Biomedical subjects

A Cork

Publications and source records attributed to A Cork.

At least 73 records · Page 4Linked to original sources

PubMed1988

Phenotypic and molecular heterogeneity in Philadelphia chromosome-positive acute leukemia.

Philadelphia chromosome-positive (Ph1) acute leukemia is a heterogeneous subset of acute leukemia with a poor prognosis. We studied five patients to determine the potential for phenotypic and molecular heterogeneity. Cellular characterization studies included light myeloperoxidase (L-MPO), terminal deoxynucleotidyl transferase (TdT), ultrastructural MPO (U-MPO), and immunophenotyping by flow cytometry using T11, T3, T4, T8, Leu 1, B1, Leu 12, HLA-DR (la), CALLA (J5), OKM1, My4, My7, My8, My9, and My10. DNA was analyzed for rearrangements of the breakpoint cluster region (bcr), immunoglobulin heavy chain, joining region (JH), immunoglobulin kappa light chain constant region (C kappa), and T cell receptor (TcR beta). RNA dot blots were hybridized by using molecular probes for MPO and TdT. We found that four of five cases were acute mixed-lineage leukemia (AMLL). One patient had acute unclassifiable leukemia. Of the four patients classified as having AMLL, three showed myeloid and lymphoid features, with one patient showing myeloid, T cell, and B cell features. The last case showed T cell and B cell features only. In one patient MPO/RNA was positive in spite of insufficient L-MPO or U-MPO to diagnose acute myelogenous leukemia (AML), thereby suggesting significant MPO gene expression before the production of sufficient MPO protein to meet the French-American-British criteria for AML. Three of the five patients showed rearrangement of bcr (cases 1, 2, and 5). Studies of these five patients support the concepts of molecular and phenotypic heterogeneity in Ph1 acute leukemia, demonstrate a high incidence of AMLL in this subset of acute leukemia, and support the use of lineage-associated molecular probes to define lineage at an earlier stage than previously possible.

Acute Disease↗

PubMed1988

Cytogenetic features of Hodgkin's disease suggest possible origin from a lymphocyte.

Surface marker and gene rearrangement data have supported various hypotheses about the origin of the malignant cell in Hodgkin's disease. Cytogenetic data about this disorder, however, are very scanty. To determine if any chromosomal abnormalities that could add further information to this controversial point are present, we studied tumor samples from 49 patients. Abnormal metaphases were obtained in 18 cases. The most common breakpoints were in 11q23, 14q32, 6q11-21, and 8q22-24. These are common breakpoints in lymphoma and raise the possibility that the malignant cell in Hodgkin's disease may be derived from a lymphocyte. The 11q23 breakpoint is also seen in t(4;11) and t(9;11), which is typical of a type of childhood B-cell acute lymphoblastic leukemia characterized by the presence of aberrant myeloid and monocytic markers. Myeloid and monocytic markers are common in Reed-Sternberg cells.

Chromosome Aberrations↗

PubMed1987

Therapeutic modalities for central nervous system involvement by granulocytic sarcoma (chloroma) in children with acute nonlymphocytic leukemia.

Four cases of central nervous system involvement by granulocytic sarcoma (three intracranial and one paraspinal) in children with acute nonlymphocytic leukemia (FAB M1 or M2 subtype) are presented, and therapeutic modalities are discussed. All tumors were noted at initial presentation with diagnosis being made on clinical and radiological findings without biopsy. All patients had karyotypic abnormalities: three had translocation of chromosomes 8 and 21, and one had an unspecified hypodiploid clone. The three patients who developed intracranial tumors responded well to triple agent (cytosine arabinoside, hydrocortisone, and methotrexate) intrathecal chemotherapy and systemic chemotherapy, with or without local irradiation, as evidenced by rapid disappearance of the tumors. Two children are disease-free after 17 and 57 months. One patient with paraspinal tumor failed to achieve a systemic remission but had no evidence of granulocytic sarcoma at autopsy. Thus, the prognosis of CNS granulocytic sarcoma is not uniformly gloomy if treated aggressively by combined modalities. The value of surgical intervention in terms of primary management, however, is limited.

Acute Disease↗

PubMed1987

Chronic myelogenous leukemia in blast crisis. Analysis of 242 patients.

