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.

Acute lymphocytic leukemia of the ovary: the value of sonography.

Leukemic involvement of ovary has been found in up to 30% of patients with acute lymphocytic leukemia (ALL) at autopsy, but is rarely found clinically. Since the ovary may be a sanctuary for ALL to reseed the marrow, early clinical detection of ovarian involvement is important. The use of sonography in evaluating the ovary is suggested as part of the management routine in ALL. It can be used prior to cessation of chemotherapy and on subsequent follow-up to assess the state of the ovary. A case is presented in which a young woman with ALL in remission developed a pelvic mass, documented by ultrasound, subsequently shown to represent leukemic infiltration of the ovary.

Ovarian tumor as manifestation of relapse in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) was initially diagnosed in a 12-year-old girl. Maintenance chemotherapy was discontinued after 32 months of continuous remission. Relapse of ALL occurred ten months after cessation of chemotherapy. Twenty-one months after relapse, she presented with a large ovarian tumor due to leukemic infiltration while her bone marrow and central nervous system (CNS) were still in remission. She remained in bone marrow and CNS remission when disseminated leukemic infiltration of the peritoneum was found seven months later. She died of bone marrow relapse 11 months after ovarian relapse, six years and two months after the initial diagnosis. In contrast to testicular relapse, ovarian relapses in acute lymphoblastic leukemia are rarely reported.

Non-Hodgkin's lymphomas in leukemic phase: clinicopathologic correlations.

A leukemic phase occurred in 30 (14 percent) of 214 patients with non-Hodgkin's lymphoma. To determine the significance of peripheral blood involvement in each type of NHL, patients were subdivided according to a modified Rappaport classification. Each histologic subtype presented a homogeneous clinical picture which differed from that seen in other histologic subtypes. Of particular note was the recognition of two distinctive cytologic and clinical subtypes within the category of nodular lymphoma, poorly differentiated lymphocytic lymphoma (NPDL). In one subtype, the predominant cells had cytologic features akin to those of lymphoblasts. In these cases, although the interval to peripheral blood involvement was variable, the median leukemic survival was only two months. In contrast in conventional NPDL the median leukemic survival was 43+ months, and peripheral blood involvement did not appear to exert an independent effect on prognosis. In diffuse large cell lymphomas the median leukemic survival was 0.5 months, with peripheral blood involvement appearing as a terminal event associated with unresponsive disease in multiple sites. The recognition of adult lymphoblastic lymphoma as a clinicopathologic entity with a high risk of leukemic conversion, 100 percent in this study, is also confirmed.

Malignant lymphoma of pre-T-cell type terminating in acute myelocytic leukemia. A case report with enzymic and immunologic marker studies.

We report a case of a T-zone malignant lymphoma of a cervical lymph node developing in a 25-year-old man. Only 14% of the marrow was originally involved, but within two months massive, leukemic dissemination ensued. The blast cells were unable to bind sheep erythrocytes (E) but expressed human thymus leukemia antigen (HTLA) and common ALL-stem-cell (cALL) antigen and had high terminal deoxynucleotidyl transferase (TdT) and acid phosphatase activity. These findings suggest a malignant lymphoproliferative disorder of pre-T-cell type. Complete remission was achieved with intensive chemotherapy. Two months later, acute myelomonocytic leukemia was diagnosed; at this time, over 90% of the blast cells were peroxidase, sudan black, and chloracetate-esterase positive. Consistent with loss of high TdT activity and HTLA and cALL antigens, 86% of the blasts now expressed Ia-like antigens. Cytogenetic studies demonstrated hyperdiploidy. Reports of granulocytic leukemia in lymphoma are reviewed in the context of the above findings and the hypothesis that a leukemogenic factor affects a multipotential stem cell.

Isolated pulmonary leukemic relapse following successful bone marrow transplant in a child with acute lymphoblastic leukemia.

Leukemic relapse and interstitial pneumonitis are common complications for leukemic patients following bone marrow transplantation. We present the case of a successful bone marrow transplantation patient who developed an interstitial infiltrate on chest roentgenogram 212 days post-transplant that was diagnosed by open lung biopsy and found to be a leukemic relapse of the lung parenchyma. No extrapulmonary sites were involved and the infiltrate cleared in three weeks with systemic chemotherapy. Pulmonary function tests continued to demonstrate restrictive disease. The patient remained in remission for nine months following pulmonary relapse on systemic chemotherapy. This patient illustrates an unusual site of leukemic relapse and the importance of open lung biopsy in the diagnosis of the immunosuppressed patient with a pulmonary infiltrate.