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PubMed1998

The clinical indications for identical pathogenesis of isolated and non-isolated testicular relapses in acute lymphoblastic leukaemia.

In the present population-based study, we compared the clinical data of testicular relapses with and without concurrent bone marrow relapse and clinical data of the relapses in other locations among boys with acute lymphoblastic leukaemia (ALL), in order to study the possible evidence of early sequestration and local regulation of leukaemic lymphoblast in the testis of humans. The results suggest that the pathogenesis of isolated testicular relapse (T) and testicular relapse with a concurrent bone marrow relapse (T + BM) is likely to be similar. Isolated and non-isolated testicular relapses appeared late after the achievement of remission (T 34 +/- 16 months, T + BM 32 +/- 15 months) in ALL compared to relapses in other locations (CNS 23 +/- 11 months, BM 25 +/- 19 months). The better prognosis after testicular relapses (estimated second event free survival probability, 2-EFS: T 0.63, T + BM 0.32) compared to bone marrow relapse (2-EFS: BM 0.13) further suggests that testicular relapse with a concurrent bone marrow relapse possibly originates from the isolated testicular relapse, and that the isolated testicular relapse is a separate entity and not a manifestation of systemic recurrence. Higher frequencies of isolated and non-isolated testicular relapses (T 9%, T + BM 5%) were observed among boys with onset of ALL in early puberty (10-12 y) compared to those among younger (T 4%, T + BM 2%) and older (T 0%, T + BM 0%) boys. The late occurrence, the possible association with hormonal maturation and the good prognosis after testicular relapses suggest a possible local regulation of the residual leukaemic lymphoblast in human testis.

Adolescent↗
PubMed2004

Relapsed acute leukemia in children: Oman experience.

Acute leukemia (AL) is the most common malignancy in children in Oman. It accounts for over one-third of all childhood cancers, most of which (approximately 75%) are acute lymphoblastic leukemia (ALL). Over a decade, a total of 128 cases of childhood acute leukemia have been diagnosed and managed at Paediatric Haematology/Oncology Unit, Sultan Qaboos University Hospital, which is the national referral center of pediatric leukemia cases. A retrospective review of case notes was used to study all children with a diagnosis of acute leukemia from January 1993 to January 2003. All the cases were diagnosed using a bone marrow aspirate with morphological and immunophenotypic classification. Over this period, 24 cases relapsed. They were classified as per BFM group as "very early," "early," and "late" according to the time from diagnosis to first relapse and were divided into isolated bone marrow (BM), extramedullary site, and combined relapse. Sixteen percent of ALL cases and 58.6% of acute myeloid leukemia (AML) cases so far relapsed. Most of the AML cases relapsed very early on in treatment. Eleven patients had combined relapse in BM and extramedullary site (9 in the central nervous system, 1 in the testicles, and 1 in the eye). The overall outcome of these patients is very poor, and only 6 patients out of 24 are still alive. In conclusion, the relapse rates of childhood AL are more or less similar to those of other reports but the overall outcome is very poor. A large majority of the patients in this study are either very early or early relapsers. Future studies including genetic and molecular analysis may be able to explain the difference in clinical outcome of these relapsed AL cases.

Acute Disease↗
PubMed2006

Unusual extramedullary recurrences and breast relapse despite hepatic GVHD after allografting in Ph+-ALL.

Extramedullary recurrences with or without bone marrow involvement are reported in up to a half of leukemic relapses after BMT. Our report describes a case of an extramedullary recurrence and breast relapse after second-allografting in a female patient with Ph+-acute lymphoblastic leukemia (ALL), occurring when there was active hepatic GHVD. This case illustrates the complex relationship between graft-versus-host disease (GVHD) and graft-versus-leukemia since she had no evidence of leukemia in her marrow demonstrating 100% full-donor chimerism while she had ALL relapse in her breast.

Breast↗
PubMed2002

Leukemic leptomeningeal involvement in stage 0 and stage 1 chronic lymphocytic leukemia.

Central nervous system (CNS) involvement in early (Rai Stage 0 and Stage 1) chronic lymphocytic leukemia (CLL) is rare, with only five cases reported. We present the sixth reported case, a 77-year-old male with a 4 year history of Stage 0 CLL who presented with sudden onset of diplopia and headache. Workup revealed a leukemic involvement of his CNS and he responded well to treatment with intrathecal (IT) methotrexate. After his third IT treatment, he developed a change in his mental status, consistent with a chemotherapy induced encephalopathy, which was effectively treated with IT hydrocortisone. In addition to the case presentation, we review the previously reported cases in an effort to determine any characteristics common among the Stage 0/1 CLL patients with reported CNS involvement.

Aged↗
PubMed2003

Extramedullary relapse in the pleura in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloblastic leukemia with specific clinical, morphologic and genetic features and a good response to all trans retinoic acid (ATRA). However, extramedullary (EM) relapse is an interesting feature of these cases, especially those treated with ATRA. Recently, we have encountered an EM relapse in the pleura in a case with APL receiving an ATRA containing regimen. This case is reported and the relevant literature is reviewed.

Adult↗
PubMed2003

Coexistence of chronic lymphocytic leukemia and essential thrombocythemia.