Two hundred forty-two patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis were reviewed to identify significant biologic and prognostic associations. Twenty percent of patients had lymphoid blast crisis. Clonal evolution was present in 60 percent of patients at blast crisis and involved most frequently the development of a double Philadelphia chromosome, trisomy 8, or isochromosome 17. The overall median survival from blast crisis was 18 weeks. Patient characteristics demonstrated to have significant association with short survival were: anemia; thrombocytopenia; myeloid or undifferentiated blast cell morphology; clonal evolution involving the presence of a double Philadelphia chromosome, trisomy 8, or isochromosome 17; and low marrow blast percentage. Of 195 patients who received therapy for blast crisis, complete remission was achieved in 44 (23 percent) patients, and 24 (13 percent) patients had a partial remission or hematologic improvement. Lower complete remission rates were associated with old age, thrombocytopenia, myeloid or undifferentiated blast cell morphology, clonal evolution--especially isochromosome 17 and trisomy 8--and long interval from diagnosis to onset of blast crisis. A multivariate analysis identified two characteristics to have independent prognostic importance for both survival and remission: platelet counts and blast cell morphology. In addition, clonal evolution had additive prognostic value for survival (double Philadelphia chromosome) and for response (isochromosome 17). The beneficial association of therapy with survival was demonstrated by the significantly longer median survival of patients treated since 1981 compared with those treated earlier, even after accounting for the pretreatment prognostic factors, and by the significant improvement in survival of patients achieving remission using the "landmark" analysis technique.

Blast Crisis↗

PubMed1987

Toward a clinically relevant cytogenetic classification of acute myelogenous leukemia.

Cytogenetic studies with Giemsa banding were performed on the bone marrow cells of 384 patients with acute myelogenous leukemia treated between 1975 and 1983. An abnormal karyotype was detected in 54% of patients, being present in 100% of metaphases (AA) in 31% and only a proportion of cells (AN) in 22%. Specific translocations or other abnormalities were noted in 22% of patients, the most common of which were t(8;21) (q22;q22) in 7%, t(15;17) (q22;q21) and inv (16) (p13q22) in 5.5%, t(9;22) (q34;q11) in 3% and abnormalities of 11q23 in 1.3%. Loss of the Y chromosome was noted in 21 patients, associated with t(8;21) in 11 patients and the sole abnormality in eight patients (45, X, -Y). Most (66%) of the other abnormalities involved addition of chromosome 8 or loss or deletion of 5 or 7 (+8, -5 or -7, 5q- or 7q- group). The remaining patients had miscellaneous abnormalities (MA). A marked assymetry was noted in the distribution of important clinical prognostic variables such as age, sex, history of an antecedent hematologic disorder and presence of Auer rods within the various cytogenetic categories. The specific translocation/abnormalities were more common in younger patients (p less than 0.01). Analysis of response, remission duration and survival demonstrated that inv 16 and t(8;21) were favorable prognostic categories; diploid, t(15;17) and 45,X,-Y had intermediate prognosis, and all other categories were unfavorable prognostic groups. The response rate and survival for diploid patients (NN) was superior to patients with abnormalities. No difference in response rate, CR duration or survival was noted between the AA and AN groups. A prognostic classification according to cytogenetic category based on clinical associations is proposed which will be tested prospectively in subsequent studies.

Adult↗

PubMed1987

Monosomy 21, partial duplication of chromosome 11, and structural abnormality of chromosome 1q21 in a case of lymphoma developing in a transplant recipient: characteristic abnormalities of secondary lymphoma?

Cytogenetic analysis by QFQ-banding of direct preparation of a testicular mass from a patient with secondary lymphoma revealed a modal chromosome number of 45,XY, including structural and numerical anomalies. The most consistent anomalies were the monosomy 21, duplication of the long arm of #11, and structural anomaly associated with chromosome #1 in band q21.

Adult↗

PubMed1987

DNA aneuploidy in adult acute leukemia.

