Eva Hvizdala

A staging system for histiocytosis X: A southwest oncology group study

Patients with generalized histiocytosis X may be divided into three prognostic groups based on age at the time of diagnosis and presence or absence of organ dysfunction. These variables are independent. Favorable response to initial chemotherapy was shown to be associated with improved survival and overall disease control.

Pediatric oncology group experience with modified LSA2-L2 therapy in 107 children with non-Hodgkin's lymphoma (Burkitt's lymphoma excluded)

From September 1976 to August 1979 the Pediatric Oncology Group accessed 145 children to study the effectiveness of modified LSA2‐L2 therapy for the treatment of non‐Hodgkins lymphoma (NHL). Burkitts lymphoma patients were ineligible; E‐rosette‐positive patients with ≥ 25% blasts in the marrow entered after February 1977 were reported separately. Radiotherapy could be used to treat patients with compressive mediastinal disease at diagnosis and was prescribed for those with residual abdominal disease as demonstrated by second‐look surgery on completion of induction chemotherapy. Confirmation of diagnosis by the Pathology Panel and Repository Center for Lymphoma Clinical Trials was mandatory. Diagnostic tissues of 131 patients were reviewed. Among 107 evaluable patients, 91 (85%) achieved complete remission. Differences in response rates among the three major histologic groups (lymphoblastic, undifferentiated, and large cell) were of statistical significance, with response being poorest for diffuse undifferentiated lymphoma (P = 0.03). Failure‐free survival did not differ significantly for the three major histologic diagnoses. While response rate was lowest for Murphy Stage III patients (79%), the differences among the stages were not significant. Stage was not a significant prognostic factor for failure‐free survival (P = 0.08). The number of patients still at risk and the Kaplan‐Meier estimate of percentage of patients remaining at risk after 3 years is: Stage I, 8 (100%); Stage II, 10 (67%); Stage III, 28 (57%); Stage IV, 6 (39%); and > 25% blasts, 1 (13%). Stage III failure curves for lymphoblastic disease show continuing stepwise failure through 3 years. Among patients with diffuse large cell and undifferentiated disease, most failures occurred by 8 months. M1 and M2 levels of marrow involvement were not prognostic among children with lymphoblastic disease. The presence of a mediastinal mass was a significant factor contributing to failure in children with lymphoblastic disease without marrow involvement. Leucocytosis > 10,000/1, was a significant (P = <0.001) factor predicting failure‐free survival for patients with large cell lymphoma. The delivery of radiotherapy was not a significant factor in achieving remission. No consistent benefit resulted from using radiotherapy to treat postinduction residual disease demonstrated on second‐look exploration. The LSA2‐L2 regimen was associated with considerable toxicity, severe or worse in 77% and life‐threatening to 40% of these patients. Four died of toxicity. However, therapy was given more easily and safely as investigator experience increased. Maintenance therapy was delivered on an out patient basis without complications in most instances. This study demonstrates the ability of the LSA2‐L2 regimen to produce long‐term remissions, or to “cure” 60% to 70% of children among the major histologic categories of childhood NHL, excepting Burkitts lymphoma. Long‐term survival, or “cure”, occurs in 90% with Stages I and II disease and some 50% of those with Stages III and IV disease. Neither radiotherapy nor second‐look surgical procedures appear to influence outcome. The continuous relapse pattern seen in lymphoblastic disease involving the mediastinum suggests the need for more intensive repetitive therapy “up‐front”. The relapse pattern of non‐lymphoblastic disease suggests the discontinuation of therapy after 1 year.

A morphologic study of childhood lymphoma of the lymphoblastic type: the pediatric oncology group experience

For this study 227 non‐Hodgkins lymphomas, registered through the Pediatric Oncology Group clinical studies between 1976 and 1982, were morphologically subclassified into major histologic types and subtypes, and their histopathologic and clinical features were compared. These lymphomas were distributed primarily into only three of the recognized major histologic types: lymphoblastic (LB), 106 (47%) undifferentiated (DU), 49 (21%); and diffuse histiocytic (DH), 72 (32%). These patient groups were found to differ in several ways: (1) the LB lymphomas contained most of the patients under two years of age; (2) the LB lymphomas tended to present in higher clinical stages; (3) the LB lymphomas tended to involve lymph node groups and the bone marrow more often than did the DU and DH lymphomas; and (4) the DU lymphomas had a greater tendency for gastrointestinal tract and other major organ system involvement. The complete remission rate of 96%, for the LB lymphomas was better than for either the DU or the DH lymphomas. The disease‐free survival of the LB lymphomas was significantly better than the DU group, but not the DH group. The LB were histologically divisible into three subtypes: convoluted (C), nonconvoluted (NC), and large cell variant (LCV). The C and NC subtypes preferentially involved the mediastinum and peripheral lymph nodes initially, while the LCV tended to involve the abdomen. However, none of the subtypes differed in clinical stage. The complete remission, and the disease‐free survival rates between these subtypes were not statistically different. Cancer 59:1126‐1131, 1987.

