Fatal chemotherapy-induced encephalopathy following high-dose therapy for metastatic breast cancer: a case report and review of the literature

Chemotherapy-induced encephalopathies occur in a variety of clinical settings and the most detailed accounts have been described following combination methotrexate and radiation therapy. The case described herein developed severe encephalopathy following a high-dose chemotherapy protocol used in the treatment of metastatic carcinoma of the breast. Visual symptoms developed 3 weeks after completing high-dose chemotherapy and peripheral blood hematopoietic stem cell transplantation. Over the next several weeks, additional neurologic deficits developed and continued to progress despite various treatment interventions. Diffuse deep gray matter damage was identified on MR imaging and a brain biopsy revealed pathological findings similar in many respects to those described for methotrexate/radiation, cisplatin, BCNU and/or 5 FU/levamisole-related leukoencephalopathy. The patient succumbed to complications resulting from the CNS disorder, 8 weeks after the onset of symptoms. This case is unusual for two reasons. First, the patient developed severe encephalopathy following a high-dose chemotherapy protocol commonly used in the treatment of metastatic breast carcinoma and second, the encephalopathy involved primarily deep gray matter structures rather than white matter.     

Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review

Neurological complications during the treatment of hematological malignancies have a wide range of causes. Treatment-related leukoencephalopathy has been recognized as a major complication of combined chemotherapy and radiotherapy for central nervous system (CNS) lymphoma, and can complicate the diagnosis of CNS infection. Herein, we present a patient with diffuse large B-cell lymphoma who developed herpes simplex encephalitis (HSE) and subsequent cytomegalovirus encephalitis after chemoradiotherapy for CNS relapse. Although cerebrospinal fluid examination (CSF) showed no significant pleocytosis, brain magnetic resonance imaging and polymerase chain reaction analysis of the CSF were useful in the diagnosis. With a review of the literature on the association between HSE and radiotherapy for CNS malignancies, our case suggests that an awareness of viral encephalitis is important in the differential diagnosis of acute neurologic disturbance during chemoradiotherapy for CNS lymphoma.     

Intensive treatment of AIDS-related non-Hodgkin's lymphomas with the MACOP-B protocol

Abstract: The usefulness of intensive chemotherapy with the MACOP-B protocol was evaluated in 8 patients with AIDS-related non-Hodgkin's lymphoma (NHL). Four patients had a prior AIDS diagnosis. The median CD4+ lymphocyte count was 0.079 cells × 10⁹/1 (range 0.016–0.330). All patients responded to treatment. Four patients finished chemotherapy, all with complete remission, while another 3 patients deteriorated prior to finishing treatment and died. The median survival was 4 months (range 1 to 86 months). Major causes of the poor outcome were AIDS-related opportunistic infections and meningeal CNS involvement by NHL developing during or after chemotherapy. Patients with AIDS-related NHL usually do not appear to benefit from treatment with MACOP-B protocol. Advanced immunodeficiency is associated with poor tolerance to treatment and inability to finish this chemotherapy protocol. MACOP-B chemotherapy does not prevent meningeal spread of lymphoma in spite of using repeatedly systemic methotrexate crossing the blood-brain barrier. CNS prophylaxis with repeated application of intrathecal methotrexate may lower the risk of meningeal spread of lymphoma, which developed in 1 of 5 patients given CNS prophylaxis as compared to 2 of 3 patients without CNS prophylaxis.     

The risks of central nervous system relapse and leukoencephalopathy in patients receiving marrow transplants for acute leukemia

The records of 415 patients who received allogeneic marrow transplants for acute leukemia were reviewed to assess the risk of central nervous system (CNS) relapse and leukoencephalopathy after marrow transplantation. The Kaplan-Meier estimates of the probability of CNS relapse posttransplant were 13% for patients with acute lymphoblastic leukemia (ALL) and 2% for patients with acute nonlymphoblastic leukemia (ANL). Previous CNS disease was significantly correlated with an increased risk of CNS relapse in patients transplanted for ALL but not for ANL. In contrast, bone marrow involvement with leukemia at the time of transplant was associated with an increased risk of CNS relapse in patients with ANL but not in patients with ALL. Seventy-one patients with ALL did not receive posttransplant intrathecal methotrexate (IT- MTX) and 127 did. The probability of CNS relapse in these two groups was 38% and 7%, respectively (P less than .02). This protective benefit from IT-MTX was present in patients both with and without a history of CNS involvement or marrow involvement at the time of transplant. In patients with ANL, 116 patients did not receive posttransplant IT-MTX and 101 patients did, but no protection from CNS relapse was observed from IT-MTX irrespective of a patient's previous CNS history or marrow status at the time of transplant. Leukoencephalopathy was seen exclusively in patients who had received radiation and/or intrathecal chemotherapy to the CNS before preparation for marrow transplantation and posttransplant IT-MTX. In such patients the risk of leukoencephalopathy was 7%. From our data, it appears that posttransplant IT-MTX is a significant benefit for ALL patients in preventing CNS relapse after marrow transplantation. A similar benefit from posttransplant IT-MTX for ANL patients cannot be established from this study. In both groups, increasing total CNS therapy was associated with an increasing risk of leukoencephalopathy.     

