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The majority of childhood cancer patients can expect nowadays to be cured and the percentage is now between 70% and 80%. The number of long-term survivors, off- threatment for at least 5 years, is rising rapidly and is becoming a new population, which needs a special care. It is becoming increasingly important to know how to prevent and treat the physical late effects as well as the psychosocial ones. The oldest among these patients are now in their 40's. How will their old age be like? Are they really cured? The aim of this study is to present a detailed survey of the literature on this topic as well as the authors' personal experience. Several techniques of psychological investigation for this population are highlighted. The semistructured interviews are mostly used for mono-institutional research, while the narrative dialogues are useful for small groups of patients. Questionnaires are usually conducted by epidemiologists for large groups of survivors. Tests are used for specific items such as defense mechanisms, self-esteem, relationships within the family, fear, and panic. The evaluation of the post-traumatic stress disorder is considered and the most important literature data are reported. It is also stressed the need of prevention of any type of psychosocial distress. In conclusion, most of the survivors appear to lead normal adult lives, to have obtained high school degrees, good jobs, and several have families and children. Nevertheless, a small percentage show some psychological or social problems, such as anxiety, depression, fear over the future or over relapse, a second primary, or sterility. The most vulnerable among them are females, people in poor financial conditions, the unemployed and those with poor educations.

Allogeneic bone marrow transplantation in the E.U. is a routine treatment which requires specific legal procedures to protect under-aged donors. The European Council (5/29/1978) decreed the guidelines concerning organ transplantation for the Member Countries. These guidelines included obtaining written consent from the donor or his/her guardian. The International Convention on children s rights (New York 11/20/1989, art. 12) stated that the minor has the right to give his/her opinion, which must be taken into consideration. Currently, though legal guidelines vary among Member Countries, all require the parents or guardian s written consent. In France, an ethics committee (L. 76-1181/1976) must inform the minor about the consequences of the procedure, respect his/her will and obtain consent. In Luxembourg, the Department of Health requires written consent as well as authorization by three experts, including two physicians. In Spain an ethics committee must obtain the minor s consent which is then approved by a government authority and counter-signed by a physician. In UK an N.H.S. directive (1st Aug. 1993) states that as of 16 years of age donors must give consent. In Germany minors over 14 are allowed to give consent. A legal guarantee is required when the recipient is a parent to avoid conflict of interest. In Belgium minors between 15 and 18 require witnessed written consent, counter-signed by the guardian and approved by a physician. Married donors below 21 need the consenting adult s approval. In Portugal verbal consent by the minor and the guardian is sufficient. In Denmark the guardian s written consent is needed. In Italy a law is being prepared to best protect minors. In conclusion it would be useful for the European Council to decree the detailed legal guidelines and require greater uniformity among the E.U. Countries.

In 1982, the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) started its third-generation study, aiming to improve previous results obtained by AIEOP '79 study and to deliver a standardized treatment to most Italian children with acute lymphoblastic leukemia (ALL).We treated 902 children (older than 1 year and younger than 15 years of age) with newly diagnosed ALL in multicenter studies of risk-directed therapy (111 low risk [LR] from Study 8201; 570 average risk [AR] from Study 8202; and 117 and 104 high risk [HR] from Studies 8303 and 8503, respectively). Induction therapy was composed of vincristine, prednisone, and asparaginase for LR or AR patients and these agents plus daunorubicin, (Study 8503) or vincristine, prednisone, cytarabine, and intermediate-dose methotrexate (Study 8303) for HR patients. Central nervous system (CNS) preventive therapy consisted of intrathecal methotrexate only (LR), intrathecal methotrexate plus 18 Gy cranial irradiation (AR and HR Study 8503), or high-dose (HD) cytarabine (HR Study 8303). Reinduction therapy was vincristine/prednisone/daunorubicin for AR patients with cyclophosphamide added for HR patients in Study 8303 and HD asparaginase in Study 8503. LR patients did not receive intensification therapy. Continuation therapy comprised 6-mercaptopurine plus methotrexate and monthly pulses with vincristine plus prednisone for all patients, except for HR patients in Study 8303 who also received teniposide plus cytarabine. Weekly HD asparaginase was also given in Study 8503. Duration of treatment was 24 months for Studies 8201 and 8202, 15 months for Study 8303, and 22 months for Study 8503. The overall complete remission (CR) rate was 94.7% (97.3% for LR, 94.9% for AR, and 93.2% for HR).Overall 7-year event-free survival (EFS) was 53.6% (standard error [SE], 1.8). EFS was 60.8% in LR (SE, 4.7), 60.6% in AR at 7 years (SE, 4.7), and 18.5% in Study 8303 (HR) at 5 years (SE, 3.8). Because of the poor result in HR patients, a successor study (8503) was developed that yielded a 5-year EFS of 46.1% (SE, 5.1). Site-specific relapse rates were 18.5% (LR), 13.4% (AR), 35.1% (HR on 8303), and 18.3% (HR in Study 8503) for bone marrow and 9.2%, 7.9%, 17.5%, and 19.3%, respectively, for the CNS (isolated). Isolated testicular relapse was observed in 3.9% of male patients.This risk-directed therapy cured at least 50% of patients with ALL with relatively nonintensive therapy. The 80% overall survival rate for LR and AR patients at 7 years suggested that the total cure rate may be higher than 50% because of the significant salvage rate for patients who received antimetabolite-based therapy initially.