Enuresis in sickle cell disease

The prevalence of enuresis and management options for this condition were studied in our population of sickle cell patients. A total of 91 active patients (6 to 21 years old) followed at our regional sickle cell center was surveyed for the symptoms of primary nocturnal enuresis. Of the 91 patients 27 (29.6%) had primary nocturnal enuresis. Of those with enuresis 17 had homozygous sickle cell anemia, 5 had hemoglobin sickle cell disease, 4 had sickle cell beta + thalassemia and 1 had sickle cell beta zero-thalassemia. Of 10 patients who elected to receive intranasal desmopressin acetate 6 (60%) had complete or partial resolution of nocturnal enuresis. Our data confirm the high prevalence of nocturnal enuresis in patients with sickle cell disease and support the role of desmopressin acetate in the treatment of these patients.

A morphologic study of childhood lymphoma of the undifferentiated type the pediatric oncology group experience

A retrospective analysis of 49 cases of undifferentiated non‐Hodgkins lymphoma, registered through the Pediatric Oncology Groups randomized clinical trials between 1976 and 1982, suggests that the histologic distinction between Burkitts and non‐Burkitts tumor is clinicopathologically irrelevant in children. Patients with undifferentiated lymphoma were stratified morphologically into three subtypes: Burkitts (B; 18 patients); non‐Burkitts (NB; 21 patients); and small noncleaved, not‐otherwise‐specified (NOS; 10 patients). Median age at presentation was 10 years for B; 12 years for NB; 6 years for NOS; and 10 years overall. Univariate analysis of clinical and laboratory data at presentation, yielded no significant differences between B, and NB patients. Complete remissions were obtained in 75% of the patients, and there were no significant differences in complete remission rate among the different morphologic subtypes of undifferentiated lymphoma. There were no significant differences in the estimated disease free survival between B, and NB patients. No morphologic parameters were identified that were predictive of prognosis. Cancer 59:1132‐1137, 1987.

A morphologic study of childhood lymphoma of the diffuse “histiocytic” type the pediatric oncology group experience

Of 227 cases of pediatric non‐Hodgkins lymphoma with adequate histopathologic material for review, 72 (32%) were classified as diffuse “histiocytic” lymphoma (DHL). These cases were further divided into different morphologic subtypes according to the Lukes—Collins classification, and the National Cancer Institute Working Formulation, to ascertain whether there were any significant prognostic differences among the different subtypes. The results of our study showed that 40 patients were classified as immunoblastic lymphomas, and 32 were called large follicular center cell (FCC) tumors. Of the 40 patients with immunoblastic histology, 19 had morphologic features of the clear cell type and were interpreted as consistent with T‐immunoblastic lymphomas; an additional two had polymorphous features also consistent with T‐cell type: 17 had plasmacytoid features, and were morphologically classified as B‐immunoblastic lymphomas; two could not be subtyped. Of the 32 patients with morphologic features of FCC lymphomas, 29 were classified as large noncleaved type, and three as large cleaved type. A clinicopathologic analysis showed that 90% of the patients obtained complete remission, and there were no significant differences in complete remission rate among the different morphologic subtypes of DHL. The estimated five year disease‐free survival for all patients was over 70%, with no failure after the second year; and there were no significant differences in the disease‐free survival among the different subtypes. The only clinical differences that we found, were that patients with lymphomas of FCC (large noncleaved) type (1) were younger (P = 0.01); (2) had less nodal involvement (P = 0.03); and (3) had more organ involvement (P < 0.01). We conclude that the morphologic subclassification of DHL in children currently has limited clinical prognostic significance. Cancer 59:1138‐1142, 1987.

High-dose cyclophosphamide-high-dose methotrexate with coordinated intrathecal therapy for advanced nonlymphoblastic lymphoma of childhood: results of a Pediatric Oncology Group study.

