Aggressive Combination Chemotherapy Research Articles

6 The management of leukaemia in the elderly

Leukaemia is relatively common in the elderly compared to the general population, with over half of all cases of leukaemia occurring in patients aged 65 and over. Special problems are associated with treating patients in this age group. The leukaemias may be intrinsically different, in part because of the high incidence of preceding myelodysplasia. There is increased likelihood of coincident disease. There is lower tolerance to toxic complications, such as infection and bleeding, associated with a decreased resilience of normal haematopoiesis. There is more difficulty in obtaining intravenous access in elderly patients. These problems render patients ineligible for marrow transplants. Myelodysplastic syndromes occur predominantly in the elderly. There are a number of myelodysplastic syndromes now identified, each with its characteristic natural history. Management decisions are based on accurate diagnosis of the specific syndrome, consideration of prognostic features, a period of observation, and conservative treatment principles. More than half the cases of acute myeloblastic leukaemia also occur in the elderly. Prognostic factors must be examined and the literature carefully scrutinized for results pertinent to the elderly patient. In some patients treatment may be justifiably withheld, others may benefit from low dose cytosine arabinoside and some patients should receive aggressive combination chemotherapy. Management of the chronic leukaemias in the elderly is a less controversial area. Chronic lymphocytic leukaemia is the most common of the leukaemias in this age group. Prognostic factors can be determined using staging criteria. observation alone is indicated in many patients. Chlorambucil and prednisone are the most widely used drugs for symptomatic disease. Aggressive combination chemotherapy may benefit a few patients with advanced or refractory CLL. Hairy cell leukaemia is a rare disorder but many of the patients are over age 65. The elderly male patient may have a particularly benign course and require no therapy. Splenectomy is the standard first line of therapy, but recombinant alpha-interferon is sufficiently effective and non-toxic that it should be the treatment of choice in some patients. Deoxycoformycin is also effective in preliminary trials and may soon be routinely indicated. It is not often appreciated that half of all patients with chronic myelogenous leukaemia are aged 65 and over.(ABSTRACT TRUNCATED AT 400 WORDS)

Is cranial radiation necessary for cns prophylaxis in pediatric NHL?

The records of 95 consecutive children ≤21 years of age with previously untreated diffuse histology NHL registered in our protocols from 1978 to 1983 were reviewed. Seventy-nine patients were considered eligible for analysis. The histologic subtypes represented included lymphoblastic (LB) 37%; histiocytic (DHL) 29%; undifferentiated (DU) 19%; poorly differentiated (DPDL) 9%; and unclassified (UNHL) 6%. Distribution of the patients according to stage showed Stage 1, 0%; Stage 11, 11%; Stage 111, 53%; Stage IV, 36%. Four different Memorial Hospital protocols for systemic chemotherapy were used (LSA2L2 73%; L10 9%; L1710%; L17M 8%); however, the IT (intrathecal) chemotherapy was uniform (Methotrexate: 6.0–6.25 mg/M 2 per treatment course) and was included in the induction, consolidation, and maintenance phases of all treatment protocols. Cranial radiation was not included in the CNS prophylaxis program. The overall median time of follow-up was 43 months. The overall CNS relapse rate was 6.3%, however, the incidence of CNS lymphoma presenting as the first isolated site of relapse in patients in otherwise complete remission (minimum follow-up of 19 months with 97% of patients off treatment) was only 1 58 (1.7%). Our data suggests that IT chemotherapy when given in combination with modern aggressive systemic combination chemotherapy, and without cranial radiation appears to be a highly effective modality for CNS prophylaxis regardless of stage, histology, or bone marrow or mediastinal involvement. Therefore, with the commonly used aggressive combination chemotherapy for the management of all stage diffuse pediatric NHL, and the known increased risk of leukoencephalopathy with combination of cranial radiation and intensive systemic and intrathecal chemotherapy, we believe that cranial radiation may not be indicated for CNS prophylaxis in pediatric NHL.

Malignant Lymphoma of the Testis

Malignant lymphomas of the testis account for approximately 5 percent of testicular neoplasms, and they are the most common testicular malignancy between the ages of 60 and 80. Testicular lymphoma has a propensity to be associated with involvement of the skin, the central nervous system, Waldeyer's ring and adjacent structures, and the contralateral testicle. In general, essentially all patients with testicular lymphoma have been categorized as having poor-risk non-Hodgkin's lymphoma, with diffuse histiocytic lymphoma being the most common histologic subtype. All patients with testicular lymphoma should be treated with aggressive combination chemotherapy, with or without radiotherapy.

