Autologous stem cell transplantation followed by consolidation chemotherapy for relapsed or refractory Hodgkin's lymphoma

Relapse remains a major cause of treatment failure after autotransplantation (auto-PBSCT) for Hodgkin's disease (HD). The administration of non-crossresistant therapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after auto-PBSCT in 37 patients with relapsed or refractory HD. Patients received high-dose gemcitabine-BCNU-melphalan and auto-PBSCT followed by involved-field radiation and up to four cycles of the DCEP-G regimen, which consisted of dexamethasone, cyclophosphamide, etoposide, cisplatin, gemcitabine given at 3 and 9 months post transplant alternating with a second regimen (DPP) of dexamethasone, cisplatin, paclitaxel at 6 and 12 months post transplant. The probabilities of event-free survival (EFS) and overall survival (OS) at 2.5 years were 59% (95% CI=42-76%) and 86% (95% CI=71-99%), respectively. In all, 17 patients received 54 courses of CC and 15 were surviving event free (2.5 years, EFS=87%). There were no treatment-related deaths during or after the CC phase. Post-transplant CC is feasible and well tolerated. The impact of this approach on EFS should be evaluated in a larger, randomized study.     

Cases of chemotherapy and/or radiotherapy for esophageal carcinoma followed by esophagectomy because of tumor progression

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Cases of chemotherapy and/or radiotherapy for esophageal carcinoma followed by esophagectomy because of tumor progression     

BVAC ablative chemotherapy followed by autologous bone marrow transplantation for patients with advanced lymphoma

Forty-one consecutive patients with lymphoma resistant to conventional combination chemotherapy have been entered into a study in which chemo-ablative therapy and autologous marrow rescue were used with curative intent. The actuarial proportion of 20 patients with Hodgkin's lymphoma remaining alive and free of recurrent disease is 49%, while that for 21 patients with non-Hodgkin's lymphoma is 41%. Our clinical approach to these patients involved a strategy whereby lymphomatous nodes greater than 2 cm in diameter that persisted despite salvage chemotherapy were given boost radiation therapy immediately before chemo-ablation. However, patients with this variable had a significantly lower survival due to septic complications rather than recurrent disease. We conclude that the treatment strategy used in this study with some modification may improve further on the already high probability of long-term disease-free survival experienced by this group of patients.     

Eight-drug combination chemotherapy (MOPP and ABDV) and local radiotherapy for advanced Hodgkin's Disease.

Thirty-seven patients with advanced Hodgkin's disease have been treated for greater than or equal to 3 months with a protocol consisting of alternate monthly courses of MOPP (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone) and ABDV (adriamycin, bleomycin, DTIC, and vinblastine) with local radiotherapy (RT) to areas of originally bulky disease. This therapy produced CR in 19 of 19 previously untreated patients (100%), eight of nine previously treated with RT (89%), and six of nine previously treated with RT and MOPP (67%). The remaining patients are all PRs tending toward CR status. The median time to CR was 3.0 months. The median time in remission to date for the previously untreated patients is 8+ months (2+-14+). After an induction period of eight cycles of chemotherapy patients are maintained on alternate-month treatment continuing the alternating sequence. During this phase three patients have experienced reappearance of disease (one recurrence, one possible second primary lymphoma, and one recurrence in a patient whose original diagnosis is in doubt). The regimen has been well tolerated. All patients were treated as outpatients. Alopecia and neurotoxicity were mild and myelosuppression was moderate. Clinically significant cardiopulmonary toxicity has been limited to mild radiation pneumonitis in one patient and bleomycin pneumonitis which cleared during prednisone in a second patient.     