Central nervous system manifestations of marginal zone B-cell lymphoma

Primary or secondary central nervous system (CNS) involvement by marginal zone B-cell lymphoma (MZBCL) is rare. A retrospective analysis of patients was done with MZBCL involving the CNS, diagnosed and treated at our institution between 2004 and 2010. We identified 10 MZBCL patients with primary (six) or secondary (four) CNS involvement. Five patients presented with primary dural lymphoma and were treated with surgical resection, whole-brain radiation, or systemic chemotherapy. Only one patient had CNS relapse 5 years later. A single patient with primary intraocular lymphoma achieved clinical remission with ocular radiotherapy and systemic chemotherapy. Four patients had ocular MZBCL within 5 years of the initial diagnosis of primary ocular adnexal MZBCL and primary splenic MZBCL. There was no evidence of local recurrence in all but one who developed systemic relapse after 3 years of follow-up. Primary or secondary CNS involvement by MZBCL display indolent clinical behavior and have a generally favorable prognosis, underlining the importance of their differentiation from aggressive lymphomas that more commonly involve the CNS.     

Combined S-1 and cisplatin preoperative chemotherapy for patients with advanced gastric cancer: report of five cases

BACKGROUND/AIMS: A high response rate with acceptable toxicities is required in the setting of neoadjuvant chemotherapy. Five cases (3 stage IV, 2 stage IIIb) of advanced gastric cancer were successfully treated by neoadjuvant chemotherapy consisting of a combination of S-1 and cisplatin. METHODOLOGY: All 5 patients were men younger than age 60, with no severe complications. S-1 was administered orally (80 mg/m2/day) twice daily for 21 consecutive days, and cisplatin (60 mg/m2) was infused over 2 hours on day 8 with hydration. This schedule was repeated every 5 weeks. After each cycle, the clinical response evaluation was performed with endoscopy, barium meal, and spiral CT scan. Surgery was carried out about 3 weeks after chemotherapy. RESULTS: All patients were responders (100%) after one or two cycles. However, there was no patient with either complete response, or down-staging. Toxicities, according to the WHO criteria, were very mild and none required treatment. Postoperatively one patient died of aspiration pneumonia unrelated to the chemotherapy. The others were discharged within 3 weeks after operation without complications. CONCLUSIONS: S-1 plus cisplatin seems safe and effective as neoadjuvant chemotherapy in advanced gastric cancer patients.     

Combined intravitreal methotrexate and immunochemotherapy followed by reduced‐dose whole‐brain radiotherapy for newly diagnosed B‐cell primary intraocular lymphoma

Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate‐based systemic induction chemotherapy and consolidation high‐dose cytarabine and reduced‐dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B‐cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment‐induced leucoencephalopathy. Seventeen patients initiated and 16 completed the protocol treatment. CNS relapse occurred in 2 patients and intraocular relapse in 3. Four‐year progression‐free survival (PFS) was 74·9% and 4‐year overall survival (OS) was 86·3%, with a median follow‐up period of 48·9 months. Of 11 patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse, and 4‐year PFS and OS was 72·7% and 88·9%, respectively. Although white matter abnormalities shown by MRI were significantly increased at 4 years after rdWBRT, only one patient developed mild cognitive impairment. The combination of intravitreal chemotherapy, prophylactic systemic chemotherapy and rdWBRT for primary IOL showed a potential to reduce CNS relapse rate and improved 4‐year PFS and OS without increase of cognitive dysfunction.     

