First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

[Recurrent pneumothorax in a child with Langerhans' cell histiocytosis]. / Nawracajaca odma oplucnowa u dziecka chorego na histiocytoze z komórek Langerhansa.

We are presenting a 16 months old boy, who has been previously developing normally, physically very active, and who suddenly developed right-sided pneumothorax with infiltrations in both lungs, initially defined as inflammatory. After placing suction drainage of the pleural cavity and antibiotic administration the child's condition improved quickly. The infiltration changes still remained in lungs arousing a suspicion of fibrocystic changes. During an attempt at changing the drainage into a water one, the symptoms of pneumothorax with hypertension increased again. A minithoracotomy with an edge resection of segment 4 and pleurectomy were performed, relating to the histopathological test of the sample, Largenhans' cell histiocytosis was diagnosed. The symptoms of diabetes insipidus appeared. The treatment according to the program DAL-HX83/90 modified by the Polish Group for Leukaemia and Malignant Lymphoma was introduced. During the treatment inducing remission a pneumothorax occurred two more times.

[Deafness, as a complication of Pseudomonas aeruginosa septicemia in a 9-year old boy with acute lymphoblastic leukemia]. / Gluchota, jako powiklanie posocznicy wywolanej paleczka ropy blekitnej u 9-letniego chlopca chorujacego na ostra bialaczka limfoblastyczna.

We described natural history of Pseudomonas aeruginosa septicemia in 9 year old boy, who was treated for acute lymphoblastic leukemia (ALL). After 14 day treatment of ALL the following signs and symptoms occurred: fever, earache with otorhoea, deafness, bilateral peripheral paralysis of n. VII, erythema, pneumonia, paralytic ileus. After 4 weeks of antimicrobial and supportive therapy, in the 10th week of chemotherapy, he achieved haematological remission. During continuation therapy, two-stage bilateral myringoplasty was performed. At present the maintenance therapy is continued, and in the future hearing aid and cochlear implant, will be applied.

[Mesenteric lipoblastoma in 13-month-old boy]. / Lipoblastoma krezki u 13-miesiecznego chlopca.

A case of lipoblastoma of mesentery in 13-month-old normally growing up boy was presented. During routine examination due to upper respiratory airways viral infection large abdominal tumor was found. Preoperative diagnostics let us establish its the most probable macro- and microscopic character and the tissue limits. Radical operation was performed. During the 5-month follow up period after the surgery there were not evident complications, we did not find any signs of tumor recurrence.

[Results of treatment of children with chronic myelogenous leukaemia (CML) obtained by the Polish Paediatric Leukaemia/Lymphoma Study Group]. / Wyniki leczenia dzieci chorych na przewlekla bialaczke, szpikowa (CML) w materiale Polskiej Pediatrycznej Grupy ds Leczenia Bialaczek i Chloniaków u Dzieci.

Retrospective analysis of 102 children with CML from 9 paediatric centres in Poland has been performed. A total number of 102 children: 58 boys and 44 girls aged 1-17 years (median 9.4 years old) with CML, treated in the period 1975-1999 were included in the study. Forty eight of 102 (47.1 %) children were treated with cytostatic drugs without IFN alpha: busulfan, hydroxyurea, 6-mercaptopurine or etoposide (VP-16). Fifty four of 102 (52.9%) patients were treated with interferon alpha (IFN alpha) after cytoreductive pretreatment. Thirty out of 102 (29.4%) patients underwent stem cell transplantation (SCT): 24 - matched related donor allo-BMT, 2 - matched unrelated donor allo-BMT, 1 - partially matched related donor T-cell depleted allo-PBPCT, 1 - syngeneic allo-BMT and 2 - autologous PBPCT. Overall survival analysis revealed that 46 of the 102 (45.1%) children remained alive: 5/35 (14.3%) children treated with cytostatics alone, 22/37 (59.5%) children treated with IFN alpha and 19/30 (63.3%) children treated with SCT. Among SCT survivors there are 10/17 (58.8%) children treated with IFN alpha prior to SCT and 9/13 (69.2%) children treated with cytostatics alone prior to SCT. The probability of 5-year survival is 0.51 in the group treated with SCT (median follow-up 58 months); 0.43 in the group treated with IFN alpha (median follow-up 53 months) and 0.23 in the group treated with cytostatics (median follow-up 31 months). Our data show, that BMT is the treatment of choice in CML in children. IFN alpha could be successfully applied as an alternative treatment for those, who do not have a suitable donor for allogeneic SCT. Better outcome in post BMT children, who were not treated with IFN alpha prior to SCT requires confirmation by studies on larger groups of patients. However, it seems to be justified to stop IFN alpha therapy at least 3 months before SCT. The main reason for unsuccessful treatment outcome in patients with CML in Poland remains the still insufficient access to MUD-BMT.