ChlVPP/ABVVP, a first line 'hybrid' combination chemotherapy for advanced Hodgkin's lymphoma: a retrospective analysis

We retrospectively analysed toxicities and clinical results of 61 Hodgkin's lymphoma patients treated with chlorambucil, vinblastine, procarbazine, doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a weekly alternate schedule. Of 61 patients, 33 were in stages III-IV, 21 in stage IIB and seven in stage IIA with bulky disease or extranodal presentation. ChlVPP/ABVVP was administered for 6-8 cycles. Involved field radiotherapy (IFRT) (30-35 Gy) was delivered to 31 patients with residual disease after chemotherapy or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete clinical or radiological remission after chemotherapy and IFRT. With a median follow-up of 60 months, 5-year overall survival, relapse- and event-free survival were 78.8% (95% CI 68.2-91.1%), 81% (95% CI 70.6-92.2%) and 71.9% (95% CI 68.2-82.2%) respectively. Grades 3-4 neutropenia was the most relevant haematological toxicity and occurred in 82% of patients. Non-haematological toxicities were mild and reversible. No toxic deaths were recorded. One patient developed secondary acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective nature of this study, no definitive conclusions could be drawn about the clinical activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone), MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), with a lower degree of haematological and non-haematological toxicity. Long-term results of the ongoing randomized trial, comparing ABVD versus high-dose intensity weekly regimens will be useful to confirm our results.     

Treatment of post-transplant lymphoproliferative disease with induction chemotherapy followed by haploidentical peripheral blood stem cell transplantation and Rituximab

Management of monoclonal lymphoproliferative disease following stem cell transplantation is difficult and previous attempts to eradicate tumor using chemotherapy or radiation therapy alone have not been successful. We report successful early eradication of an EBV negative, B cell non-Hodgkin's lymphoma in a child who received a T cell-depleted, maternal haploidentical bone marrow transplant for severe combined immunodeficiency disease. Our treatment strategy involved combining conventional induction chemotherapy with re-transplantation using the paternal donor as a source of peripheral blood stem cells, followed by treatment with anti-CD 20 monoclonal antibody (Rituximab). This strategy exploits the potential graft-versus-tumor activity of the mature T cells in the graft, while providing a source of stem cells to confer long-term immune function. The administration of Rituximab in the early post-transplant course may provide additional anti-tumor activity without affecting the new stem cell compartment.     

Thyroid functions in long-term survivors of pediatric Hodgkin's lymphoma treated with chemotherapy and radiotherapy

Objective: Post-treatment endocrine disturbances are common in cancer patients who have received radiotherapy or chemotherapy. The objective of this study was to evaluate the thyroid functions of long-term survivors of pediatric Hodgkin’s lymphoma treated with chemotherapy and radiotherapy.Methods: Thyroid functions of 55 Hodgkin’s lymphoma patients (M/F:2.05/1) in complete remission were evaluated retrospectively.Results: The mean age of the patients at diagnosis was 10.35±4.09 (range: 2.83-17) years and the mean follow-up period was 5.54±3.68 (range: 0.92-13.92) years. All patients received chemotherapy; a total of 50 patients (90.9%) underwent radiotherapy, 42 (76.4%) of whom received neck/mantle radiotherapy. Thyroid function tests were abnormal in 14 (24.5%) patients and normal - in the remaining 41 (74.5%). A diagnosis of subclinical and overt hypothyroidism was made in 11 (78.6%) and 3 (21.4%) patients with abnormal thyroid function tests, respectively. Nearly one-fourth (21.4%) of all thyroid function disorders were detected in the first year of follow-up. A statistically significant correlation was found between the dose of mantle radiotherapy and thyroid function disorder (p=0.002). In addition, statistically significant correlations were established between thyroid examination or thyroid ultrasonography findings and thyroid functions (p <0.001 or p=0.006, respectively).Conclusions: Radiation-induced thyroid disorders may develop in pediatric Hodgkin’s lymphoma patients in complete remission starting as early as the first year after treatment and are dose-dependent. Patients, particularly those who have been exposed to radiotherapy of the neck, must be followed up closely for occurrence of thyroid dysfunctions.Conflict of interest:None declared.     