The association of chronic lymphocytic leukemia (CLL) with essential thrombocythemia (ET) is an extremely rare event and until now 3 patients with such coexistence have been reported in the literature. We report a 77-year-old white woman in whom these two disorders were diagnosed concomitantly on the basis of peripheral blood count and cytology, bone marrow cytology and histology, immunophenotyping, as well as exclusion criteria. The diagnosis of ET was also supported by spontaneous in-vitro erythroid colony growth and by evaluation of thrombopoietin (TPO) serum level. Interphase FISH analysis allowed to detect 13q14.3 deletion in 98% of lymphocytes nuclei. In contrast this aberration was not observed in the megakaryocytes. The results of PCR analysis of IgG gene rearrangement showed distinct bands characteristic for monoclonal lymphoid population in bone marrow, peripheral blood and inguinal lymph node. The patient was started on hydroxyurea 1 g/day and normalization of the platelet count was achieved. Possible etiopathogenic relationships between both disorders and differential diagnosis of ET and reactive thrombocytosis (RT) are discussed.

Aged↗
PubMed2003

Acute myelogenous leukemia with splenic infarcts presenting as fulminant multi-organ failure.

A 60-year-old male was admitted with leukopenia, thrombocytopenia, splenic infarcts and a normal peripheral smear. Within few hours he rapidly deteriorated with fatal multi-organ failure. Autopsy revealed massive infiltration of leukemic cells in several organs. Acute myelogenous leukemia should be considered in a patient presenting with unexplained multiorgan failure.

Humans↗
PubMed2004

Atopic dermatitis-like non-erythrodermic leukemic variant of CD3(-/+dim) CD4(+) cutaneous T-cell lymphoma preceded by cutaneous papular xanthomatosis.

We report a patient with cutaneous papular xanthomatosis who 4 years later developed a CD3(-/+dim)/CD4(+) T-cell lymphoma. Pruritic xerotic non-erythrodermic skin, eosinophilia and hyper-IgE were present and erroneously classified as atopic dermatitis. Flow cytometry and DNA ploidy analysis of both blood and skin lymphocytes, skin histology and blood T-cell receptor gene rearrangement studies confirmed diagnosis of T-cell lymphoma. Monoclonal CD3(-/+dim)/CD4(+) T-cells were especially prone to the synthesis of IL-13, a cytokine that is involved in IgE-secretion, and comprised both a medium (diploid) and large (hyperploid) sized T-cell populations with a similar immunophenotype. The majority of the normal residual T-cells were large granular lymphocytes, expressed activation-related and natural-killer-associated markers and secreted high levels of interferon gamma, suggesting that they might correspond to active cytotoxic cells directed against the neoplastic T-lymphocytes.

Adult↗
PubMed2004

Presentation of extramedullary acute myelogenous leukemia as bilateral testicular masses: response to non-myeloablative allogeneic transplantation.

We present an unusual case of extramedullary acute myelogenous leukemia (AML) presenting as bilateral testicular masses. The patient subsequently developed diffuse skin lesions and bone marrow involvement. Although he had only a partial response to intensive chemotherapy, the patient obtained a complete remission after non-myeloablative allogeneic transplantation.

Aged↗
PubMed2005

Simultaneous presentation of acute monoblastic leukemia and mantle cell lymphoma: case report and review of the literature.

This paper reports a 73-year old woman with simultaneous presentation of acute monoblastic leukemia (acute myeloid leukemia (AML), French-American-British (FAB) type M5a) and mantle cell lymphoma. The patient presented with wasting, generalized lymphadenopathy, an extensive infiltrative rash and pancytopenia. Bone marrow and lymph node histopatholology showed extensive infiltration by leukemic monoblasts. Marrow cytogenetics revealed a complex karyotype, including t(8;16)(p11;p13). Flow cytometric immunophenotyping of peripheral blood, lymph node and bone marrow demonstrated two populations, expressing CD5, CD19, CD20 and CD22 and CD45, HLA-DR, CD13, CD33, CD14 and CD38, respectively. A focus of abnormal lymphocytes in the lymph node biopsy demonstrated BCL1 expression and t(11;14)(p11;p13) by fluorescence in situ hybridization and immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction. The patient received infusional cytarabine, daunorubicin and etoposide chemotherapy, with complete remission of both the AML and the mantle cell leukemia. To the authors' knowledge, this is the first report of simultaneous presentations of AML, FAB M5a and mantle cell lymphoma. The case is discussed and the literature is reviewed.

Aged↗
PubMed1999

Improvement of quality of life after splenectomy in an HTLV-I carrier with T-cell prolymphocytic leukemia.