From an extended series neuroblastoma cases evaluated for MYCN amplification (MNA) at the "G. Gaslini" Hospital 15 (4 with and 11 without NMA) underwent myeloablative therapy and bone marrow transplantation (MAT-ABMT). Such cases ranged in age at diagnosis from 13 months to 7 years and were followed up at least 8 months after MAT-ABMT. MNA was present in 2/10 cases dead for disease, in 0/1 cases alive with disease, and in 2/4 cases presently in complete clinical remission. This preliminary evidence would discourage to consider MNA as a marker capable of predicting the final outcome of patients with metastatic Nb.

In the present study, 15 children with non-Hodgkin lymphoma have been immunologically evaluated by the following parameters on peripheral blood (PB) lymphocytes: phytohemagglutinin responsiveness (PHA-r); non-immune rosette formation with sheep red blood cells (RF-L) as T-cell marker; presence of surface immunoglobulins (sIg-L) as B-cell marker; serum immunoglobulins levels (IgA, IgM, IgG). Our patients (pts) have been divided in two groups: the first one includes 10 children without PB involvement; the second one includes 5 pts with bone-marrow and PB invasion. From our data it appears that: 1) the majority of pts of the first group presented normal values of membrane markers; PHA-r was impaired in 4/8 pts; 2) in pts with PB invasion absolute number of B and "null" cells was always abnormal and PHA-r altered; 3) in the second group of pts, a "null" cell origin can be suggested by the high percentage and absolute number of cells without surface markers. In our opinion, the high incidence of "null" cells represents the most relevant question: whether they are cells deprived of specific markers, or endowed with markers not identifiable by our current techniques, remains to be established.

The spleen is the least common intra-abdominal site for the development of cystic disease. A lymphoangioma of the spleen was first reported in 1885 by Fink; since that time 47 cases of lymphoangioma or lymphoangectasia have been reported. This report concern a case of cystic lymphoangioma of the spleen consisting of a large splenic cyst with associated multiple small subcapsular cysts and lymphangectasia. The diagnosis and treatment of splenic cysts are discussed and a new classification of splenic cysts is proposed.

Thirty-six children with acute lymphoblastic leukaemia (ALL) in second remission were treated with conventional chemotherapy or with cyclophosphamide and fractionated total-body irradiation followed by an allogeneic bone marrow transplant; the choice of treatment was dictated by the availability of an HLA-identical sibling. The age, sex, clinical data at presentation of the disease and duration of first remission were comparable for the two groups of patients. In the bone marrow transplantation group two patients died of graft-versus-host disease and five of leukaemia. Ten patients survive, nine disease free, 13-53 months from second remission (6-51 months post-bone marrow transplantation). In the chemotherapy group 14 patients died of leukaemia (2-29 months from second remission) and five survive (22-34 months from second remission). The actuarial survival for patients with bone marrow transplantation is 48% at 4 years as compared with 22% for those of the chemotherapy group (P = 0.04); the actuarial probabilities of being in remission are 58 and 18% in the two groups respectively (P = 0.01). This study confirms that allogeneic bone marrow transplantation is superior to chemotherapy in patients in second remission with ALL and should be considered in the presence of an HLA-identical sibling.

In 22 patients with ALL in first complete remission, who discontinued therapy after 3 years, longitudinal follow-up of immunological reconstitution was investigated by assessing serum immunoglobulin levels, number and mitogen responsiveness of B and T lymphocytes. Major modifications have been demonstrated for T cells both in terms of number and functionality, while B cells and serum immunoglobulins did not change significantly. Examining the behaviour of the patients one by one, it has been observed that recovery is often characterized by a remarkable rebound occurring from the 15th to the 18th month. Immunosuppression induced by antileukemic treatment appeared to be a transitory phenomenon, mainly limited to the first three months. Reconstitution was achieved, in almost all cases, within one year after treatment was stopped.

Peptichemio (PTC) is a mixture of six synthetic peptides of m-L-phenylalanine mustard. It acts with both alkylating and antimetabolic effects, interfering with the synthesis of DNA, RNA, and proteins. PTC was administered iv to 18 previously untreated children with advanced neuroblastoma at a dose of 1-1.5 mg/kg/day for one to three cycles of 5-6 consecutive days each. Eleven of 12 patients (92%) experienced both objective and subjective improvement; complete remission was achieved in two of them. In spite of the high remission rate, the median duration of remission has been short (4 months) and the overall survival (median, 6 months) did not seem to be influenced by the use of PTC. The primary toxic effects were, in order of importance, bone marrow depression, phlebosclerosis, nausea and vomiting, and alopecia. Chronic use of PTC seems limited by two major factors: profound long-lasting thrombocytopenia and severe phlebosclerosis.

The spleen is the least common intra-abdominal site for the development of cystic disease. A lymphangioma of the spleen was first reported in 1885 by Fink; since that time 47 cases of lymphangioma or lymphangectasia have been reported. Up to now, no CT study has been published. This report concerns a case of cystic lymphangioma of the spleen consisting of a large splenic cyst with associated multiple small subcapsular cysts and lymphangectasia. The utility of CT in diagnosis is presented.