Autologous bone marrow transplantation in hematologic malignancies

Autologous bone marrow transplantation (BMT) has become effective therapy for high-risk hematologic leukemias with long-term disease-free survivals and apparent cure in a substantial fraction of patients with relapsed aggressive non-Hodgkin's lymphoma, relapsed Hodgkin's disease, and the acute leukemias. Preliminary reports suggest autologous BMT may also be useful treatment for low-grade non-Hodgkin's lymphomas, chronic myelogenous leukemia, and multiple myeloma. Recent studies have begun to address the role autologous BMT should play in these diseases, especially relative to conventional-dose therapy and allogeneic BMT. Relapse remains the major cause for failure following autologous BMT. Novel approaches that can increase the antitumor effect of this treatment without increasing toxicity are being investigated.     

Digestive complaints in patients with hematologic malignancies undergoing bone marrow transplantation

The aim of this study was to assess the severity and frequency of complaints affecting the digestive system in 57 patients with hematological malignancies, who underwent allogeneic (Group I, n = 22) and autologous (Group II, n = 35) hematopoietic stem cell transplantation. Chemotherapy-related toxicities affecting the digestive system (mucositis, nausea/vomiting, diarrhea) were assessed according to the WHO scale for organ toxicity. Selection of the feeding route (oral or parenteral) depended on the tolerance to oral nutrition. Parenteral nutrition (PN) was introduced when oral intake represented ≤ 50% of the total energy requirement over 2 days. PN was started in the third 24-h period. 63.6% of patients undergoing allogeneic transplantation and 54.3% of patients undergoing autologous transplantation needed PN. Ailments affecting the digestive system began in both groups during the administration of conditioning chemotherapy and gradually decreased in the posttransplantation period. Mucositis grade 3/4 requiring PN was observed in 85% patients in Group I and 52.7% patients in Group II. In Group I, grade 3 diarrhea was observed only in patients requiring PN. Severe grade 3/4 organ toxicity from chemotherapy was the main indication for PN in patients undergoing hematopoietic stem cell transplantation.     

Bone marrow transplantation in hemopoietic malignancies

Several developments have improved disease-free survival after allogeneic bone marrow transplantation. They have mainly involved prophylactic and therapeutic interventions to reduce some of the transplant-related complications. It is now apparent that disease control is achieved by several mechanisms, including the preparative regimen as well as immunologic interactions between tumor cells and cells that are graft derived and belong to the immune surveillance system. Appropriate manipulations of the latter group of mechanisms may result in a better understanding of disease control and make the underlying therapeutic principle universally applicable. Chronic myeloid leukemia patients in the chronic phase appear to have the most optimal risk-to-benefit ratio of all patients transplanted for hemopoietic malignancies. More recent results in acute myeloid leukemia patients transplanted in first remission, however, suggested that allogeneic bone marrow transplantation might also be acknowledged as the treatment of choice in this disease. This conclusion cannot be drawn as yet for patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and malignant lymphoma.     

Intensive cytoreductive therapy followed by autologous bone marrow transplantation for patients with hematologic malignancies or solid tumors

Fifty patients were studied. Twenty patients with non-Hodgkin's lymphomas (NHL) of high-grade malignancy and 21 patients with acute leukemia (AL) were treated with high-dose cyclophosphamide and total body irradiation, and three patients with Hodgkin's disease (HD) and six patients with solid tumors were treated with high-dose cyclophosphamide and VP16-213. Those procedures were followed by autologous bone marrow transplantation (ABMT). All patients had received conventional chemo(radio)therapy before the ABMT procedure. Although remissions were obtained in patients with cytotoxic drug-resistant diseases (lymphomas and solid tumors), none has become a long-term survivor, as occurred also in patients with solid tumors in partial remission (PR). Two of five patients with NHL in PR at the time of ABMT have become long-term disease-free survivors (28+, 56+ months). Ten patients with NHL were treated in complete remission (CR) and seven are in unmaintained CR; four with long follow-up (14+ to 59+ months). All patients with AL were treated in CR; two patients received ABMT in second CR, and both relapsed. Ten of nineteen patients in first CR relapsed; eight are alive in CR, five with long follow-up. Four deaths were therapy-related, all were patients in poor clinical condition. Intensive cytoreductive therapy followed by ABMT can produce prolonged disease-free survival (and probably cure) in a fair number of patients with poor risk NHL in CR and PR and probably also in patients with acute myeloblastic leukemia in first CR. This procedure was not successful in achieving long-term disease-free survival in patients with refractory lymphomas or solid tumors.     