The non-hodgkin's lymphomas: pathology, staging, treatment

The non-Hodgkin's lymphomas include a broad range of neoplasms derived from the T cells and B cells and their precursors in the lymphoid system. Although they are not among the most common cancers, the lymphomas have engendered a great deal of interest among researchers because of their interesting biology and responsiveness to therapy. The non-Hodgkin's lymphomas include at least ten major subtypes of diseases with different morphologic characteristics and clinical behavior. Based upon survival characteristics, it is convenient to divide the lymphomas into three broad categories, low grade, intermediate grade, and high grade. The low grade lymphomas usually arise in middle age or older individuals (median age, 55 years). They are derived from B cells and often have a folicular architectural pattern. They usually present with advanced stages of disease, often by virtue of bone marrow involvement. Nevertheless, patients are usually asymptomatic and may even have spontaneous regressions of disease. These lymphomas are responsive to a broad range of therapies including irradiation, single agent or multiagent chemotherapy, or combined modality therapy. They also are affected by treatment with biologicals such as alpha interferon and monoclonal antibodies. Unfortunately, response to any of these therapies is often transient and relapse is common. The intermediate grade lymphomas include the common large cell lymphomas (follicular or diffuse) and diffuse mixed cell lymphoma. These lymphomas, together with the high grade immunoblastic lymphoma, are often grouped together for the development of management strategies. These lymphomas may be derived from B cells or T cells. They occur over a broader age range than the low grade lymphomas and they are much more aggressive in their natural behavior. Effective treatment programs have been developed for both limited and advanced clinical stages of disease. In limited disease, moderately intensive chemotherapy is often combined with involved field irradiation. In advanced stage disease, more aggressive combination chemotherapy programs are usually employed. From 40% to 80% of patients may be cured with these approaches, depending upon the initial extent of disease. Two types of high grade lymphoma-lymphoblastic and small noncleaved cell are particularly aggressive in their behavior. Lymphoblastic lymphoma is a T cell lymphoma that often arises in adolescent males and presents with a large mediastinal mass, marrow, and CNS involvement. It closely resembles acute lymphoblastic leukemia (ALL) and similarly intensive chemotherapy programs as are utilized in ALL may be successful in its management. Small noncleaved cell lymphoma is a B cell lymphoma that commonly presents with bulky disease, often involving intra-abdorninal sites such as the mesentery and gastrointestinal tract. This lymphoma has a short cell cycle time and rapid tumor doubling time and prompt initiation of treatment is indicated, in view of the poor prognosis for patients who present with either of these high grade lymphomas in the presence of adverse prognostic factors such as an elevated lactic dehydrogenase (LDH) or bone marrow involvement, investigational programs such as intensive systemic therapy combined with whole body irradiation, and bone marrow transplantation are being explored.

The second-look operation in advanced ovarian cancer--experiences since the introduction of cisplatin combination chemotherapy

In cases of ovarian carcinoma the trend today is toward postoperative cytostatic follow-up therapy which is as aggressive as possible, though of limited duration. The aim is to achieve full clinical remission and to verify it histologically by a second-look-operation. This paper presents the results obtained in 41 women who underwent second-look surgery, out of a total of 87 women with advanced epithelial ovarian carcinoma (FIGO stage III and IV) who had been given combination chemotherapy with cisplatin postoperatively. Taking various well-known prognostic factors into account (stage, age, histologic grading, primary postoperative residual tumor mass), the situation before and after a second-look laparotomy was analyzed. The survival data (life table analyses according to Kaplan-Meier) indicate the importance of these prognostic factors. Approximately one-third of the patients had full clinical remission after aggressive cisplatin combination chemotherapy; complete remission was verified microscopically in 18% of all cases, with a mean of 12 biopsies. The long-term prognosis for such women, who can be cured even if they have primary advanced ovarian carcinoma, is likely to be good. In addition, present-day indications and the standard surgical procedure for a second-look operation are described.

Small cell lung cancer.