Using flow cytometric techniques, we determined DNA ploidy levels in the bone marrow of 318 successive adult patients with newly diagnosed acute leukemia. Overall, 26% exhibited DNA stem line abnormalities, usually with a 10%-15% DNA excess, regardless of morphologic diagnosis. DNA aneuploidy was seen most frequently in patients with a hyperdiploid chromosome number and karyotype instability (50%), but was also present in a third of patients with chromosomal translocations and in 20% of patients with a normal diploid karyotype. Thus, among 73 patients with DNA aneuploidy, quantitatively concordant karyotype abnormalities were observed in almost 40% of patients; the discrepancy between DNA content and chromosome number in the remaining patients may reflect differences in the cell cycle position of target cells in G1/0 phase or mitosis, respectively. Cytogenetics affected treatment outcome in acute myelogenous leukemia (AML) with more favorable short- and long-term prognosis among patients with translocations compared with those with numeric abnormalities. The presence of an abnormal DNA stem line, among AML patients with translocations, identified a favorable subgroup with significantly longer remission duration and survival (25 and 26 months versus 18 and 13 months, respectively). In addition, the prognostic implications of DNA aneuploidy in AML were age-dependent, in that favorable effects among patients with translocations and unfavorable effects among those with numeric abnormalities or diploid karyotypes were most obvious in young and not in older patients (greater than or equal to 40 years). In adults with ALL, DNA aneuploidy was associated with shorter survival (15 versus 39 months in the diploid group), an observation that is distinctly at variance with recent findings in childhood ALL. Our results indicated that DNA flow cytometry was complementary to standard cytogenetics for the detection of genomic abnormalities; and DNA aneuploidy emerged, like in children but not in adults with ALL, as a new favorable prognostic feature in a subgroup of adults with AML, the biologic basis of which remains to be determined.

Adult↗

PubMed1987

Central nervous system complications of a newly recognized subtype of leukemia: AMML with a pericentric inversion of chromosome 16.

Ten patients with acute myelomonocytic leukemia (AMML) and inversion of chromosome 16 who had CNS involvement were identified at M.D. Anderson Hospital between January 1972 and December 1984. The nervous system signs and symptoms were evaluated in detail. CT scans, CSF cytologies, and treatment modalities were reviewed. Two patients underwent biopsies of lesions that proved to be granulocytic sarcomas. AMML with inversion 16 carries a much higher (33%) incidence of CNS involvement in the form of leptomeningeal metastasis and/or granulocytic sarcoma than all other acute nonlymphocytic leukemias (5%). The reason for this appears to be related to the chromosomal aberration and not to prolonged survival.

Adult↗

PubMed1987

Acute myelomonocytic leukemia associated with abnormalities of chromosome 16: a light and electron microscopic study.

We investigated the light and ultrastructural morphology of 37 patients with acute nonlymphocytic leukemia (ANLL) and inv(16)(p13q22) or del (16)(q22) with specific emphasis on the changes in the eosinophils (EOS). All but one of the 37 patients were classified as French-American-British M4 with eosinophilia (FAB M4-E) on the basis of the monocytoid nature of the leukemic cells and the presence of large EOS with interspersed basophilic-staining granules. A median of 92% of the blasts were peroxidase positive, and Auer rods were found in 71% of cases. Only 27% of the cases had sufficient alpha-naphthyl butyrate positivity to confirm the diagnosis of FAB M4, but electron microscopy demonstrated a sufficient monocytic component to support this classification in all cases examined. Electron microscopy also demonstrated nuclear blebs both in the blasts and notably, in the EOS of all cases examined (16 of 16). Nuclear blebs in EOS were found in only 1 of 13 cases of ANLL that showed eosinophilia but lacked abnormalities of chromosome 16. This case was also classified as FAB M4-E. The finding of nuclear blebs in EOS in FAB M4-E suggests that the EOS may be derived from the malignant clone in this leukemia. These blebs are also of diagnostic in value classifying a leukemia as FAB M4-E.

Adult↗

PubMed1987

The effect of long-term marrow culture on the nonadherent Philadelphia chromosome-positive clone in chronic myelogenous leukemia: preliminary observations.