Ophthalmologic outcomes after chemotherapy and/or radiotherapy in non-conjunctival ocular adnexal MALT lymphoma

In the present study, we evaluated the ophthalmologic outcomes of 24 patients who received chemotherapy and/or radiotherapy for the treatment of non-conjunctival ocular adnexal mucosa-associated lymphoid tissue-type (MALT) lymphoma. Ophthalmologic outcomes were assessed in patients who received chemotherapy and/or radiotherapy from March 2004 until May 2010. Outcomes were determined according to common symptoms following chemotherapy and/or radiotherapy, which consisted of decreased visual acuity, dry eye symptoms, retinopathy, optic neuropathy, increased intraocular pressure, and blepharitis. Nine patients received chemotherapy alone, eight patients received radiotherapy alone, and seven patients received chemotherapy with additional radiotherapy (chemoradiation therapy). Patients treated by chemotherapy alone showed better ophthalmologic outcome scores (mean score, 1.56) than those treated by radiation alone or chemoradiation therapy (mean score, 4.01). In conclusion, the treatment of ocular adnexal lymphoma including radiotherapy showed poor ophthalmologic outcomes due to radiation-induced complications. Recently, many new treatment options have emerged, such as immunotherapy or radioimmunotherapy. In the future study, to select a better treatment modality with fewer complications, well-designed prospective trials with ophthalmologic outcomes are needed.     

Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1-19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27-42) and 29% (95% CI 22-36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.     

Autologous stem cell transplantation followed by consolidation chemotherapy for patients with multiple myeloma

Although high-dose therapy and autologous stem cell transplant (ASCT) is superior to conventional chemotherapy for treatment of myeloma, most patients relapse and the time to relapse depends upon the initial prognostic factors. The administration of non-cross-resistant chemotherapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after single autologous peripheral blood stem cell transplant (auto-PBSCT) in 103 mostly newly diagnosed myeloma patients (67 patients were < or =6 months from the initial treatment). Patients received conditioning with BCNU, melphalan+/-gemcitabine and auto-PBSCT followed by two cycles of the DCEP+/-G regimen (dexamethasone, cyclophosphamide, etoposide, cisplatin+/-gemcitabine) at 3 and 9 months post-transplant and alternating with two cycles of DPP regimen (dexamethasone, cisplatin, paclitaxel) at 6 and 12 months post-transplant. With a median follow-up of 61.2 months, the median event-free survival (EFS) and overall survival (OS) are 26 and 54.1 months, respectively. The 5-year EFS and OS are 23.1 and 42.5%, respectively. Overall, 51 (49.5%) patients finished all CC, suggesting that a major limitation of this approach is an inability to deliver all planned treatments. In order to improve results following autotransplantation, novel agents or immunologic approaches should be studied in the post-transplant setting.     

Bilateral radiation therapy followed by methotrexate-based chemotherapy for primary vitreoretinal lymphoma

Primary vitreoretinal lymphoma (PVRL) is a subset of primary CNS lymphoma that presents as isolated ocular disease without brain involvement. Although ocular radiotherapy (RT) is an effective treatment for PVRL, the optimal treatment is uncertain. PVRL may later involve the brain in 56%-85% of patients. We report on 12 PVRL patients treated with a combination of bilateral RT and a systemic chemotherapy (CT) regimen containing high-dose methotrexate (M). Ten received RT (30-40 Gy) followed by CT, one received RT, and one was treated with intravitreal M; all achieved a complete response (CR). Three patients had tumor recurrence in the brain and received CT and one patient relapsed in the eye with a second recurrence in the brain. Three patients achieved CR-2 remain alive and one died of dementia. One died from recurrent CNS disease. With a median follow of 68 months (range, 17-154 months), median progression-free and overall survival have not been reached. Bilateral RT followed by M-based CT is an effective treatment for reducing CNS progression and prolonging survival.