Lung cancer is the predominant fatal neoplasm of our time, and SCLC, which accounts for about 25% of all lung cancer, if untreated results in death in about 3 months. Currently employed aggressive combination chemotherapy has allowed a 4- to 5-fold improvement in median survival over untreated patients. Ten to 20% of patients with limited disease can be expected to have a long-term (2-yr) survival. The majority of patients, however, have extensive disease. For these patients the median survival is about 7 months. Less than 2% survive 2 yr. During the last 10 yr, experience in the treatment of thousands of patients has been reported. These trials, using a large variety of drug combinations, doses, and schedules as well as multiple modalities including radiotherapy, surgery, and bone marrow transplantation, demonstrate that a plateau has been reached with our present therapeutic approach. The development of new effective therapeutic strategies as well as prevention of SCLC require a better basic understanding of the cellular pathophysiology of the disease. A consistent chromosomal abnormality has been associated with SCLC. This may provide new insight into predisposition and pathogenesis of SCLC. How this chromosomal abnormality relates to loss of control of cell growth is under intense investigation. Similarly, during the past 3 yr, the identification of growth regulatory oncogenes has greatly improved our understanding of malignancy. The discovery that metastatic cells escape immune surveillance has led to attempts at modulating antigenic expression. The modulation of cellular antigenic expression may facilitate the destruction of tumor cells by host defense mechanisms. The understanding of the genetic basis of drug resistance may lead to approaches that prevent or delay resistance. This century has witnessed the emergence of SCLC as an important fatal neoplasm. It has also been during this time that another, formerly dominant pulmonary condition, tuberculosis, has been controlled. The reduction of tuberculosis was accomplished by a combination of scientific understanding, beginning with the discovery of Koch's bacillus, and public health measures. Perhaps a similar parallel for SCLC as well as other forms of cancer will be written. Basic cellular investigations with the new tools of molecular biology as well as measures to control exposure to predisposing environmental factors such as component of cigarette smoke may one day lead to control of SCLC.

MALIGNANT HISTIOCYTOSIS IN CHILDHOOD

Clinicopathological features of four paediatric cases of malignant histiocytosis (MH) are described. The patients all presented with fever, lymphadenopathy and anaemia. Two died from widespread disease within one month. Two patients, who received combination chemotherapy, were brought into remission and are currently without disease after 30 and 60 months, respectively. Diagnosis was made on the basis of infiltration by a mixture of anaplastic and well-differentiated phagocytic histiocytes in skin, lymph node, bone marrow and spleen. Immunohistochemical studies showed variable presence of lysozyme, alpha 1-antitrypsin (AT), and alpha 1-antichymotrypsin (ACT). Concanavalin A (Con A) receptors, recently suggested as a histiocyte marker, were found in the proliferating cells in all cases. S-100 protein was absent. The findings suggest that the prognosis in childhood MH remains guarded but not hopeless with aggressive combination chemotherapy. The presence of Con A receptors in paediatric MH cells with a more constant occurrence than lysozome, AT and ACT seems promising as an additional diagnostic tool although further studies are needed to examine the specificity of Con A receptors in relation to various other disorders of histiocytic proliferation.

Prognostic factors in non-Hodgkin's lymphoma

The results obtained with the various types of treatment in non-Hodgkin's lymphoma are reviewed and the data from the recent EORTC trials are summarized. In patients with Stage I follicular histology, regional radiotherapy (RT) alone gives excellent results. The long-term relapse-free survival (RFS) is high and relapsing patients can be rescued by aggressive combination chemotherapy; initial chemotherapy with CVP improves RFS but not total survival (TS). In patients with Stage I diffuse histology, the long-term survival is less satisfactory. CVP chemotherapy does not improve either RFS or TS; therefore if adjuvant chemotherapy is justified, it should be more aggressive than CVP. In patients with Stage II follicular type, regional radiotherapy alone gives good results. The addition of abdominal bath irradiation to regional RT increases RFS but not TS. After relapse, patients can be rescued by combination chemotherapy. In patients with Stage II diffuse histology, extended RT followed by CVP gives poor results and RT should be combined with more aggressive combination CT; the preliminary results of an integrated alternating regimen being excellent. In patients with Stage III and IV follicular type, the 8 year TS of patients treated with combination Cr regimen (CHVP) followed by localized irradiation is approximately 55%, however the indications for the various types of treatment are still unclear. In patients with diffuse Stage III and IV, the results obtained with a combination CT regimen (CHVP) are still unsatisfactory, but are better in patients treated by a more aggressive CT regimen (CHVP-Bleo-VCR). Therefore aggressive CT associated with localized irradiation appears to be the best treatment. Further research should aim to identify the optimal combination CT regimen. In patients with high grade lymphomas who have relapsed the use of bone marrow autografts will be investigated. The present data show that besides histological type and age, the main prognostic factor is total tumor body burden as assessed by clinical stage, number of involved lymph node areas, and bulk of the disease. The study of the biological characteristics of the disease may provide more powerful prognostic indicators.

