Intramedullary PNET of the spine: long-term survival after combined modality therapy and subsequent relapse

Primitive neuroectodermal tumors (PNET) originating within the spinal cord are extraordinarily rare. We report a female who presented at age 21 with diffuse involvement of the lower spinal cord. After biopsy and successful treatment with radiation and chemotherapy, she recurred 10 years later with disease in her cerebellum. She was reinduced with chemotherapy and subsequently received high-dose chemotherapy with autologous stem cell support. She is alive and free of disease 11 years after her initial presentation. This represents the longest survival ever documented for a primary spinal PNET.     

Successful treatment for advanced small cell carcinoma of the ovary

Small cell carcinoma of the ovary is a rare and aggressive malignant tumour with a poor prognosis. The authors describe two females, 12 and 13 years old, who presented with advanced stage disease. They were treated with surgical resection, multiagent chemotherapy and high-dose chemotherapy followed by autologous bone marrow transplantation. They remain free of disease more than 9.5 and 14 years since the diagnosis.     

Hepatosplenic γδ T‐cell lymphoma of two adolescents: Case report and retrospective literature review in children,adolescents, and young adults

HSTCL is a highly aggressive malignancy with a poor prognosis. Case series and accounts have reported the use of different chemotherapy regimens with diverse patient outcomes. Most long‐term survivors had undergone high‐dose chemotherapy with autologous or allogeneic HCT. We describe two pediatric patients with HSTCL who were treated with chemotherapy followed by allogeneic HCT. Both patients are alive and in complete remission 2 and 8 years after therapy. Multiagent chemotherapy followed with allogeneic HCT seems to provide patients who have chemotherapy‐sensitive disease a long‐term disease‐free survival.     

Successful treatment of a child with late-onset T-cell post-transplant lymphoproliferative disorder/lymphoma

We report a novel regimen for refractory post-transplant T-cell lymphoma (PTL). Our patient presented with non-Epstein-Barr virus (EBV) related, T-cell post-transplant lymphoproliferative disease (PTLD) 3.5 years after liver transplantation. Initially diagnosed as polyclonal PTLD, the disease progressed to a monoclonal, T-cell PTL that was refractory to several chemotherapy regimens but responded to a regimen consisting of fludarabine, cyclophosphamide, cytarabine, and alemtuzumab. Consolidation therapy included high-dose chemotherapy, autologous hematopoietic stem cell rescue, and radiation therapy. She remains in remission 2.5 years later. T-cell PTL is a rare disease with a poor prognosis; this regimen provides a novel, potentially curative approach for its treatment.     

Squamous cell carcinoma of the tongue as a second malignancy in a patient previously treated for osteosarcoma

A 15-year-old girl was diagnosed with osteosarcoma; limb salvage surgery was performed after preoperative chemotherapy. Postoperatively, adjuvant chemotherapy was given for 2 years. One year after completion of chemotherapy, the patient was readmitted for systemic recurrence. Amputation of the lower extremity and wedge resection of lung metastasis were performed followed by combination chemotherapy. Two years after cessation of chemotherapy, ulcer of the tongue was noted and cervical lymph nodes were detected by palpation. Biopsy of the lesion showed squamous cell carcinoma. The patient underwent a radical partial tongue resection and postoperative irradiation, followed by chemotherapy. Six years after treatment for the second malignancy, the patient remains well without evidence of disease. Squamous cell carcinoma of the tongue as a second malignancy after treatment of osteosarcoma is quite rare. Long-term follow-up, with particular attention to the head and neck, may be warranted in children treated for osteosarcoma.     

