Months Of Remission Research Articles

Computed tomographic and histopathological studies of pontine glioma.

Correlative study of computed tomography (CT) and pathologic findings was performed in eight cases of pontine glioma. All patients except one had chemotherapy and radiotherapy, with no surgical intervention. On initial CT scans, all patients had hypodense lesions in part or the whole of the pons, and there was evidence of mass effect. Four of eight cases showed contrast enhancement. After chemotherapy and radiotherapy, swelling of the pons and the width of the hypodense areas decreased. The hypodense areas sometimes became isodense in correlation with clinical amelioration. After several months of remission in responding cases, ring-enhanced lesions reappeared at the primary site, together with recurrent neurological signs. Pathological study postmortem was focused on the histological counterparts of the CT findings of central and perifocal hypodense areas and contrast enhancement. In six of seven treated cases, the central hypodense area surrounded by ring enhancement was shown to be coagulation necrosis. Higher cellularity and hypervascularity with glomeruluslike structures of small vessels were generally observed in enhanced areas. The areas diffusely infiltrated by tumor cells, but not enhanced in CT scans, had few abnormal vessels. Tumor cells were seen not only in hypodense areas around the enhanced portion but also in areas far beyond the enhanced portion. Exophytic expansion of tumor was observed in two cases on postmortem examination. One of these was detected by CT scans before death.

Heat production rate in polymorphonuclear granulocytes from patients with acute myelogenous leukaemia and healthy individuals.

Heat production rate in polymorphonuclear granulocytes (PMN) from 18 AML patients and 21 healthy individuals was measured using microcalorimetry. An increased PMN heat production rate was found in most AML patients at diagnosis and during the first 6 months of remission. In 7/7 patients showing values above the normal mean level the heat production rate decreased during sequential analysis. The increased PMN heat production rate is serum dependent and leukaemic sera induced increased calorimetric values also in PMN from healthy donors. This effect was not due to heat labile complement factors.

Comparison of Central Nervous System Prophylaxis With Cranial Radiation and Intrathecal Methotrexate Versus Intrathecal Methotrexate Alone in Acute Lymphoblastic Leukemia

AbstractIn 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 >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 < 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 × 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.

Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

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.

Circulating immune complexes and the prognosis of acute myeloid leukemia.

We studied the relation between the clinical course and the presence of circulating immune complexes at diagnosis and/or during complete remission in 186 patients with acute myeloid leukemia. Patients with immune complexes at diagnosis had significantly fewer complete remissions (32 vs. 94 per cent), remissions of shorter duration (median, 4.3 vs. 15.0 months), and shorter survival times (median, 1.8 vs. 22.3 months) than patients without such complexes (all comparisons, P less than 0.01). All patients with immune complexes during the first two months of remission remained in remission for less than six months, whereas only 11 per cent of patients without complexes within this period had such early relapse. Of 23 patients who relapsed after long remissions, 18 (78 per cent) had immune complexes that preceded hematologic evidence of relapse by three weeks to six months (median, 3.7 months). These findings suggest that circulating immune complexes may reflect an important aspect of the pathophysiology of acute myeloid leukemia, and that measurement of these complexes can provide useful prognostic information at diagnosis and during remission.

Implications of terminal deoxynucleotidyl transferase activity in various forms of childhood leukemia (author's transl)

Terminal deoxynucleotidyl transferase (TdT) was examined in mononuclear peripheral blood cells (pB) and bone marrow (BM) specimens of 63 children with acute leukemia (AL). The enzyme activity in normal specimens (pB, BM) was below 0.2 U/10(8) cells; whereas, 49 of the 52 children with acute lymphoblastic leukemia (ALL) at diagnosis showed an activity in the range 1.2--60 U/10(8) cells. 2 of the remaining 3, devoid of TdT activity, were found to be B-cell leukemia. Patients with acute non-lymphoblastic leukemia (ANLL) were generally TdT-negative. Elevated level of TdT activity was detected in only one of 11 children with ANLL. In one patient with acute leukemia two distinct populations of cells with lymphoblastic (87%) and myeloblastic characteristics were evident. The clinical course and cell marker studies were consistent with the interpretation of a defect at the level of the common stem cell giving rise to a TdT-positive lymphoblastic cell population at diagnosis and, following the initial ALL-therapy (4 weeks), a predominant TdT-negative myeloblastic population. TdT as a marker for the modulation of chemotherapy was examined in the remission phase of the disease. Of the nine patients in the first 3 months of remission, one was found to have elevated level of TdT activity (2.5 U/10(8) cells). These data define the usefulness of TdT in the classification of acute leukemia.

Acute Myeloid Leukaemia with the Philadelphia Chromosome

A case report of serial chromosome studies on a 26-year-old male with acute myeloid leukaemia (AML) is presented. The classic Philadelphia chromosome (Ph1) translocation, t (9;22) was found in 77% of the metaphases at diagnosis and in 100% in relapse; during a 3-month remission period the cytogenetic picture was normal or the Ph1 was present in a minor cell population only. The clinical and morphologic features of this case indicated that it was really a case of AML and less likely chronic myeloid leukaemia (CML) presenting in blast crisis. It is suggested that the oncogen producing the 9;22-translocation and CML may also induce AML in rare instances.