Improved survival in the treatment of advanced Hodgkin's disease at a nonuniversity institution (1970-1979).

From 1970 through 1979, 89 patients with Hodgkin's disease were treated at the Marshfield Clinic/St. Joseph's Hospital. After the pathologic material was reviewed, the patients were analyzed to compare Group I (1970-1973) with Group II (1974-1979). Demographic characteristics in the two groups were similar. In the decade, 76% of patients achieved complete remission. In advanced-stage disease, 50% of patients achieved complete remission in Group I compared with 68% in Group II. At 5 years, 50% of patients were alive without COPP (cyclophosphamide, vincristine, procarbazine, prednisone) chemotherapy; with this treatment, 75% of patients survived (P = 0.02). There was improved survival comparing Group I (56% at 5 years) with Group II (76% at 5 years) patients with advanced disease (P = 0.004). More aggressive combination chemotherapy (COPP) was related to the improvement in survival (P less than 0.001). The advances in treatment made by cooperative groups and universities are being transferred to nonuniversity institutions, with appropriate improvement in survival of Hodgkin's disease.

Primary extranodal non-hodgkin's lymphoma

A total of 52 of 238 patients (22%) with non-Hodgkin's lymphoma presented with disease in a primary extranodal site. The gastrointestinal tract was the commonest site involved (50%) and diffuse large cell was the commonest histological sub-type of the lymphoma (64%). Survivorship analysis of these patients, treated predominantly with chemotherapy, suggests that long-term survival is associated with: low-grade malignancy--median survival greater than 120 months; localized disease or spread of disease confined to the regional lymph nodes--median survival 65.5 months; and the use of aggressive combination chemotherapy for intermediate grade malignancy when the disease is localized or spread is confined to the regional lymph nodes--median survival greater than 110 months.

Aggressive combination chemotherapy in multiple myeloma. A multicentre trial

A one‐armed multicentre trial was conducted in Finland during the period from Jan. 1979 to Feb. 1980 to document the possible beneficial effect of aggressive combination chemotherapy MOCCA on the remission induction and survival in multiple myeloma. The regimen MOCCA consisted of vincristine, methylprednisolone and 3 alkylating agents. Of the 50 patients eligible for the for study, 39 (78%) achieved at least a 50% response. 27 (54%) achieved an excellent response. The median survival time for all patients was 49 months from the initiation of the treatment, but 23 of the 33 patients whose myeloma protein had shown a ≥ or ≧ 75% reduction were still alive at 4 yr. Advanced clinical stage and irreversible renal damage had a negative prognostic value. After 12 months on regimen MOCCA the patients with a ≧ or ≥ 75% reduction in myeloma protein were allocated at random to receive MOCCA courses bimonthly or no further chemotherapy. The maintenance chemotherapy did not prolong remission or survival.

Mediastinal germ cell tumors in childhood: A clinical and pathological study of 21 cases

Twenty-one patients aged 16 years or less had been treated for a primary mediastinal germ cell tumor at the Children's Hospital, Boston Massachusetts, during the last 54 years. There were 13 boys and eight girls with the average age at diagnosis being 7 years (range 2 weeks to 16 years). Twelve mediastinal germ cell tumors were classified as pure teratoma, five contained embryonal carcinoma admixed with other germ cell components, and four were pure embryonal carcinoma. Of 12 patients with pure teratoma, 10 underwent complete surgical resection and were alive and well 1 to 13 years later; two children left untreated died of complications related to local tumor growth. Complete surgical resection was possible for only two of nine patients with embryonal carcinoma; both received adjuvant therapy and were alive and well 3 and 20 years later. Seven patients received radiation and/or chemotherapy but died of residual or metastatic disease. Successful treatment for children with embryonal carcinoma requires an operation aimed at either debulking or complete resection (if possible) coupled with early and aggressive combination chemotherapy. The role of radiation in primary therapy remains undefined with regard to curative intent.