SQUAMOUS CELL CARCINOMA OF THE TONGUE AS A SECOND MALIGNANCY IN A PATIENT PREVIOUSLY TREATED FOR OSTEOSARCOMA

A 15-year-old girl was diagnosed with osteosarcoma; limb salvage surgery was performed after preoperative chemotherapy. Postoperatively, adjuvant chemotherapy was given for 2 years. One year after completion of chemotherapy, the patient was readmitted for systemic recurrence. Amputation of the lower extremity and wedge resection of lung metastasis were performed followed by combination chemotherapy. Two years after cessation of chemotherapy, ulcer of the tongue was noted and cervical lymph nodes were detected by palpation. Biopsy of the lesion showed squamous cell carcinoma. The patient underwent a radical partial tongue resection and postoperative irradiation, followed by chemotherapy. Six years after treatment for the second malignancy, the patient remains well without evidence of disease. Squamous cell carcinoma of the tongue as a second malignancy after treatment of osteosarcoma is quite rare. Long-term follow-up, with particular attention to the head and neck, may be warranted in children treated for osteosarcoma.     

Late recurrent metastasis in Wilms' tumour

Recurrence of Wilms' tumour after 5 years of disease-free survival is rare. We present the case of a 26-year-old man who had been diagnosed of Wilms' tumour at the age of 6 years treated by surgery, chemotherapy, and radiotherapy and who remained disease free for 8 years, after which lung metastases were detected. Second complete remission was attained with surgery and chemotherapy and 20 years after initial diagnosis he again presented with lung metastases, similarly achieving complete remission with surgery and secondline chemotherapy. The clinical and biological aspects of late metastasis in this neoplasm are discussed. © 1994 Wiley-Liss, Inc.     

MVPP chemotherapy combined with radiotherapy in the treatment of Hodgkin's disease in children.

Thirty-four children with Hodgkin's disease were treated during the years 1969--75. After radiotherapy, 7--15 cycles of MVPP were given within 24--53 months. In order to avoid chronic leukopenia, leukocyte counts were made frequently during chemotherapy, and the drug doses adjusted accordingly. A complete remission was obtained in 32 of the 34 children. Two patients died because of progressive disease. Twelve of the 32 survivors have been followed for at least 5 years, and a further 12 for at least 3 years. Three children are still on chemotherapy, whereas the remaining 29 being followed are in continued complete remission.     

Influence of different treatment modalities on the curability of childhood rhabdomyosarcoma of the head or neck

We reviewed the clinical courses of 43 patients with localized and regional rhabdomyosarcoma primary in the head or neck treated according to three sequential plans of combined-modality therapy to identify independent contributions of surgery, chemotherapy and radiotherapy to disease control, survival and development of central nervous system (CNS) involvement. In the majority of patients complete surgical resection was not feasible by vitrue of tumor location or extent of disease. Combinations of vincristine, cyclophosphamide, and dactinomycin with or without adriamycin were used simultaneously or sequentially with irradiation to induce tumor regression. Radiation doses ranged from 35 to 55 Gy. In the sequential treatment group, six of 22 patients with measurable disease had complete responses to chemotherapy. Ten of 11 partial responders and 2 of 5 non-responders to chemotherapy attained complete responses with addition of radiotherapy (82% overall CR). Simultaneous chemotherapy and irradiation induced complete responses in 4 of 9 patients. Local control of minimal residual disease was uniformly achieved with radiation dose of < 50 Gy, but similar doses were effective in only 11 of 26 patients with gross residual disease. Twenty-three percent of patients developed CNS involvement as a consequence of uncontrolled or recurrent primary tumors. Although local tumor control was achieved in 79% of patients, it could not be maintained in more than 63%. Twenty-four patients (56%) have been surviving disease-free for 2.5 to 15.5 years (median 7.5 years). We conclude that a 6-week course of chemotherapy preceding radiotherapy does not result in loss of short term disease control of unresectable primary tumor. Radiation doses < 50 Gy appear adequate for eradication of minimal residual disease but inadequate for gross disease.     