IMPROVED TREATMENT RESULTS FOR LYMPHOBLASTIC LYMPHOMA IN ADOLESCENTS AND ADULTS USING A DOXORUBICIN-BASED (APO) PROTOCOL

A multi-drug chemotherapy (APO) protocol incorporating doxorubicin was used to treat 12 patients (median age 19 years) with lymphoblastic lymphoma. The APO protocol consisted of intensive induction and consolidation phases, prophylactic CNS treatment, and 24 months of maintenance therapy. Eleven patients had an anterior mediastinal mass, while T cell markers were found on the lymphoma cells in eight of the nine cases tested. Two patients had initial CNS involvement, with one also having bone marrow replacement. Complete remission was obtained in all patients, with no deaths due to treatment toxicity. There have been four relapses, one in the patient with initial CNS and leukemic disease, two in abdominal sites, and in the mediastinum in one patient. With a median follow-up time of 30 months from diagnosis, 67% of patients remain alive in first remission. These results indicate that the APO protocol provides a highly effective approach to the management of this high grade lymphoma in adolescents and adults.     

Modified ProMACE-MOPP hybrid regimen with moderate-dose methotrexate for patients with primary CNS lymphoma

The object of this study was to assess the estimation of 2- and 5-year overall survival and tumor response and the frequency and severity of treatment morbidity with a modified ProMACE-MOPP hybrid protocol in patients with primary CNS lymphoma (PCNSL). Thirty-two immunocompetent patients were treated with a regimen of pirarubicin, cyclophosphamide, etoposide, vincristine, and methotrexate (500 mg/m(2)) administered in 21-day cycles. Intraventricular 10 mg of methotrexate was given for eight cycles once a week. Patients received 20 Gy of whole brain radiotherapy after three cycles of chemotherapy. A single cycle of chemotherapy was repeated every 4 months for 2 years. Older patients (aged >60) received a reduced dose of chemotherapeutic agents. Eighteen patients were followed up with neuroimaging and neuropsychological assessments for evidence of CNS toxicity. Sixteen patients completed the regimen as planned. The response rate was 87.5% after the initial chemoradiotherapy. The cumulative survival and progression-free survival rates at 5 years were 56 and 31%, respectively. The median survival time was 68 months. The median progression-free survival time was 39 months. Toxicity included grade 3 or 4 leukopenia in 33% of the cycles administered. There were eight grade 3 or 4 pulmonary toxicities. There were three deaths during chemotherapy: one as a result of sepsis and two of pneumonitis. Three patients (25%) experienced delayed neurologic toxicity while on the complete regimen. Maintaining the dose of methotrexate while adding chemotherapeutic agents improved disease control and overall survival in patients with PCNSL, but early toxicity and delayed neurotoxicity are still a risk of this approach.     

Therapeutic effectiveness of ranimustine chemotherapy for elderly essential thrombocythemia*

Background: We studied the clinical effectiveness of ranimustine (MCNU) chemotherapy for essential thrombocythemia (ET). Methods: MCNU chemotherapy was carried out in 14 ET patients who were 60 years of age or older, including six men and eight women. Their ages ranged between 61 and 88 years (median age: 73 years). The patients’ mean platelet count before the treatment was 1.157 ± 0.284 × 10⁶/µL. Five of the studied patients had experienced a thrombotic episode, and one had a profuse epistaxis. Patients were treated mainly by intravenous administration of MCNU. In 12 patients, the platelet count was controlled to a level less than 500 × 10³/µL, while in two patients, it was controlled to less than 700 × 10³/µL. Results: Cerebral infarction occurred in only one patient during or after MCNU therapy. Even in the cases in which thrombosis had occurred before MCNU treatment, further thrombotic events occurred in only one case. In the patient with a profuse epistaxis, bleeding improved during treatment and normal platelet count was maintained after chemotherapy. Conclusion: It was suggested that MCNU chemotherapy may be useful for the prevention of complications in elderly ET patients.     