Bone marrow transplantation using unrelated donors for haematological malignancies

Bone marrow transplantation from unrelated donors is increasingly used to treat haematological malignancies. There are almost 4 million volunteer donors now available. Therefore, it is possible to find an HLA-A, -B and -DR-identical donor for around 70% of the patients. The major obstacles to unrelated bone marrow transplantations have been rejection, severe acute graft-versus-host disease (GVHD) and prolonged immune recovery leading to frequent infections and a high transplant-related mortality. However, with improved tissue typing using DNA techniques, immunosuppression using T-cell depletionin vitro orin vivo, the frequency of acute GVHD is acceptable and the results approach those obtained with HLA-identical siblings. For patients with chronic myeloid leukaemia, the worldwide 3-year survival is around 40%. Other indications for bone marrow transplantation with unrelated marrow include acute leukaemia and myelodysplastic syndromes with high-risk features. Unrelated cord blood cells and unrelated peripheral blood progenitor cells will be increasingly used as alternative haematopoietic stem cell sources to bone marrow. Improved immunosuppression, more accurate tissue typing, growth factors and better management of infections is expected to improve outcome using unrelated haematopoietic stem cells for transplantation in the near future.     

Bone marrow transplantation in cancer patients

Bone marrow transplantation (BMT) has been done as one mode of cancer therapy which has the possibility of curing some cancer patients. In Nagoya, more than half of leukemia patients who received allogeneic BMT in a remission state became long-term survivors, and autologous BMT for acute lymphoblastic leukemia has been successfully done using monoclonal antibodies for purging leukemia cells from bone marrow. According to our experiences with leukemia BMT, the following essential conditions for performing successful BMT in cancer patients were discussed, 1) preconditioning therapy for eradication of cancer cells, 2) supportive care for prevention of side effects of BMT including virus infections such as cytomegalovirus, and 3) compatibility of HLA antigens.     

Recursive partitioning analysis of prognostic factors for glioblastoma patients aged 70 years or older

BACKGROUND:

The most‐used prognostic scheme for malignant gliomas included only patients aged 18 to 70 years. The purpose of this study was to develop a prognostic model for patients ≥70 years of age with newly diagnosed glioblastoma.

METHODS:

A total of 437 patients ≥70 years of age with newly diagnosed glioblastoma, pooled from 2 tertiary academic institutions, was identified for recursive partitioning analysis (RPA). The resulting prognostic model, based on the final pruned RPA tree, was validated using 265 glioblastoma patients ≥70 years of age from a data set independently compiled by a French consortium.

RESULTS:

RPA produced 9 terminal nodes, which were pruned to 4 prognostic subgroups with markedly different median survivals: subgroup I = patients <75.5 years of age who underwent surgical resection (9.3 months); subgroup II = patients ≥75.5 years of age who underwent surgical resection (6.4 months); subgroup III = patients with Karnofsky performance status of 70 to 100 who underwent biopsy only (4.6 months); and subgroup IV = patients with Karnofsky performance status <70 who underwent biopsy only (2.3 months). Application of this prognostic model to the French cohort also resulted in significantly different (P < .0001) median survivals for subgroups I (8.5 months), II (7.7 months), III (4.3 months), and IV (3.1 months).

CONCLUSIONS:

This model divides elderly glioblastoma patients into prognostic subgroups that can be easily implemented in both the patient care and the clinical trial settings. This purely clinical prognostic model serves as a backbone for the future incorporation of the increasing number of potential molecular prognostic markers. Cancer 2012. © 2012 American Cancer Society.     

Concurrent chemoradiotherapy for limited-disease small cell lung cancer in elderly patients aged 75 years or older

Background: The optimal treatment for limited-disease small cell lung cancer(LD-SCLC) in patients aged 75 years or older remains unknown. Methods: Elderly patients with LD-SCLC who were treated with chemoradiotherapywere retrospectively reviewed to evaluate their demographiccharacteristics and the treatment delivery, drug toxicitiesand antitumor efficacy. Results: Of the 94 LD-SCLC patients treated with chemotherapy and thoracicradiotherapy at the National Cancer Center Hospital between1998 and 2003, seven (7.4%) were 75 years of age or older. Allof the seven patients were in good general condition, with aperformance status of 0 or 1. Five and two patients were treatedwith early and late concurrent chemoradiotherapy, respectively.While the four cycles of chemotherapy could be completed inonly four patients, the full dose of radiotherapy was completedin all of the patients. Grade 4 neutropenia and thrombocytopeniawere noted in seven and three patients, respectively. Granulocyte-colonystimulating factor support was used in five patients, red bloodcell transfusion was administered in two patients and platelettransfusion was administered in one patient. Grade 3 or moresevere esophagitis, pneumonitis and neutropenic fever developedin one, two and three patients, respectively, and one patientdied of radiation pneumonitis. Complete response was achievedin six patients and partial response in one patient. The mediansurvival time was 24.7 months, with three disease-free survivorsfor more than 5 years. Conclusion: Concurrent chemoradiotherapy promises to provide long-term benefitwith acceptable toxicity for selected patients of LD-SCLC aged75 years or older.     