Matched unrelated umbilical cord blood transplantation for a patient with chemotherapy resistant Wilms tumor

We report a patient with chemotherapy refractory Wilms tumor who underwent an unrelated donor cord blood transplant for chemotherapy refractory disease. The preparative regimen consisted of busulfan, melphalan, and anti‐thymocyte globulin, and was well tolerated. This patient did not experience significant toxicity related to the chemotherapy regimen and did not develop any graft versus host disease from his HLA (A, B, DR) 6/6 matched cord blood transplant. Follow‐up CT scans 2 years post‐transplant have shown no evidence of disease progression, with only a few pulmonary nodules remaining, which are unchanged in size from his pre‐transplant CT scan. It is possible that high‐dose chemotherapy and stem cell transplantation can be curative in patients with tumors that are non‐responsive to conventional chemotherapy. Pediatr Blood Cancer. 2010;55:763–765. © 2010 Wiley‐Liss, Inc.     

Papillary thyroid carcinoma: Demographics,treatment, and outcome in eleven pediatric patients treated at a single institution

We describe 11 cases (8 females, 3 males) of papillary thyroid carcinoma in children treated at St. Jude Children's Research Hospital over a 33-year period, and review the literature. Ages ranged from 7–25 years (median, 16 years). Six patients had primary papillary thyroid carcinoma. Five patients had secondary papillary thyroid carcinoma after treatment of Hodgkin's disease (n = 2), acute lymphoblastic leukemia (n = 2), and neuroblastoma (n = 1) with chemotherapy and cervical radiation. The typical presentation was either cervical lymphadenopathy or a thyroid mass of short duration. Treatment consisted of thyroidectomy, cervical lymph node dissection, and postoperative thyroid hormone replacement (n = 11), parathyroid reimplantation (n = 1), ¹³¹I ablation (n = 4), external-beam irradiation (n = 1), and chemotherapy with doxorubicin (n = 1) or carboplatin and topotecan (n = 1). Nine patients are alive without evidence of disease 3.0–22.4 years from diagnosis. One patient has persistent but stable disease 17.3 years after diagnosis. One patient relapsed with metastatic lung disease 0.8 years after the initial diagnosis. He continues to do well after a brief but unsustained complete radiographic remission of disease to combination chemotherapy with carboplatin and topotecan. Our review supports excellent long-term outcome for primary or secondary papillary thyroid carcinoma in pediatric patients, although complications may require close follow-up in a multidisciplinary setting. Med. Pediatr. Oncol. 28:433–440, 1997. © 1997 Wiley-Liss, Inc.     

Testicular histology and function following long-term chemotherapy of acute leukemia in children and outcome of the patients who received testicular biopsy

Wedge biopsy of the testis was performed in 46 children who had received long-term chemotherapy for acute lymphoblastic leukemia. Occult testicular infiltration was noted in three children (6.5%). Two of three children with biopsy-proven infiltration died of systemic disease in spite of local irradiation and reinduction chemotherapy. Six of 43 children shown to be negative by testicular biopsy relapsed 11 months to 15 years later, and 3 of 6 patients died of systemic disease, but none of the cases developed testicular disease. Chemotherapy-induced gonadal damage was observed in 30 of 46 children, and tubular damage was occasionally still seen 4 years after cessation of treatment. Although gonadal damage usually depends on the cumulative dosage of cyclophosphamide, intact tubular fertility index was found in several children who had received a greater dose of cyclophosphamide intermittently. Induction and maintenance chemotherapy for acute lymphoblastic leukemia had little influence on hormonal function. Testicular biopsy at the time of cessation of chemotherapy seems to be worthwhile for the subsequent strategy of treatment, and long-term surveillance for gonadal damage of long-term survivors will be required.     

Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue

BACKGROUND: The purpose of this study is to investigate the efficacy of an intensive chemotherapy induction regimen followed by myeloablative chemotherapy and autologous hematopoietic stem cell rescue (AHSCR) in children with newly diagnosed ependymoma. PATIENTS AND METHODS: Twenty-nine children less than 10 years of age at diagnosis of ependymoma were enrolled on the "Head Start" studies. Twenty-four patients with localized disease received an induction regimen including five cycles of chemotherapy (cisplatin, vincristine, etoposide cyclophosphamide, and high dose methotrexate for patients with metastatic disease). Following induction, individuals without evidence of disease proceeded to marrow-ablative chemotherapy (thiotepa, carboplatin, and etoposide) with AHSCR. RESULTS: The estimated 5-year event free survival (EFS) and overall survival (OS) from diagnosis were 12% (+/-6%) and 38% (+/-10%), respectively. The toxic mortality amongst this group of 29 patients was 10.3%. Younger age (less than 18 months at diagnosis) was the only statistically significant prognostic factor. The estimated 5-year OS rate for the five patients with metastatic disease at presentation was 80% (+/-18%). Overall, radiation-free survival at 5 years from diagnosis was 8% (+/-5%). CONCLUSIONS: The use of an intensive induction chemotherapy regimen including myeloablative chemotherapy followed by AHSCR in newly diagnosed young children with ependymoma is not superior to other previously reported chemotherapeutic strategies.     

MVPP CHEMOTHERAPY COMBINED WITH RADIOTHERAPY IN THE TREATMENT OF HODGKIN'S DISEASE IN CHILDREN

ABSTRACT. Thirty-four children with Hodgkin's disease were treated during the years 1969–75. After radiotherapy, 7–15 cycles of MVPP were given within 24–53 months. In order to avoid chronic leukopenia, leukocyte counts were made frequently during chemotherapy, and the drug doses adjusted accordingly. A complete remission was obtained in 32 of the 34 children. Two patients died because of progressive disease. Twelve of the 32 survivors have been followed for at least 5 years, and a further 12 for at least 3 years. Three children are still on chemotherapy, whereas the remaining 29 being followed are in continued complete remission.     

Hodgkin's disease in children

From 1921 to 1973, 106 children with Hodgkin's disease under the age of 17 years were seen at Roswell Park Memorial Institute and were analyzed retrospectively. Evaluation was separated into three eras: 1921–1949 (early era), 1950–1964 (middle era), and 1965–1973 (recent era). In the early era, suboptimal radiation therapy was employed. In the middle era, radiation therapy techniques were improved, and single-agent chemotherapy was introduced. In the recent era, multiagent chemotherapy routines were frequently used; aggressive external megavoltage radiation therapy became routine in conjunction with improvement in staging procedures. The best survival was observed in the recent era where five-year survival of 96% was noted in early stage disease. Favorable prognostic features included: younger age group (5–9 years), female sex, lymphocytic predominant histology, early stage disease, and complete response to therapy. Nodular sclerosing and mixed cell types had an equal prognosis. The concept of involved area radiotherapy along with combination chemotherapy appears a reasonable approach in children and should be tested in a randomized study against more extensive radiotherapy techniques in early stage disease.     

Covert bacteriuria in schoolgirls in Newcastle upon Tyne: A 5-year follow-up?

Two hundred and fifty-two schoolgirls with covert bacteriuria were followed up for 5 years. Forty-one girls were prescribed obligatory chemotherapy because of renal involvement, mainly scarring. Of the remaining 211 girls, 106 were randomly allocated to a no chemotherapy group and 105 to a chemotherapy group to receive a 2-year course of chemotherapy. Treatment was highly effective with 98% showing some response bacteriologically and 90% being culture-negative at 2 years. However, at 5 years—that is 3 years after stopping treatment—this had fallen to 64%. In the no chemotherapy group 40% had spontaneously become culture-negative at 2 years and this had increased to 49% at 5 years. The difference at 5 years between the two groups attains statistical significance. During follow-up, 11% of the no chemotherapy group and 9·5% of the chemotherapy group developed symptomatic disease of the urinary tract. Renal growth was measured by calculating regression lines for the relationship between kidney length and the distance between the 1st and 3rd lumbar vertebrae. The rate of growth of the kidneys over 5 years in the two randomised groups was similar. Only one girl (no chemotherapy group) developed a new renal scar during the study. Measurement of the growth rate of individual kidneys in the obligatory chemotherapy group showed that, despite chemotherapy, there was below average growth in 21 out of 33 scarred kidneys and in 8 patients the degree of renal scarring had increased. It was concluded that, when kidneys were radiologically normal, covert bacteriuria did not lead to renal damage or impaired renal growth in the subsequent 5 years, even if it remained untreated. Consequently, it is recommended that schoolchildren should not be screened for covert bacteriuria until a non-radiological method can be devised to detect those with renal scarring.     