[Preliminary results of BFM 96 protocol in treatment of childhood ALL relapse in the experience of the Polish Paediatric Leukaemia /Lymphoma Study Group]. / Wstepne wyniki leczenia i nawrotu ostrej bialaczki limfoblastycznej cobl wg programu BFM 96 u Dzieci w Materiale Polskiej Grupy ds. Leczenia Bialaczek i Chloniaków.

Between 1998 and 1999, 36 children aged from 3 months to 18 years (10 girls and 26 boys) with first relapse of acute lymphoblastic leukaemia were included in the study. The children were treated according to the BFM 96 relapse protocol. There were 24 cases with early (including 9 children with very early) and 12 cases with late relapse ( BM-20, local extra BM-6, combined 10). The overall second complete remission (CR) rate was 83,33%. The probability of overall EFS after 2 years was 73,3%. The results obtained with BFM 96 chemotherapy in children with first late relapse are acceptable. For children with early relapses, megachemotherapy with BMT in second remission should be used.

[Adverse reactions associated with the use of L-asparaginase during therapy of patients with nB non-Hodgkin's lymphoma. Report of the Polish Paediatric LeuKaemia/Lymphoma Study Group]. / Objawy niepozadane leczenia preparatami L-asparaginazy u chorych z nieziarniczym chloniakiem zlosliwym typu NB w oparciu o material Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków Zlosliwych u dzieci.

The aim of the study was to determine the side effects of asparaginase administration during treatment protocol for childhood non-Hodgkin's lymphoma (NHL). Drug adverse reactions occurred in 20/66 of patients (30,3%) treated in 9 centres in Poland between 1993 and 1998. The most common side effects were coagulation disturbances in 12/66 of the children (18,2%), which occurred due to reduced production of important coagulation factors. Six patients (9,1%) developed impairment of liver function (9,1%). Drug toxicity caused the modifications of treatment protocol in 12/66 (18,2%) of patients, mainly in the induction phase; 3 children died due to relapse of disease.

[Results of the treatment of myelodysplastic syndrome (MDS)obtained by the Polish Paediatric Leukaemia /Lymphoma Study Group]. / Wyniki leczenia zespolów mielodysplastycznych (MDS) uzyskane przez Polska Pediatryczna Grupe ds Leczenia Bialaczek i Chloniaków u dzieci.

Sixty children with MDS treated in six centres of the Polish Paediatric Leukaemia/Lymphoma Study Group in the period 1975-1999 were included in the study. In 20 children RAEB-T, in 13 RA, in 21 RAEB and in 6 CMML were diagnosed. Our own and literature data showed that BMT is the best therapy for children with MDS. We need a new comprehensive protocol for the diagnosis and treatment of children with MDS in Poland.

[Abdominal presentation of B-cell non-Hodgkin's lymphoma (B-NHL) - surgical treatment and its results. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group]. / Manifestacja brzuszna chloniaka B-komórkowego u dzieci - interwencja chirurgiczna i wyniki leczenia. Raport PPGLBC.