Malignant germ cell tumors of the mediastinum

A review of 56 cases of primary malignant germ cell tumors of the mediastinum revealed that, as with benign teratomas, the tumors occurred in young adults (mean age 29 years) but that the sex distribution differed (86% male and 14% female). A single germ cell element was found in 37 (66%) of the tumors, and various combinations were present in the remaining 19 (34%). The tumors were classified among five recognized types of germ cell tissues. There were 24 seminomas (22 pure and two with mature teratomas), 17 embryonal carcinomas (nine pure and eight with mixtures), five teratomas, seven choriocarcinomas (three pure and four with mixtures), and three pure yolk sac tumors. Most (86%) of the patients were symptomatic at the initial examination, with chest pain, cough, and loss of weight being the most frequent presenting symptoms. The standard posteroanterior and lateral roentgenograms were the most helpful diagnostic tool, showing evidence of an anterior mediastinal mass in 53 patients. The diagnosis was established by surgical exploration of the mediastinum or by biopsy of a lymph node in 55 patients. Of the 55, 24 (43.6%) had complete resection of the tumor and 31 (56.4%) had incomplete resection or biopsy alone. The overall prognosis for mediastinal germ cell tumors is poor, partly because the tumors are far advanced at the time of diagnosis but also because some of the tumors that contain embryonal cell carcinoma, choriocarcinoma, and yolk sac elements are very aggressive. Factors that were prognostic in patients with seminoma--such as age, presence of the superior vena caval syndrome, lymphadenopathy, evidence of hilar disease on the chest roentgenogram, and resectability--were not predictive in patients with other types of malignant germ cell tumors. Although aggressive combination chemotherapy may represent a significant treatment modality for nonseminomatous mediastinal tumors, the present study spanned many years in which no chemotherapy was available. Patients in the later years of the study received combination chemotherapy with various treatment regimens. No conclusions concerning specific chemotherapy, therefore, can be derived from this study.

Malignancies in the AIDS patient: natural history, treatment strategies, and preliminary results.

Almost 40% of the 3000 US patients with acquired immunodeficiency syndrome (AIDS) have a malignancy at the time of reporting, and the incidence of AIDS patients who develop a malignancy during the course of the disease may be 65-70%. 2 types of malignancies have been noted with increased frequency in AIDS victims: Kaposi's sarcoma and malignant lymphomas. About 35% of all AIDS patients and 50% of homosexual or bisexual victims have developed Kaposi's sarcoma, and those with coincident opportunistic infection have 2.5 times the mortality of those without such infection. There are 2 essential features to the histopathology of Kaposi's sarcoma: 1) vascular proliferation and 2) spindle-shaped neoplastic cells in a network of reticulin fibers that appear to be of endothelial origin. The treatment of the epidemic form of Kaposi's sarcoma has not been successful, and the projected 2-year survival is only 30%. The causes of death in the majority of such patients are overwhelming opportunistic infections, especially cytomegalovirus and Pneumocystis carinii, and irreversible cachexia and wasting. Interferon therapy has had a beneficial effect in patients with disease limited to skin, with T4/T8 ratios over 0.5, and without a prior history of opportunistic infection; however, there is no evidence that interferon exerts any beneficial effects on the underlying immune defects. An aggressive 6-drug combination chemotherapy regimen has been tried on patients whose tumors appeared to be life-threatening and was effective in controlling the Kaposi's sarcoma, but again did not appreciably alter immune parameters. Several other approaches to the treatment of epidemic Kaposi's sarcoma are under evaluation, including gamma interferon, interleukin-2, and plasmapheresis. Patients who develop malignant lymphomas require combined treatment with central nervous system radiation and systemic combination chemotherapy. There is no evidence that the antitumor responses obtained in AIDS-related malignancies translate into survival advantages to the AIDS victim.

Pilot studies of superfractionated radiotherapy and combination chemotherapy in limited oat cell carcinoma of the bronchus

There are sound radiobiologic and suggestive clinical rationale for superfractionating the radiotherapeutic regimens employed for the therapy of rapidly growing malignancies. Oat cell carcinoma of the bronchus is such a tumor. We report our experience combining aggressive systemic combination chemotherapy with superfractionated radiotherapy for the treatment of “limited” oat cell carcinoma of the bronchus. Overall, patient tolerance was satisfactory and a complete remission rate of 74% was achieved. It remains to be proven, in a prospective randomized fashion, whether this approach is superior to current conventional management.