Chemotherapy and irradiation in childhood Hodgkin's disease.

Eighty children aged less than 16 years with newly diagnosed Hodgkin''s disease were treated between 1974 and 1982. Complete remission occurred in 95%, with actuarial five year overall survival of 94%, and relapse free survival of 82%: median follow up was 4.8 years. Sixty one children were staged clinically while 19 had staging laparotomies before treatment. Most received combined modality treatment with Ch1VPP chemotherapy (chlorambucil, vinblastine, procarbazine, and prednisolone) followed by irradiation of initial bulk disease. Nodular sclerosis predominated in both sexes, accounting for 60% of the total. Girls with stage IV disease, nodal sclerosis histology, and bulky mediastinal masses had a relatively poor prognosis. Ten children have relapsed, and three prolonged (6 to 7 years) second remissions have been observed. Four died of disease, and one from infection. Clinical staging, avoiding splenectomy, reduced the risk of serious infections. Our current policy is to treat stage IA disease with local irradiation and all other stages with chemotherapy, adding irradiation for bulky mediastinal disease.     

Prognostic Criteria, Treatment and Survival in Disseminated Histiocytosis X

Toogood, I. R. G., Ellis, W. M., and Ekert, H. (1979) Aust. Paediatr. J. , 15, 91–95. Prognostic criteria, treatment and survival in disseminated histiocytosis X. Twenty-five children with disseminated histiocytosis X, diagnosed between 1969–75, were clinically grouped into those without organ dysfunction (Group I) and those with organ dysfunction (Group II). They were treated with either oral chlorambucil (CBL) or combination chemotherapy with vinblastine and other agents. Children less than three years of age at the commencement of treatment had Group II disease more frequently (p = 0.02), and children with Group I disease had significantly longer survival (p = 0.04). Oral histiocytosis X was present in 10 children and is frequently associated with diabetes insipidus (p<0.001). Initial response to chemotherapy did not predict prognosis (p = 0.38). Treatment with CBL alone was effective in all children with Group I disease over the age of three years at the onset of symptoms. However, combination chemotherapy appeared to be necessary in children with Group II disease from the time of diagnosis. and in children with Group I disease whose symptoms occur before the age of three years. Chemotherapy is associated with minimal toxicity and has resulted in a survival rate of 80% with a 37-month median follow-up of survivors (range 2–118 months).     

Combination chemotherapy in osteogenic sarcoma: the Memorial Sloan-Kettering cancer center experience (author's transl)

In 61 patients (pts.) with biopsy proven osteogenic sarcoma a disease free survival rate of > 80% was obtained using T-7 chemotherapy. This can be explained by successful eradication of pulmonary micrometastases with aggressive chemotherapy. The prognosis for pts. < 12 years was significantly improved since a higher dose off Methotrexate was used for this younger age group. The histologic effect of preoperative chemotherapy on the primary tumor is of prognostic value for the outcome of the disease. Pts. with good histologic effect on the primary tumor (grade III and IV effect) show a 100% disease free survival rate, whereas pts. with poor histologic effect (grade I and II effect) have a 50% chance to develop metastases. The role of cis platinum in future therapeutic trials is discussed based on the experience with cis platinum in phase II trials.