The aim of this study was to analyse the effect of LMB-89 protocol and surgical procedure at initial laparotomy on the outcome in children with abdominal B-cell NHL. The initial surgery intervention was: complete resection (20% pts), subtotal resection (20%), partial resection (4%), biopsy (36%). Postoperative complications occurred in 5 children. Complete recovery (CR) was achieved in 92% pts. There were 4% non responder patients. Two patients died before CR evaluation (tumour lysis syndrome; bleeding and multi organ failure after initial surgery). One patient died in CCR from sepsis probably influenced by the previous local operation. 10.8% patients relapsed. The estimate EFS for all patients with AB-NHL is 81%, 85% for stage III and 73% for stage IV. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival.

[G-CSF and GM-CSF in treatment of neutropaenia after chemotherapy in children with neoplasms]. / G-CSF i GM-CSF w leczeniu neutropenii po chemioterapii nowotworów u dzieci.

A total number of 608 cycles of G-CSF and/or GM-CSF was applied in 280 patients aged from 6 months to 20 years during neutropaenia associated with chemotherapy of children's neoplasms (NHL-124, NBL-42, RMS-36, Nephroblastoma-18, Osteosarcoma-17, Ewing's Sarcoma-14, Hepatoblastoma-6, Neurofibrosarcoma-6, PNET-5, Medulloblastoma-3, Fibrohistiocytoma-3, Angiosarcoma-2, other - 4). G-CSF - Neupogen (Filgastrim, Hoffman La Roche - 492 cycles) and GM-CSF - Leucomax (Molgramostim, Shering Plough - 116 cycles) were administered 5 mg/kg/day s.c. Forty one children with malignancies (NHL -21 cases, solid tumours -17) treated before cytokines were in use served as a control group. Our study demonstrated that G-CSF and GM-CSF therapy, gives a shorter period of neutropaenia, reduction of the number of febrile days, decreased frequency of infection and shortened its duration.

[A palatine tonsil as an origin site of non-Hodgkin's lymphoma: a report of two cases]. / Migdalek podniebienny jako punkt wyjscia nieziarniczego chloniaka zlosliwego--opis dwóch przypadków.

The authors describe the clinical picture of non-Hodgkin's lymphoma originated from palatine tonsil in two children: 7-year old boy and 15-year old girl. After intensive polychemotherapy the complete remission was achieved. The period after the end of treatment is now 5 months and 24 months long, respectively.

[The efficacy of BFM-90 program in the treatment of acute lymphoblastic leukemia in children in the studies of Polish pediatric leukemia/lymphoma group]. / Skutecznosc programu BFM-90 w leczeniu nawrotów ostrej bialaczki limfoblastycznej u dzieci w materiale Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków: analiza niepowodzen.

Between years 1993 and 1998, 113 children aged from 6 months to 18 years (41 girls and 72 boys) with first relapse of acute lymphoblastic leukaemia (ALL) were included in the study. All children were treated according to BFM-90 relapse protocol. Thirty-two cases were classified as very early relapses, 56 as early and 25 as late relapses. Sixty-one children had isolated bone marrow relapse, in 30 children extramedullary relapse occurred (in 21 children in central nervous system and in 16 children in testes). There were 23 combined relapses. Remission was achieved in 12 children with very early relapse (78.12%), 32 children with early relapse (85.71) and 19 children with late relapse (96%). Event-free survival in 30 months of follow-up was 29.2%, 59.0% and 73.2% for very early, early and late relapses, respectively. Sixteen children with relapsed ALL after chemotherapy according to BFM-90 relapse protocol underwent high-dose therapy with hematopoietic stem cell transplantation (in 3 cases autologous and in 13 cases allogeneic). In 6 children isolated bone marrow relapse occurred after transplantation, all of them died during subsequent chemotherapy. Ten children is alive and well from 2 to 43 months after transplantation. The results obtained with BFM-90 chemotherapy in children with first early relapses are not acceptable. Such patients require high-dose chemotherapy and transplantation of hematopoietic progenitor cells.