To evaluate the effect of long-term culture on the Philadelphia chromosome-positive nonadherent hemopoietic clone in chronic myelogenous leukemia, bone marrow aspirates from five patients were grown in culture for three to four weeks. In addition to control cultures, samples were incubated with recombinant alpha-interferon. Cytogenetic studies performed on the nonadherent hemopoietic cells demonstrated suppression of the Philadelphia chromosome-positive clones, and appearance of cells with normal diploid karyotype in two of the five patients studied; cells from the remaining three patients showed persistent Philadelphia chromosome-positive cells in 100% of the metaphases. Exposure to alpha-interferon did not enhance the suppression of the Philadelphia chromosome-positive clones. A good correlation was noted between in vitro results and in vivo cytogenetic response: the two patients whose in vitro studies showed diploid clones achieved complete hematologic remission and suppression of Philadelphia chromosome-positive metaphases with therapy. Our data suggest that long-term culture favors the growth of normal clones over Philadelphia chromosome-positive clones in the nonadherent hemopoietic cells of some patients with chronic myelogenous leukemia. The value of the procedure as an in vitro predictive test for residual normal stem cells and response to therapy and for autologous marrow in vitro purging needs further exploration.

Adult↗

PubMed1986

Clinical and prognostic features of Philadelphia chromosome-negative chronic myelogenous leukemia.

Between 1965 and 1982, 105 patients with a diagnosis of Philadelphia chromosome-negative chronic myelogenous leukemia were referred to our institution with minimal or no prior therapy. The median age was 63 years and 64% were males. The overall median survival from time of referral was 14 months; 53% of patients survived 1 year and only 10% survived beyond 5 years. At the time of analysis, 92 patients (88%) were dead, 56% of deaths being preceded by a blastic crisis. Compared with Philadelphia chromosome-positive disease, patients with Philadelphia chromosome-negative chronic myelogenous leukemia were older and had a significantly higher incidence of anemia, thrombocytopenia, monocytosis, marrow blasts, decreased marrow megakaryocytes and a lower incidence of basophilia and thrombocytosis. Chromosomal abnormalities occurred in 33% of patients and consisted most frequently of trisomy 8, or an additional chromosome C, loss of the Y chromosome, or abnormalities in chromosomes #5 and #7. Of nine pretreatment characteristics significantly associated with poor survival, a multivariate analysis identified four to have independent additive prognostic significance: severe thrombocytopenia, hemoglobin levels less than 10 g/dl, increasing peripheral blasts and promyelocytes, and age 60 years or older. Monocytosis was not of prognostic significance. The derived prognostic model divided patients into three risk groups, low, intermediate, and high, with median survivals of 36, 16, and 3 months, respectively. The authors conclude that Philadelphia chromosome-negative chronic myelogenous leukemia is a distinct entity among the myeloproliferative syndromes with characteristic clinical and laboratory features and a poor prognosis. Prognostic factors and related risk categories were demonstrated within this disease entity.

Adolescent↗

PubMed1986

Spontaneous cure of end-stage acute nonlymphocytic leukemia complicated with chloroma (granulocytic sarcoma).

Spontaneous regression of end-stage acute nonlymphocytic leukemia (ANLL) complicated with chloroma (granulocytic sarcoma) was observed in a child after the patient had been sent home for terminal care. The patient was initially found to have the 8;21 translocation and has survived without any evidence of disease 101 months after the initial diagnosis and 80 months after the discontinuation of all therapy. Spontaneous regression of a wide variety of tumors has been reported, but this observed case has no features in common with those cases. Special implications of this case are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1986

Chromosomal abnormalities in lymphoma and their correlations with nucleic acid flow cytometry.

Cytogenetic studies were performed on 25 samples obtained from 25 patients with lymphoma. Fourteen of these were also simultaneously studied with nucleic acid flow cytometry to determine percent S-phase and DNA content (ploidy). In 17 cases (68%), evaluable metaphases were obtained. The evaluable metaphase rate was higher in previously untreated patients (15/19 or 79%). All but two cases showed abnormal karyotype. All five cases showing either the t(8;14) or t(8;22) abnormality were associated with extremely high percent S-phase values, ranging from 36% to 47%, which is in the range of high-grade lymphomas according to our previous experience. Four of these cases were diagnosed as Burkitt's lymphoma and one as diffuse large cell lymphoma. Further review of this latter case resulted in the pathologic diagnosis being changed to Burkitt's lymphoma. Three patients had either numerical or structural abnormalities of chromosome #21 [two cases of extra chromosomes and one i(21q)]. All three cases were diagnosed as diffuse large cell lymphoma. Four instances of trisomy 12 were identified. Only one of these was diagnosed as diffuse well-differentiated lymphocytic lymphoma. The remaining three were Burkitt's lymphoma in two and diffuse large cell lymphoma in one. Two instances of t(14;18) were observed. This is the characteristic abnormality of follicular lymphomas. One of these cases was a follicular large cell lymphoma. The second case had possibly originated from a follicular mixed lymphoma and had evolved into a diffuse mixed cell type. Both of these cases had low S-phase values in the range of low-grade lymphomas. The correlation between ploidy as determined by flow cytometry and cytogenetic analysis was good whenever the DNA index was elevated. However, when the DNA index was 1.0 (diploid), concordant measurements were observed in only five of eight cases. Flow cytometry detected one instance of clearly abnormal ploidy, which was thought to be diploid by cytogenetics. This case most likely represents a "false negative" cytogenetic determination.