Early detection of meningeal localization in acute promyelocytic leukaemia patients with high presenting leucocyte count

Extramedullary relapse occurs infrequently in acute promyelocytic leukaemia (APL) but has been increasingly reported after the advent of all-trans retinoic acid (ATRA) treatment, probably as a consequence of improved patient survival. We describe our single centre experience of six APL patients who had disease localization in the central nervous system (CNS). In three patients, clinical symptoms (headache and/or nausea) that presented during follow-up led to the performance of a lumbar puncture and detection of overt CNS infiltration. Two of these patients had simultaneous haematological relapse and one was in molecular remission when CNS leukaemia was documented. One patient with no local symptoms showed CNS infiltration at the time of molecular relapse. Following the introduction of routine lumbar puncture, carried out after front-line induction in all newly diagnosed patients with white blood cell count (WBC) greater than 10 x 109/l, two additional patients in molecular remission with no local symptoms were found to have initial APL localization in the CNS. Presenting features included in 6/6 patients an elevated WBC count (> 10 x 109/l) and a predominance of the PML/RAR bcr3 type (5/6 patients) and of microgranular morphology (5/6 patients). Our findings highlight the importance of carrying out lumbar puncture in APL patients presenting with high-risk features.     

MACOP-B treatment in patients with Ki-1-positive large-cell anaplastic lymphoma

Summary Nine adult patients with Ki-1-positive largecell anaplastic lymphoma were treated with MACOP-B. Two suffered from relapsed disease and had previously received chemotherapy; a third patient had received a single dose of 100mg/m² cisplatin before initiation of MACOP-B. The stage of lymphoma was determined according to the Ann Arbor Conference criteria and was II in one, III in two and IV in six patients. All patients had constitutional symptoms. Five patients had achieved complete remission 4 weeks after termination of the protocol and there were two partial remissions. One patient died of massive pulmonary embolism during the 4th week of treatment; another patient, who had received MACOP-B as salvage therapy, died of progressive lymphoma 1 month after completion of the regimen. Maximal observed toxicities according to WHO were mucositis grade 3 (n=3) and there were three cases with thromboembolic complications, including a fatal pulmonary embolism in a young patient. However, MACOP-B appears an effective, fairly well-tolerated and feasible therapy for patients with Ki-1-positive large-cell anaplastic lymphoma.Abbreviations MACOP-B methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin, cotrimoxazole - LCAL large-cell anaplastic leukemia     

Safety and feasibility of CHOP/rituximab induction treatment followed by high-dose chemo/radiotherapy and autologous PBSC-transplantation in patients with previously untreated mantle cell or indolent B-cell-non-Hodgkin's lymphoma

Patients with no prior chemotherapy and with advanced and progressive follicular lymphoma (FCL) or mantle cell lymphoma (MCL) were enrolled into a treatment protocol combining CHOP/rituximab-CHOP therapy with subsequent consolidation high-dose therapy (HDT) to evaluate the safety and feasibility of this treatment. Overall, 15 patients were enrolled and 13 patients completed the entire treatment protocol without major toxicities or increased infectious complications. One patient withdrew consent after achieving complete remission (CR) prior to HDT. One patient was taken off study with signs of disease progression after induction treatment. All patients showed stable engraftment after HDT. Response rates appear to be favorable, indicating an additional effect of rituximab and HDT. Overall, 12 of 13 patients achieved CR/CRu and one patient partial remission. Follow-up of immune reconstitution displayed transient severe combined immunodeficiency with slow normalization of the cellular and humoral compartments without a significant increase of infectious complications. Taken together, high-dose chemotherapy can be safely given following treatment with CHOP+rituximab. Efficacy in this small cohort of patients was encouraging with sustained remissions in both FCL and MCL patients. Upfront HDT should be considered as a therapeutic option especially in young and/or high-risk patients.     

Neurological complications after stem cell transplantation in childhood.

We analyzed the incidence of neurological complications in 77 patients receiving stem cell transplantation (SCT), and 12 patients (15.8%) had the following symptoms: convulsions, intracranial hemorrhage, and leukoencephalopathy. Although statistically not significant, neurological complications were seen more frequently in patients after allogeneic transplantation, and in those with acute graft-versus-host disease (GVHD) exceeding grade II. The most significant risk factor for neurological complications was identified as unrelated donor allogenic transplantation (P = 0.016). Complications were categorized into three groups, based on time of onset and symptoms: (1) convulsions during the conditioning period, (2) intracranial hemorrhage during the period of granulocyte recovery, and (3) leukoencephalopathy at around 2 months after SCT. We propose awareness of the risks of neurological complications in each period after SCT so that immediate and effective treatment of patients can be instigated.     

Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988-1991).

