction plus 3 doses weekly during the first month of remission and every 3 mo thereafter. The incidence of primary CNS leukemia at 60 mo in patients with a WBC count less than 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. This difference was not significant. However, the relapse-free survival at 60 mo was 26% and 41%, respectively, (p less than 0.0005). The incidence of primary CNS relapse in patients with a WBC count more than 50,000 at 48 mo was 28% in the irradiated group and 42% in the nonirradiated group. The difference was not significant. The duration of complete remission was similar, remaining at 15% and 16% of patients disease-free at 48 mo, respectively. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) the use of i.t. MTX-DMT alone compares similarly with cranial irradiation plus i.t. MTX-DMT in the incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count less than 50,000 were significantly longer in those without cranial irradiation.
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Patients with acute lymphoblastic leukemia (ALL) who were in two consecutive protocols and in complete remission (CR) with maintenance therapy, were randomized to receive or not receive levamisole. A total of 15 of 55 low-risk patients of protocol 10-LLA-72 with levamisole had relapses, compared with 25 of 54 not receiving levamisole; 67 and 49%, respectively, remain in CR at 48 months (P less than 0.025). In protocol 1-LLA-76, 14 of 91 low-risk patients on levamisole and 25 of 93 patients receiving levamisole had relapses; 78 and 61%, respectively, remain in CR at 36 months (P less than 0.05). Seventeen of 39 high-risk patients (children with a leukocyte count higher than 50,000 and adults) receiving levamisole had relapses compared with 37 of 61 not on levamisole. The DNCB skin test showed at 18 and 24 months a 74 and 85% positivity in the levamisole groups vs. a 38 and 35% positivity in the control group (P less than 0.025). We conclude that levamisole prolongs the duration of CR and survival in low-risk patients with ALL.
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