[The analysis of failures in the treatment of children with non-B non-Hodgkin's lymphoma. Polish pediatric leukemia/lymphoma study group report]. / Analiza niepowodzen w leczeniu dzieci z nieziarniczym chloniakiem zlosliwym typu NB. Raport Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków zlosliwych u dzieci.

The aim of the study was to evaluate the results of treatment of 46 children with non B non-Hodgkin's Lymphoma registered in 7 centers of Polish Paediatric Leukaemia/Lymphoma Study Group from 1993 to 1998. The patients were treated according to BFM-90 protocol based on German regimen. The overall probability of event-free survival for the all children after 4 years of follow-up was 71%, for patients in stage III--65%, stage IV--70%. The achieved results were not as positive as in the BFM Study Group, what was related to: the great number of children with advanced stage of disease (54.3%), the late final diagnosis, the great number of recurrences (22.5%) and deaths caused by the toxicity of medication (6.5%) (infections, drug toxicity).

[The efficacy of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of solid tumors in children. Report of Polish Pediatric Leukemia/Lymphoma Treatment Group]. / Skutecznosc G-CSF i GM-CSF w leczeniu wspomagajacym zakazen wiklajacych chemioterapie guzów litych u dzieci. Raport PPG/LBC.

Total number of 306 cycles of GM-CSF-Leucomax Sandoz (5 mg/kg/day s.c.) and/or G-CSF Filgrastim Hoffmann-La Roche (5-10 mg/kg/day s.c.) was applied in 146 children aged from 0.5-18 years during neutropenia associated with chemotherapy of solid tumours. Seventeen children with malignancies served as a historical control group. Our study have demonstrated after both G- and GM-CSF therapy shorter period of neutropenia, reduction of the number of febrile days and a decreased frequency of infectious complications and infection's duration.

[The efficacy of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of acute leukemia in children]. / Skutecznosc G-CSF i GM-CSF w leczeniu wspomagajacym zakazen wiklajacych chemioterapie ostrych bialaczek u dzieci.

Growth factors (G-CSF Neupogen Roche i GM-CSF Leucomax Sandoz) have been applied in 133 therapeutic and prophylactic cycles in 88 children with acute leukaemias. GM-CSF and G-CSF were administered subcutaneously or intravenously at a dose of 2 to 8 micrograms/kg for 2 to 28 days. 45 prophylactic cycles had been administered in children with acute lymphoblastic leukaemia in high risk group and in relapses, which caused significant reduction in the number of infections, time of neutropenia and fever. Therapeutic cytokines cycles were applied when the absolute neutrophil count have fallen below 0.5 x 109/l. We observed significant reduction in duration of neutropenia in these cycles. Tolerance of GM-CSF and G-CSF was good. Side effects were not observed.

[The effectiveness of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of non-Hodgkin's lymphoma in children. Report of Polish Pediatric Leukemia/Lymphoma Treatment Group]. / Skutecznosc G-CSF i GM-CSF w leczeniu wspomagajacym zakazen wiklajacych chemioterapie nieziarniczych chloniaków zlosliwych u dzieci. Raport PPG/LBC.

Total number of 252 cycles of GM-CSF-Leucomax Sandoz (5 mg/kg/day s.c.) and/or G-CSF Filgrastim Hoffmann-La Roche (5-10 mg/kg/day s.c.) was applied in 124 children aged from 0.5-20 years during neutropenia associated with chemotherapy of non-Hodgkin's lymphoma (NHL). Twenty four children with NHL treated according to the same chemotherapy protocol but without G-CSF and GM-CSF served as a control group. Our study have demonstrated the good efficacy of both G-CSF and GM-CSF therapy. They shortened the period of neutropenia, reduced the number of febrile days, infection's duration and decreased the frequency of infectious complications.

[Ultrasonographic evaluation of thyroid in patients cured from Hodgkin disease]. / Ocena ultrasonograficzna tarczycy pacjentów wyleczonych z choroby Hodgkina.