Non-myeloablative hematopoietic cell transplantation as immunotherapy for hematologic malignancies

Conventional approaches to hematopoietic stem cell transplantation (HSCT) carry risks of morbidity and mortality from regimen-related toxicities, which have restricted the procedure to relatively young patients in good medical condition. This age restriction is unfortunate because the median age of patients with most candidate diseases (e.g., acute and chronic leukemias, myelodysplasia, myeloproliferative diseases, myeloma, and non-Hodgkin lymphoma) for HSCT is greater than 60 years. In non-myeloablative allogeneic HSCT, high-dose cytotoxic therapy as the conceptual basis for treating hematopoietic malignancies has been replaced by graft-versus-tumor effects. The use of potent pre- and postgrafting immunosuppression derived from preclinical studies has allowed omission of myeloablative cytotoxic therapy without compromising hematopoietic donor cell engraftment. This results in a marked reduction in transplant-related toxicities which makes older or medically infirm patients candidates for this treatment option. Initial results in patients with a variety of hematologic malignancies have been encouraging, with documented sustained cytogenetic and molecular remissions in a substantial number of sometimes heavily pretreated and previously refractory patients. While patients with hematologic malignancies will likely require conversion to full donor hematopoiesis for long-term disease control, a state of mixed donor/host hematopoietic chimerism might suffice to 'cure' the disease phenotypes in various non-malignant diseases. Strategies aimed at inducing donor-specific tolerance and optimizing post-transplant immunosuppression may eventually eliminate the need for pre-transplant total body irradiation which is relevant for minimizing late toxicities.     

Renal insufficiency in patients with hematologic malignancies undergoing total body irradiation and bone marrow transplantation: a prospective assessment

PURPOSE: Patients with malignant hematologic disorders undergoing bone marrow transplantation (BMT) may develop renal insufficiency. A study was undertaken to assess prospectively the subclinical renal function changes with radioisotopic methods in patients undergoing BMT for hematologic malignancies. METHODS AND MATERIALS: We studied 71 patients with normal renal function undergoing BMT for various hematologic malignancies, mostly leukemias. Conditioning included chemotherapy and 12 Gy (45 patients) or 13.5 Gy (26 patients) fractionated total-body irradiation (TBI). In 21 patients receiving 12 Gy TBI, the kidney dose was limited to 10 Gy using partial transmission blocks fabricated after renal opacification with nonionic, hypo-osmolar contrast medium. The glomerular filtration rate (GFR) and effective renal plasmatic flow (ERPF) were determined radioisotopically before conditioning and at 4, 12, and 18 months, using (51)Cr ethylene-diamine-tetra-acetic acid and (131)I ortho-iodo-hippurate, respectively. Renal insufficiency was defined as a decrease of >/=30% in GFR or ERPF compared with the baseline values. The potential influence of patient- and treatment-related variables on renal dysfunction was assessed. RESULTS: At 4 (early) and 12-18 (late) months, a >/=30% GFR drop was observed in 54% and 49% of patients and a >/=30% ERPF drop in 44% and 34% of patients, respectively. After stepwise logistic analysis, a GFR reduction at 4 months correlated significantly with age (<40 years old, worse), TBI using kidney blocks (partial kidney shielding to 10 Gy was associated with a higher rate of renal dysfunction at 4 months compared with the full TBI dose), and days of aminoglycoside/vancomycin use. An ERPF drop at 4 months was independently related with the days of amphotericin use and days of prostaglandin E(1) use (prophylaxis against hepatic venoocclusive disease). A GFR and ERPF reduction at 12-18 months correlated with days of amphotericin use and days of prostaglandin E(1) use, respectively. CONCLUSION: Early post-BMT renal dysfunction is associated with the administration of potentially nephrotoxic drugs. An inverse correlation with the prescribed TBI dose was observed; patients whose kidneys received 10 Gy through the use of partial shielding blocks had significantly greater renal dysfunction at 4 months. The administration of potentially nephrotoxic contrast agents used in radiotherapy treatment planning may be responsible for the latter observation. Prostaglandin E(1) use correlated with a significant reduction in ERPF at both 4 and 12-18 months.     

Bone marrow transplantation

One hundred seventy-one of cases bone marrow transplantation (BMT), including 132 allogeneic, 16 syngeneic and 23 autologous, were recorded in Japan during the period from September 1975 through March 1984. The number of BMT cases increase showed a rapid chronological i.e., 16 cases in 1980, 27 in 1981, 39 in 1982 and 57 in 1983. All cases were treated in clean rooms, and many of them received intensive gut decontamination using Vancomycin.     

Bone marrow transplantation from programmed donor,five years on

Certain peculiarities of a bone marrow transplantation (BMT), between two minor siblings are reconsidered; the recipient a 6.5 year old girl with an adult-type chronic myeloid leukemia, was an only child, and her parents programmed a second pregnancy hoping that the future brother (sister) could be a compatible donor for BMT. Five years after this unusual and successful BMT, the psychological profiles of the recipient, the donor and their parents are substantially normal. We can therefore consider favourable perspectives for well adjusted and normal relationships among the family members, as well as for the psycho-intellectual development of these children. Furthermore the re-evaluation of the ethical questions and doubts concerning this ‘special experience’ suggests that the sons' and parents' rights have been fully respected.