Incidence of hypothyroidism following multimodality treatment for advanced squamous cell cancer of the head and neck.

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.

In Vitro radiation studies on Ewing's Sarcoma cell lines and human bone marrow: Application to the clinical use of total body irradiation (TBI)

Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and focal irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, we have studied the in vitro radiation response of two established cell lines of Ewing's sarcoma and human bone marrow CFUc. The Ewing's fines showed a larger D 0 (1.26 Gy, 2.04 Gy) and n (6.0, 3.2) compared to the bone marrow CFUc (D 0 = 0.86 Gy, n = 1.2). No repair of potentially lethal radiation damage (PLDR) was found after 4.5 Gy in plateau phase Ewing's sarcoma cells. A theoretical split dose survival curve for both the Ewing's sarcoma fines and human bone marrow CFUc using this TBI schedule shows a significantly lower surviving fraction (10 −4–10 −5) for the bone marrow CFUc. Based on these in vitro results, two 4.0 Gy fractions separated by 24 hours is proposed as the TBI regimen. Because of the potentially irreversible damage to bone marrow, autologous bone marrow transplantation following the TBI is felt to be necessary. The details of this clinical protocol in high risk Ewing's sarcoma patients are outlined.

The diagnosis and treatment of yolk sac tumors in infants and children

Tumors of germ cell origin are the most frequently diagnosed malignant neoplasms of the ovary and testis in infants and children. Although the more frequent adult histological subtypes, such as embryonal carcinoma and seminoma (dysgerminoma), do occur in the pediatric population, one subtype occurs almost exclusively in children. This is the endodermal sinus or yolk sac tumor (YST), so named by Teilum in 1959 because of the resemblance of this tumor to the endodermal sinuses of the rat placenta described by Duval (210). This tumor has been recognized at several extra-gonadal sites, including the presacral area, the anterior mediastinum and the pineal; and, with the exception of tumors originating in the testis, is associated with a poor prognosis. We will review the diagnosis and management of the YST, and will suggest areas where the use of aggressive combination chemotherapy may lead to improved survival of infants and children with this tumor.

Restoration of normal hematopoiesis by bone marrow ablation and allogeneic marrow transplantation in a case of Hodgkin's disease therapy-related preleukemia

Therapy-related leukemias are generally preceded by a preleukemic phase of several months duration, characterized by pancytopenia, abnormal bone marrow findings, and nonrandom chromosomal abnormalities in almost all cases. No specific therapeutic guidelines are recommended in this preleukemic phase or any other type of preleukemia; aggressive combination chemotherapy is usually withheld until the full expression of leukemia. A 22-yr-old man with therapy-related preleukemia following treatment of Hodgkin's disease received as primary treatment ablative chemotherapy followed by marrow transplantation from his histocompatible sister. At day 316, the patient is still in complete bone marrow recovery with a normal donor karyotype. In the light of the very poor results obtained with conventional chemotherapy regimens once the leukemic phase is established, we suggest that bone marrow transplantation, if undertaken before leukemic conversion, may be the treatment of choice in young adults with therapy-related preleukemia.

Restoration of Normal Hematopoiesis by Bone Marrow Ablation and Allogeneic Marrow Transplantation in a Case of Hodgkin's Disease Therapy-Related Preleukemia

Therapy-related leukemias are generally preceded by a preleukemic phase of several months duration, characterized by pancytopenia, abnormal bone marrow findings, and nonrandom chromosomal abnormalities in almost all cases. No specific therapeutic guidelines are recommended in this preleukemic phase or any other type of preleukemia; aggressive combination chemotherapy is usually withheld until the full expression of leukemia. A 22-yr-old man with therapy-related preleukemia following treatment of Hodgkin's disease received as primary treatment ablative chemotherapy followed by marrow transplantation from his histocompatible sister. At day 316, the patient is still in complete bone marrow recovery with a normal donor karyotype. In the light of the very poor results obtained with conventional chemotherapy regimens once the leukemic phase is established, we suggest that bone marrow transplantation, if undertaken before leukemic conversion, may be the treatment of choice in young adults with therapy-related preleukemia.