In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 protocol (Reiter et al, Blood 84:3122, 1994), but cranial irradiation was restricted to patients with initial central nervous system (CNS) involvement. Patients were stratified into 3 risk groups, based on leukemia cell mass and response to initial treatment: standard-risk group (SRG), risk group (RG), and experimental group (EG). As in ALL-BFM-86, a randomized study on late intensification (protocol S) was performed in RG patients, and during the study (since October 1990), early reinduction treatment (protocol II) was introduced for SRG patients. Treatment duration for all patients was 18 months. Two hundred eighteen children entered the study: 74 SRG, 127 RG, and 17 EG patients. The overall complete remission (CR) rate was 98%. The 5-year event-free survival (EFS) for all DCLSG ALL-7 patients was 65. 3% (standard error [SE] 3.2%), which was significantly different from the 73% (SE 1%) 5-year EFS achieved in the ALL-BFM-86 study (P =.02, Z-test). However, restricting the analysis to SRG patients receiving protocol II with a total duration of treatment of 18 months, the 5-year EFS rates were 64.6% (SE 4.0%) and 67% (SE 4%), respectively, and no significant difference could be established (P =.67, Z-test). The 5-year EFS rates for SRG, RG, and EG patients were 63.5% (SE 5.6%), 66.6% (SE 4.2%), and 63.3% (SE 12.0%), respectively. SRG patients receiving protocol II fared better than patients not receiving protocol II (5-year EFS 76.7% [SE 7.7] and 54. 5% [SE 7.5], respectively). No difference in 5-year EFS was observed in RG patients randomized to receive or not to receive late intensification with protocol S. The overall CNS relapse rate at 5 years was 5.5%. The incidence rate at 5 years was 11.4% in SRG patients not receiving protocol II, whereas no CNS relapses occurred in SRG patients receiving protocol II. Six children died in first complete remission and 2 children developed a second malignancy (thyroid carcinoma and acute nonlymphoblastic leukemia). Systemic high-dose methotrexate (MTX) and intrathecal chemotherapy is a safe and effective method of CNS prophylaxis in the context of BFM-oriented treatment for all children with ALL, regardless of the risk group (with the possible exception of T-ALL patients with high white blood cell counts). The results of the DCLSG ALL-7 study confirm those of the ALL-BFM-86 study showing that early reinduction with protocol II is essential in the treatment of SRG patients and that late intensification with protocol S does not improve the prognosis for RG patients.     

A case report of childhood acute lymphoblastic leukemia with leukoencephalopathy that responded to oxygenation under hyperbaric pressure therapy]

In this report, we described a case of acute lymphoblastic leukemia with leukoencephalopathy that responded to oxygenation under hyperbaric pressure (OHP) therapy. The patient was 6 year-old female who was diagnosed as acute lymphoblastic leukemia (ALL) one year and 9 months earlier. After the first relapse of the central nervous system (CNS) leukemia, intrathecal administration of methotrexate (MTX) and skull irradiation induced CNS remission. The patient was readmitted because of second CNS relapse. After the third administration of weekly intrathecal MTX injection, apathy and finger tremor were observed. Her conscious disturbance continued for two weeks and magnetic resonance imaging (MRI) revealed abnormal findings in the white matter of her brain. Subsequently OHP therapy was commenced, and the conscious disturbance was improved gradually. One month later, neuro-disturbance resolved completely and the findings of MRI were improved. We could not find any case of leukoencephalopathy which was treated with OHP in the literature. But our case suggested that OHP therapy is valuable in patient with leukoencephalopathy in the early stage.     

Burkitt's lymphoma: single‐centre experience with modified BFM protocol

Burkitt's lymphoma is a rare aggressive lymphoma, which responds poorly to standard chemotherapy regimens used to treat high‐grade non‐Hodgkin's lymphoma (NHL). The use of intensive chemotherapy protocols using alkylating agents and intensive CNS prophylaxis has dramatically altered prognosis. We have treated eight patients with Burkitt's lymphoma with a modified BFM protocol. The dose of methotrexate was reduced from 5 g/m² to 1.5 g/m² with the aim of reducing toxicity. Seven patients received a total of six cycles of chemotherapy each and one patient received five cycles of chemotherapy. Each cycle included high‐dose methotrexate, an alkylating agent (ifosphamide or cyclophosphamide) and two triple intrathecal injections of chemotherapy. Two patients with bulky abdominal disease in addition received an autologous stem cell transplant. The regimen was well tolerated with minimal toxicity. At a median follow‐up of 16 months (range 10–28), six of the eight patients (75%) were alive and in complete remission. Two patients relapsed, one 24 months post‐BFM chemotherapy and the other 1‐month post‐autologous stem cell transplantation and 2 months post‐BFM chemotherapy.     