A 34-year-old woman of HTLV-I carrier with T-PLL, whose quality of life improved and survival was prolonged after splenectomy, is described. The patient had marked splenomegaly, generalized lymphadenopathy and marked proliferation of abnormal lymphocytes in the peripheral blood with an irregular nucleus, deeply basophilic cytoplasm and a single prominent nucleolus, which were positive for CD2, CD3, CD5, CD7, CD4 and CD8. Although the patient had serum antibody against HTLV-I, HTLV-I proviral DNA integration was not detected. She was diagnosed as an HTLV-I carrier with T-PLL and received combination chemotherapy and 15.1 Gy splenic irradiation. However, the generalized lymphadenopathy and splenomegaly did not improve. The patient underwent splenectomy to palliate abdominal distension and hypersplenism. After the operation, her symptoms improved dramatically and within a week her hemoglobin concentration and platelet count normalized. She was discharged from hospital two weeks after the splenectomy, however 11 months later, she relapsed and despite treatment with chemotherapy and alpha-interferon, she died two months after the second admission. Autopsy findings revealed that PLL cells had invaded the bone marrow, lymph nodes, liver, lungs, kidneys, uterus, ovaries and adrenal glands.

Adult↗
PubMed1984

Adult T-cell leukemia: clinical and immunologic characterization of a nonendemic case.

A 56-year-old black man with nonendemic adult T-cell leukemia is reported, who presented with severe hypercalcemia and leukemic leptomeningeal infiltration but had no evidence of bone marrow involvement. His malignant cells were characterized by light and transmission electron microscopy, cytogenetics, and flow cytometry. The cells demonstrated the deeply indented or convoluted nuclei characteristic of endemic human T-cell lymphoma virus-associated cases. Surface phenotyping indicated the cells' origin to be from the mature, helper/inducer subset of T-lymphocytes. However, there was no clinical or laboratory evidence that the malignant cells retained immunoregulatory function. The clinical and immunologic features of this and other nonendemic cases are compared with those of patients from the endemic regions of Japan, the Caribbean islands, and the southeastern United States.

Biopsy, Needle↗
PubMed2006

Extramedullary disease and targeted therapies for hematological malignancies--is the association real?

During the past years targeted therapies have gained a major role in the treatment of cancer patients, including those with hematological malignancies. Extramedullary involvement is a rare manifestation of acute and chronic leukemias and of multiple myeloma. Nevertheless, with the expanding use of targeted treatments there is an impression that the incidence of extramedullary relapses is increasing. We reviewed the reports on this phenomenon in patients treated with all-trans-retinoic acid and arsenic trioxide for acute promyelocytic leukemia, thalidomide and bortezomib for multiple myeloma and imatinib for chronic myeloid leukemia. The pathogenetic mechanisms suggested are: life prolongation by these treatments allowing for disease progression arising from dormant cells; poor penetration of the drugs to sanctuary sites like the central nervous system; the requirement of some of these drugs, especially thalidomide, for the marrow microenvironment to exert their action; and finally, a possible active role for some of the drugs, like all-trans-retinoic acid. Since the use of these targeted therapies is expanding we should be aware of this association.

Antineoplastic Agents↗
PubMed1998

Cognitive and academic late effects among children previously treated for acute lymphocytic leukemia receiving chemotherapy as CNS prophylaxis.

OBJECTIVE: Examine cognitive and academic late effects among children and adolescents who had received central nervous system (CNS) prophylactic chemotherapy alone for acute lymphocytic leukemia (ALL); none had received whole brain radiation therapy (RT). METHOD: Subjects included 47 children and adolescents from 5 to 22 years of age who were treated on the same protocol and had been off treatment from 2 to 7 years at the time of assessment. RESULTS: As a group the survivors displayed generally average performance on measures of cognitive and academic abilities, although they differed from normative means on tests of nonverbal skills. Girls performed more poorly than the normative sample on nonverbal tasks, while no differences were found for boys. Age at diagnosis and time off treatment were not significantly associated with cognitive and academic functioning for survivors of this particular chemotherapy-only protocol. CONCLUSIONS: Data were interpreted to support generally modest potential late effects in specific areas for children and adolescents surviving ALL. These findings suggest a need for monitoring nonverbal cognitive skills for childhood survivors of ALL, particularly for girls.

Achievement↗
PubMed1996

Merkel cell carcinoma diagnosed by fine-needle aspiration.

Merkel cell carcinoma is a relatively rare neoplasm of the skin. The present study describes three cases of Merkel cell carcinoma diagnosed by fine-needle aspiration cytology and reviews their histologic, cytologic, and ultrastructural features. The advantages of using fine-needle aspiration to diagnose Merkel cell carcinoma (and other cutaneous neoplasms) are emphasized.

Aged↗
PubMed2002

A case of acantholytic dermatosis and leukemia cutis: cause or effect?

Leukemia cutis is capable of presenting in a variety of clinical and histologic guises. We describe a 75-year-old man with a recent diagnosis of M0 acute myelogenous leukemia, who presented with multiple pruritic erythematous papules on his chest and back. Microscopically, the epidermis showed acrosyringeal-based acantholysis consistent with transient acantholytic dermatosis (TAD), associated with exocytosis of atypical hematolymphoid cells. In addition, the dermis showed a contiguous atypical hematolymphoid proliferation consistent with conventional leukemia cutis. To our knowledge, this is the first such case combining features of TAD with leukemia cutis. It remains to be determined whether the acantholysis occurred secondary to the leukemia cutis, was initiated by the migration of leukemic cells, or if the association is merely serendipitous.

Acantholysis↗