Period of freedom from relapse as an indication of cure in minimal change nephrotic syndrome in adults.

17 adult-onset nephrotic patients with minimal-change glomerular lesions experienced 39 relapses in all. The relationship between the remission period t (expressed in months) preceding each relapse and the rate of relapse (relapse rate) F (t) was proven to correspond closely to Weibull's distribution function as follows (chi 2 = 1.72, 0.5 less than p less than 0.75): In In (formula - see text) From the equation, the time when 99% of relapsing patients have relapsed is 39.3 months. This means that adult-relapsing nephrotic patients with minimal-change lesions will experience a relapse within 39.3 months of remission. They should be free from relapse and considered cured with a 99% reliability when remission has continued longer than 39.3 months, i.e. beyond the 'period of freedom from relapse'.

Pancreatic islet transplantation in the rat.

Twenty to thirty-five neonatal rat pancreases (2.5 to 4.5 days postpartum) were minced, dissociated in a collagenasetrypsin-EDTA solution, washed, centrifuged, resuspended in Tyrode's solution, and transplanted intraperitoneally to an alloxan-diabetic recipient. All of eight highly inbred moderate-diabetic rats (mean pretransplant blood sugar level and daily urine glucose excretion = 340 mg./100 ml. and 6.0 gm., respectively), showed a reversal of the diabetes within several days following isotransplantation (blood sugar and daily urine glucose excretion levels dropped to less than 150 mg./100 ml. and 0.1 gm., respectively). Two of seven highly inbred severe-diabetic rats (mean pretransplant blood sugar level and daily urine glucose excretion = 440 mg./100 ml. and 8.0 gm., respectively), recovered from their diabetes about two weeks following isotransplantation. In these highly inbred recipients which recovered from their diabetes, normoglycemia has persisted for more than five months. Control animals receiving liver transplants showed no significant changes in their diabetes. Exploration of the peritoneal cavity, after two months of remission, demonstrated isolated implants in association with the liver, spleen, pancreas, abdominal wall, etc. Yascularized grafts consisted primarily of cords of heavily granulated (aldehyde fuchsin positive) beta cells. Acinar cells were not identified. By contrast, the recipient pancreas showed few identifiable beta cells (characteristic of alloxan diabetes), but these were heavily granulated, presumably because of the controlled diabetic state. In some grafts, removed several days following implantation, mitotic figures were seen in cells containing aldehyde fuchsin positve granules. Similar homotransplants were carried out in thirty-seven partially inbred moderate-diabetic recipients; 46 per cent showed a transitory recovery from their diabetes lasting three to thirteen days. However, the pretransplant diabetes was re-established in one to three weeks and this was attributed to the rejection of the transplant. These studies indicate that dissociated neonatal pancreas forms functional islet implants capable of reversing diabetes in alloxanized rats.

Effect of norethynodrel on endometriosis

The authors selected norethynodrel for conservative therapy beginning in 1958 because of the hormones lack of androgenic effect inhibition of ovulation and estrogenic effect. Minimal duration of therapy was planned to be 6 months. By 1960 there were 123 patients diagnosed at Walter Reed General Hospital as having endometriosis and suitable for this treatment. Ill patients were diagnosed by culdoscopic examination and results were confirmed by the same method. 11 were diagnosed by laparotomy and 1 by colpotomy. Ages ranged from 20 to 46 years with an average of 32.8. Most frequent symptoms were dysmenorrhea dyspareunia infertility menorrhagia metrorrhagia and pelvic pain. Treatment started with 2.5 mg daily and was increased rapidly to 30 mg daily. When breakthrough bleeding occurred further increases were made in 10 mg increments up to 100 mg daily. The average dose was 49.2 mg daily. Adjacent organs and tissues particularly the ovaries were often involved. For the entire group 63 patients (79.7%) showed complete regression of endometriosis 8 showed improvement 10 were not improved. Regression rate was the same regardless of the patients age or the severity of the disease. Of side-effects irritability and nervous tension abdominal cramping vaginal discharge and leg cramps were most common. All patients gained weight. 5 required psychiatric treatment. Cervical and vaginal smears obtained before and after therapy revealed no evidence of cellular atypism. Significant uterine enlargement was noted. Estrogen effect and high progesterone effect were noted during therapy but reverted to normal when treatment ceased. Incidence of trichomonads and Candida was less than 15%. Histological examination of tissue removed by curettage after therapy showed a marked stromal decidual reaction with absence or atrophy of glandular elements. 9 patients required major surgery after 1-12 months of treatment. Of 28 patients followed up for an average of 10.9 months recurrences developed in 5 after 7.2 months of remission; in 1 of these 6 additional months of therapy produced remission. Normal ovulation returned but was delayed. 4 patients from the group of 38 who had been infertile for 3-9 years became pregnant.