Prosthetic valve thrombosis in pregnancy. A single-center study of 12 cases

Pregnancy in women with mechanical prosthetic heart valves carried an increased risk of thromboembolic complications due to changes in haemostasis. Prosthetic valve thrombosis is a serious complication resulting in high mortality. Ten patients from 20 to 38 years of age had 12 thromboses of mechanical heart prostheses during pregnancy. The prosthesis was mitral in 8 cases and aortic in 4 cases. The prosthesis was a ball valve in 1 case, a tilting disc in 3 cases and bi-leaflet in 8 cases. Initial emergency treatment was surgical in 3 cases and medical in 9 cases (thrombolysis in 7 cases and simple heparin therapy in 2 cases). Secondary surgery was carried out in one patient after failure of heparin therapy. There was one death in the surgical group (4 cases, 25%) and 30% foetal mortality in the surviving women. In the thrombolysis group (7 cases), two women died (28%) after failure of treatment. Both patients had mitral valve prostheses and were in cardiogenic shock. Three women, of the other 5 thrombolysed cases, were able to complete their pregnancies and had healthy babies with no foetal mortality. No per-thrombolytic embolic complications were observed. However, there was one severe bleeding complication which was successfully managed by surgical drainage. Finally, a global success rate of 75% (9 out of 12 patients) and a mortality of 30% (3 maternal deaths in the 10 patients--all with mitral valve protheses) were observed irrespective of the therapeutic protocol used. Thrombosis is the most life-threatening complication for women with prosthetic heart valve during pregnancy. Emergency surgery for valve replacement or thrombectomy is the commonest treatment. Trombolysis is classically limited by the risk of haemorrhagic and thromboembolic complications reported in the literature. In this study, thrombolysis was effective in the 71% of cases with a low risk of haemorrhagic complications.     

Treatment-related leukoencephalopathy. A study of three cases and literature review

The etiology and pathogenesis of treatment-related leukoencephalopathy remain obscure. The evidence is substantial, however, that radiation therapy in combination with higher cerebral concentrations of certain chemotherapeutic agents such as MTX increases the likelihood of permanent damage. There is no therapy of apparent benefit for treatment-related leukoencephalopathy, but reasonable alternatives include 1) withholding chemotherapy and/or radiation, 2) administering calcium leucovorin in high doses intravenously in methotrexate-induced leukoencephalopathy (26), or 3) perfusing the subarachnoid space (2) from above through an Ommaya reservoir and out from below through a lumbar puncture needle or lumbar subarachnoid catheter. Because CT scan abnormalities and subtle mental or intellectual changes are often noted before the full-blown clinical presentation, a prospective study involving periodic CT scanning as well as formal neuropsychologic testing appears worthwhile in all patients who are to receive cranial irradiation and/or chemotherapy in the prophylaxis or active treatment of CNS disease in order to detect and perhaps even to prevent this adverse side effect of cancer therapy.     

Burkitt's lymphoma: single-centre experience with modified BFM protocol

Burkitt's lymphoma is a rare aggressive lymphoma, which responds poorly to standard chemotherapy regimens used to treat high-grade non-Hodgkin's lymphoma (NHL). The use of intensive chemotherapy protocols using alkylating agents and intensive CNS prophylaxis has dramatically altered prognosis. We have treated eight patients with Burkitt's lymphoma with a modified BFM protocol. The dose of methotrexate was reduced from 5 g/m2 to 1.5 g/m2 with the aim of reducing toxicity. Seven patients received a total of six cycles of chemotherapy each and one patient received five cycles of chemotherapy. Each cycle included high-dose methotrexate, an alkylating agent (ifosphamide or cyclophosphamide) and two triple intrathecal injections of chemotherapy. Two patients with bulky abdominal disease in addition received an autologous stem cell transplant. The regimen was well tolerated with minimal toxicity. At a median follow-up of 16 months (range 10-28), six of the eight patients (75%) were alive and in complete remission. Two patients relapsed, one 24 months post-BFM chemotherapy and the other 1-month post-autologous stem cell transplantation and 2 months post-BFM chemotherapy.