Adolescent↗

PubMed1986

Acute promyelocytic leukemia. M.D. Anderson Hospital experience.

Sixty patients with acute promyelocytic leukemia were treated between 1973 and 1984. The overall median survival was 16 months with a five-year survival rate of 31 percent. The complete remission rate was 53 percent and was similar whether they received amsacrine- or anthracycline-based regimens (60 percent versus 51 percent). The median remission duration was 29 months. At five years, 43 percent of patients with responses to treatment had continuous remission and 57 percent were alive. Salvage therapy produced remissions in 53 percent of patients during first relapse, with two long-term survivors after further consolidation with bone marrow transplantation. Early fatal hemorrhage associated with disseminated intravascular coagulopathy during induction therapy occurred in 16 patients (26 percent). Multivariate analysis of the pretreatment patient characteristics significantly associated with an increased risk of fatal hemorrhage identified four that have primary prognostic importance: thrombocytopenia, elevated absolute blast and promyelocyte counts, old age, and anemia. Patients having up to two unfavorable features had a low risk of fatal hemorrhage compared with those who had more than two (5 percent versus 58 percent; p less than 0.0001). Overall, patients who received heparin had a lower incidence of fatal hemorrhage than those who did not (19 percent versus 32 percent). Heparin therapy was not beneficial to those at low risk but was associated with a trend towards decreased hemorrhagic deaths among high-risk patients (45 percent versus 67 percent). Cytogenetic studies demonstrated the characteristic 15;17 translocation in 73 percent of patients with analyzable metaphases, whereas 12 percent had other karyotypic abnormalities. Remission induction was often associated with a gradual atypical morphologic evolution into remission without intermediate hypoplasia with the interim marrows showing a high proportion of blasts. It is concluded that acute promyelocytic leukemia is a unique disease with a high potential for cure. Knowledge of its prognosis using present frontline and salvage therapy, of the factors related to fatal hemorrhage, and of the unusual patient marrow profiles during remission induction may improve the therapeutic approach.

Aminoacridines↗

PubMed1986

Therapy-related leukemia and myelodysplastic syndrome: clinical, cytogenetic, and prognostic features.

One hundred twelve patients who developed acute leukemia or a myelodysplastic syndrome (MDS) after chemotherapy or irradiation for another malignancy were reviewed. The median time from initial therapy to development of secondary leukemia or MDS was 71 months (range, 7 to 331 months). The initial malignancy was hematologic in 43%. An MDS presentation occurred in 57 patients (51%), 55% of whom subsequently transformed to acute leukemia. Chromosomal abnormalities were documented in marrow specimens from 70 of 89 patients with analyzable metaphases (79%; 69% of the total group). Compared with 34 patients with metachronous secondary leukemia without prior chemotherapy or irradiation, those with therapy-related leukemia exhibited a significantly higher frequency of abnormalities of chromosomes 5 and/or 7 (43% v 18%), and lower incidence of diploid karyotypes (18% v 50%). Chromosome 5 and/or 7 abnormalities were also significantly higher in patients previously treated with alkylating agents, procarbazine, and nitrosoureas (72% to 83%), compared with those who had received cyclophosphamide-based regimens (29%), other chemotherapies (14%), or irradiation alone (29%). The median overall survival from diagnosis of the secondary leukemia or MDS was 30 weeks. Survival was significantly shorter for patients with acute leukemia compared with MDS presentation (21 v 45 weeks); in the latter category, it was similar whether evolution to acute leukemia occurred or not. Of 72 patients treated with antileukemia therapy, 29% achieved complete remission (CR). A multivariate analysis of prognostic factors demonstrated the cytogenetic pattern to be the most important characteristic determining remission rate and survival. Other important prognostic features were the morphologic presentation (MDS v acute leukemia) for probability of achieving remission, and patient age and marrow blasts percentage for survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

Loss of the Y chromosome in acute myelogenous leukemia: a report of 13 patients.