The Pediatric Oncology Group (POG) investigated a high-dose cyclophosphamide (CPM) high-dose methotrexate (MTX) regimen to determine therapeutic efficacy in confirmed advanced nonlymphoblastic non-Hodgkins lymphoma (NHL) (stages III and IV) and B-cell acute lymphatic leukemia (B-ALL) in children. Another goal was to determine the comparative effectiveness of shortened maintenance treatment (2 versus 6 courses) in the study population. Systemic induction therapy included vincristine, prednisone, cyclophosphamide, and intermediate-dose MTX with leucovorin rescue. Superimposed intrathecal (IT) therapy included cytosine arabinoside for 2 successive days followed on day 3 by MTX. Intrathecal MTX was given 3 times during induction. At the end of induction, 2 days of triple (hydrocortisone, MTX, and cytosine arabinoside) therapy were given intrathecally (TIT). All patients then received a consolidation course of 4 doses of TIT, 2 doses of cyclophosphamide, and 4 more courses of vincristine and MTX with leucovorin rescue. Patients were then randomized to receive either 2 or 6 cycles of vincristine plus MTX with leucovorin rescue. The TIT was given with each cycle. Complete response rates by histology and Murphy stage (1) were as follows: undifferentiated lymphoma (DUL) stage III, 84/105 (80%): stage IV, 5/12 (42%); and other NHL [primarily large cell lymphoma (LCL)] stage III, 21/28 (75%); stage IV, 2/3 (67%). Event-free survival (EFS) at greater than 2 years was similar for patients with DUL and LCL, i.e., 65 and 61%, respectively. No significant difference in outcome was noted between patient groups receiving 2 or 6 maintenance treatments (p = .76). Treatment was notable for its modest toxicity following the early change to single-dose CPM therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive Necrotizing Myelopathy Associated With Leukemia: Clinical, Pathologic, and MRI Correlation

We describe a patient with progressive, irreversible, necrotizing myelopathy associated with myelomonocytic leukemia. The neuropathologic lesions consisted of diffuse necrosis, most pronounced in the cervical cord and affecting both the gray and white matter. These areas corresponded to areas of increased T2 on magnetic resonance imaging scans of the patient. We felt that there was no causal relationship of these lesions to any single antileukemic agent the patient received, and no other local or systemic causes were found to explain the lesions at necropsy. It is suggested that our case is an example of paraneoplastic necrotizing myelopathy. To our knowledge, this is the third case of necrotizing myelopathy associated with leukemia reported in the English medical literature, and the first one demonstrating usefulness of magnetic resonance imaging in diagnosis of necrotizing myelopathy. (J Child Neurol 1987;2:44-49).

Spontaneous remission in monosomy 7 myelodysplastic syndrome.

Hadley, A.G.. Garner, S.F. & Taverner, J.M. (1993) AutoAnalyser quantification. monocyte-mediated cytotoxicity and chemiluminescence assays for predicting the severity of haemolytic disease of the newborn. Transfusion Medicine, 3, 195-200. Hadley, A.G., Kumpel. B.M., Leader, K.A.. Poole. G.D. & Frazer, I.D. (199 1) Correlation of serological, quantitative and cell-mediated functional assays of maternal alloantibodies with the severity of haemolytic disease of the newborn. British Journal of Haematology, 77,221-228. superior to AA, we actually concluded that, in highly immunized mothers, neither assay necessarily provided information that was more useful than ultrasonography and obstetric history. Furthermore, recent work from Downing et a1 (1994, and personal communication), where AA quantitation and a CLT assay were used to study cases of severe haemolytic disease requiring intrauterine transfusion, did not find a significant correlation between fetal haematocrit and maternal anti-RhD activity, measured by either AA anti-D quantitation or CLT. Taking these observations into account, it would be interesting to know the correlation between AA and CLT results for the samples tested by Buggins et al. Furthermore, did the CLT results provide any information which clearly benefited the management of the pregnancy, beyond that already known from ultrasonography and obstetric history? In conclusion, we support the authors’ views that CLT may be superior to AA in antenatal studies. However, a cautious approach is recommended when handling results, because, so far, the prime value of the assays seems to be in providing useful advice to obstetricians and possibly in preventing unnecessary invasive procedures. As yet, no assay of maternal anti-RhD can replace fetal monitoring.

Use of hydroxyurea and recombinant erythropoietin in management of homozygous β0 thalassemia

This report describes the sustained response of an Iranian girl with homozygous beta(0) thalassemia (IVS-II-1G-->A) to hydroxyurea (HU) and recombinant erythropoietin (rEPO). Since the start of this regimen 7 years ago, she has been transfusion-independent and her hemoglobin is maintained between 9.5-11.0 gm/dL. She is maintaining consistent growth around the 10th percentile for age and enjoys a good quality of life. She has not had any therapy-related adverse effects. This experience suggests that therapy with HU and rEPO may be useful long-term in some patients with beta thalassemia.