Long-term prognosis in patients cured from Hodgkin's disease (HD), diagnosed in childhood has dramatically improved. This is why, early detection and elimination of treatment side-effects has become essential. The study aimed at thyroid morphology evaluation in 46 patients remaining in complete remission more than five years after completion of treatment for HD. Thyroid morphology was assessed by palpation and ultrasonography. Control group consisted of 43 age- and sex-matched healthy people. 17.4% of patients after HD treatment had abnormal thyroid morphology on physical examination (gland enlargement, increased consistency or presence of nodules). Thyroid volume in this group was significantly decreased comparing to control group (p < 0.005). 32.6% of patients had heterogenic echogenicity. Ultrasonography revealed pathological lesions in 21.7% of examined individuals. Single hypoechogenic lesions in 5 patients, multiple hypoechogenic in 4 patients and multiple hypo- and hyperechogenic in 1 existed. High frequency of pathological thyroid lesions in thyroid of patients cured from HD emphasizes the need for systematic ultrasonographic thyroid evaluation.

[The osteoarthralgic symptoms preceding acute lymphoblastic leukemia]. / Objawy kostno-stawowe wyprzedzajace ujawnienie ostrej bialaczki limfoblastycznej.

Osteoarthralgia is a common symptom at the beginning of acute lymphoblastic leukaemia (ALL). It occurs in 40% of cases. Still arthritis that precedes haematological malignancies is very rare. However in every case of arthritis of unknown origin or drug resistance arthritis the bone marrow biopsy is required. We present 3 cases of osteoarthralgia that precedes ALL by 2.5-7 months.

[Acute lymphoblastic leukemia in children with Fanconi anemia]. / Ostra Bialaczka limfoblastyczna u dzieci z zespolem Fanconiego.

Fanconi anaemia (FA) is a rare autosomal recessive disorder. Manifestation of the disease is pleomorphic and may include many congenital malformations and marrow aplasia. Congenital disorders include: skeletal abnormalities, hypo- or hyperpigmentation of the skin, renal or heart anomalies and many others. FA is an invariably fatal disease owing to progressive marrow aplasia or the development of acute leukaemia or squamous cell carcinoma. We present two children with Fanconi anaemia who developed acute lymphoblastic leukaemia in the 4 and 12 year of life.

[Tumor lysis syndrome in the course of neoplastic disease of hematopoietic system in children]. / Zespól lizy guza w przebiegu chorób rozrostowych ukladu krwiotwórczego u dzieci.

Tumor lysis syndrome is characterized by hyperuricemia, hyperkalemia and hyperphosphatemia followed by hypocalcemia. Sometimes they are accompanied by hyperglycemia. It can lead to acute renal insufficiency, neurological and cardiological disorders. In the Clinic of Paediatric Haematology and Chemotherapy in Zabrze, in the period from Jan.01, 1990 to Dec.31, 1997, 305 children were treated due to neoplastic diseases of haematopoietic system: 169 with ALL, 34--ANLL, 48--NHL and 54--HD. Tumor lysis syndrome was found in 11 children, what was 3.6% of all patients. They included 3 children with ALL/1 from group SRG and 2 with HRG/, 2 with ANLL, 6 with NHL/2 with NB-NHL and 4 with B-NHL/. Tumor lysis syndrome did not occur in any patient with HD. Two symptoms of tumor lysis syndrome were found in 13 children (4.26%) including 3 with ALL (1 SRG and 2 HRG), 2 with ANLL and 8 NHL/3-NB-NHL and 5-B-NHL/. Diabetes occurred in two children with ALL. Acute renal insufficiency occurred in 6 children with ALL, 2 with ANLL and 8 with NHL. Two patients with B-NHL required dialysis. One renal insufficiency treated with hemodialyses was the first symptom of lymphoma. To prevent the consequences of tumor lysis syndrome hydration with alkalization, constant monitoring of the above mentioned biochemical parameters are necessary. Acute renal insufficiency, not responding to conservative treatment, should be immediately treated with hemodialyses and chemotherapy should be introduced under its 'shield'.