Thirteen male patients with acute myelogenous leukemia who, on bone marrow chromosome analysis, were missing all or part of the Y chromosome were treated at this institution between 1975 and 1983. Giemsa-banding techniques were performed in 12 cases. Twelve showed -Y in at least 80% of bone marrow metaphases, and one patient had 25% 46,XYqh-. The loss of the Y chromosome was the sole karyotypic abnormality in nine patients, and the remaining four had additional chromosome changes. The peripheral blood lymphocytes were diploid in all except three cases, where no mitotic cells were recovered. The median age was 55 years, eight patients had acute myelogenous leukemia (M2) and five acute myelomonocytic leukemia (M4). Six patients (46%) had an antecedent hematologic disorder. Eleven patients received standard induction combination chemotherapy. Complete remission was achieved in seven patients (63%). Remission bone marrow chromosome analysis showed 100% 46,XY in all seven cases. The median durations of complete remission and survival were 10 months and 12 months, respectively. The review suggests that -Y is a consistent, although uncommon, chromosome marker in acute myelogenous leukemia, associated with an aggressive clinical course and intermediate prognosis.

Adolescent↗

PubMed1985

E rosette-positive agar colonies containing the Philadelphia chromosome in chronic myeloid leukaemia.

In an attempt to document possible T-cell involvement in chronic myeloid leukaemia, E rosette-positive colonies (ERPC) were grown in agar culture using a T-cell-conditioned medium. Colonies were grown from whole mononuclear cells (WMN), nonadherent E rosette-positive (NAT+) and nonadherent E rosette-negative (NAT-) cells. Cells collected from the colonies after 10 d in culture were 99-100% E rosette-positive. 8 metaphases were obtained from both NAT+ and NAT- ERPCs. In NAT- ERPCs, 5 out of 8 metaphases were positive for the Philadelphia (Ph1) chromosome as compared to 1 Ph1 positive out of 8 metaphases in the NAT+ ERPCs. These results suggest that, at least in this particular patient we studied, a subpopulation of E rosette-positive cells derived from the NAT- cell fraction express the Ph1 chromosome.

Adult↗

PubMed1985

A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22).

Twenty-six patients with inv(16)(p13q22) or del(16)(q22) in association with acute myelomonocytic leukemia (AMML-M4, FAB classification), and abnormal marrow eosinophils have been treated at this institute. Initial bone marrow eosinophilia (greater than or equal to 4%) was observed in 22 of 26 patients (85%), and abnormal eosinophil morphology, characterized by immature cells with some interspersed basophilic granules, was evident in 26 of 26 (100%). Giemsa-banded chromosome analysis performed in all patients revealed 16 cases with inv(16)(p13q22) alone, and ten cases with additional chromosome changes. Twenty-five patients received combination induction chemotherapy, and 23 (92%) achieved complete remission (CR). The median duration of remission was 18 months (range, six to 72 + months), and the median duration of survival was 34 months (range, 0.5 to 133 months). Nine patients (35%) relapsed in the CNS at a median time of 19 months (range, six to 133 months) from first marrow CR. All patients had leptomeningeal disease, and in addition, six of nine (66%) demonstrated two or more enhancing lesions on computed tomography brain scan, consistent with intracerebral myeloblastomas. Review of 384 Giemsa-banded patients with acute myeloid leukemia revealed no other morphologic or cytogenetic subgroup with either an equivalent incidence of CNS leukemia or documented intracerebral myeloblastomas. This series of inv(16)(p13q22)/del(16)(q22) AMML reports a favorable prognosis for such patients and associates a specific clonal cytogenetic subgroup of acute leukemia with a distinct propensity for CNS relapse, manifesting as leptomeningeal disease and intracerebral myeloblastomas.

Adult↗