Role of bone marrow examination in staging Hodgkin's disease: experience in México

We assessed the value of bone marrow biopsy prospectively in a group of 91 individuals with Hodgkin's disease. The median age of our population was 29 years (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing disease and most patients (44%) were in pathological stage II at diagnosis. The bone marrow biopsy showed infiltration by Hodgkin's disease in only three individuals (3.3%); two of these patients displayed constitutional symptoms and had been assigned to stage III before the biopsy. In one case, bone marrow biopsy was the diagnostic procedure, which was performed as part of the investigation of fever of unknown origin. Follow-up periods ranged between 1 and 117 months (median 16 months). All patients achieved complete remission, seven patients relapsed and four were given autologous stem cell transplants. The median survival of the whole group was 117 months, while the 3500-day survival was 76%. As bone marrow biopsy was the diagnostic procedure in one case, bone marrow biopsy was a useful staging procedure in only 2.2% of patients (two out of 90 patients). We suggest that bone marrow biopsy should be only be performed as a staging procedure in a selected subset of patients with Hodgkin's disease (clinical stage III, B symptoms, etc.).     

Hodgkin's disease in patients over sixty years old

Fifty-two patients 60 to 75 years of age were treated for Hodgkin's disease at Stanford University between 1968 and 1980. Adequate staging was defined as including a lymphogram and staging laparotomy for stage I to III and a positive bone marrow or liver biopsy or other evidence of diffuse involvement of extralymphatic tissues for stage IV. Adequate treatment was defined as subtotal lymphoid irradiation for pathologic stages I to IIA; total lymphoid irradiation for stages IIB to IIIA; and chemotherapy with or without irradiation for stages IIIB to IV. Twenty-four patients (46%) had advanced disease (IIIB to IV). Those patients who received appropriate treatment had a median survival of only 39 months. Of the 28 patients with limited disease (I to IIIA), 15 had laparotomy and adequate treatment. Thirteen did not have a laparotomy and 7 were treated with involved-field irradiation. The 5-year survival rate in the laparotomy-staged and adequately treated group was 86%, but in the clinically staged group, only 35% (p = 0.006).     

Is Staging Laparotomy of Therapeutic Value in Patients with Supradiaphragmatic Hodgkin's Disease,Clinical Stage IA-IIA?

Between 1968 and 1972, 123 patients with clinical stage (CS) IA and IIA Hodgkin's disease were seen. Staging laparotomy was introduced in June 1970. The impact of staging laparotomy on the prognosis has been evaluated by comparing the treatment results before and after the introduction of this procedure. The patients were treated only on the basis of CS before staging laparotomy, and mainly on the basis of pathological stage (PS) after the introduction of this procedure. Patients with stage IA to IIIA disease received radiotherapy alone with the extended field techniques, while patients with stage IVA disease had combination chemotherapy. After an observation time of 7 years there was no difference in survival between the two groups. The relapses occurred earlier in the patients treated after the introduction of staging laparotomy. It is shown that the survival is unaffected by staging laparotomy in the patients with Hodgkin's disease CS IA and IIA.     

CHEMOTHERAPY OF CHILDHOOD HODGKIN'S DISEASE IN UGANDA

In a 5-year period, 24 Ugandan children Summary with Hodgkin's disease were systematically evaluated, staged, and treated uniformly with combination chemotherapy (nitrogen mustard, vincristine, prednisone, procarbazine). All patients (7 stage I-II, 12 stage III, and 5 stage IV) had complete remissions. 5 of 21 adequately treated patients relapsed, with a median remission duration of 12 months, and all responded completly when combination chemotherapy was 89%; 2 patients died, both of causes not attributable to active Hodgkin's disease. The initial remission was sustained in all 7 patients with localised Hodgkin's disease.     

Trephine needle bone marrow biopsy in the initial staging of Hodgkin disease: sensitivity and specificity of the Ann Arbor staging procedure criteria

The purpose of this study was to test the value of the Ann Arbor staging procedures committee criteria in defining a group of newly diagnosed patients with Hodgkin disease who do not have involvement of the bone marrow and do not need this procedure performed. One hundred sixty-six bilateral and 16 unilateral trephine bone marrow biopsies were performed in a consecutive series of 182 patients undergoing initial staging for Hodgkin disease. Bone marrow involvement was found in 13 patients. Advanced stage, defined as stage III or IV, occurring in 92%, anemia occurring in 100%, and "B" symptoms present in 100% were found to be the most sensitive indicators for bone marrow involvement. Osseous disease (99%), platelet count less than 150,000/mm3 (98%), and WBC less than 4,800/mm3 (94%) were the most specific parameters. The known association of bone marrow involvement with older patients, lymphocyte depleted histology, lower blood cell counts, anemia, advanced stage, and poorer survival is verified. The Ann Arbor staging procedures committee criteria for performing a bone marrow biopsy were shown to be 100% sensitive and 40% specific. Use of these criteria would have found all 13 patients with bone marrow involvement. Of the 73 patients who did not meet the criteria, no patient had bone marrow involvement. Use of the Ann Arbor staging procedures committee criteria is recommended.     

The significance of the bone marrow biopsy pattern in chronic lymphocytic leukemia: a prognostic dilemma

Although bone marrow biopsy pattern (BMBP) has long been suggested to be an independent prognostic factor in chronic lymphocytic leukemia (CLL), conflicting reports continue to appear in the literature. To investigate this issue we retrospectively reviewed 70 CLL patients who had undergone bone marrow biopsy at the time of diagnosis in a multivariate Cox regression analysis together with other prognostic factors. There were 51 (72.8%) males and 19 (27.2%) females with a median age of 60 years (range, 38-77). The median follow-up time was 24 months (range, 1-76), and median survival was 44 months. Thirtyfour patients (48.6%) had diffuse and 36 patients (51.4%) had nondiffuse BMBP (14 nodular, 11 interstitial, and 11 mixed). The median survival for diffuse and nondiffuse BMBP groups were 17 and 53 months, respectively (P= 0.05). Sixteen patients (22. 9%) had stage A, 28 (40.0%) stage B, and 26 (37.1%) stage C disease according to the Binet system, and four patients (5.7%) had low-risk, 39 (55.7%) intermediate-risk, and 27 (38.6%) high-risk disease according to the modified Rai staging system. The difference between the median survivals of patients in different stages was statistically significant (P < 0.0001). The BMBP and staging systems that are thought to be significant predictors of prognosis were used to build a multivariate Cox proportional hazard model. BMBP was not found to add additional information to the prognostic value of the staging systems. Our results underline two points: first, the significance of BMBP must be investigated in multivariate analysis including the stage, and second, BMBP is not a dynamic prognostic parameter, it is an index of tumor burden and does not add any prognostic information beyond that provided by clinical stage.     

Value of small percutaneous bone biopsy in staging lymphoma; experience in a regional hospital

Summary. A single small percutaneous bone biopsy was obtained in 107 untreated patients with lymphoma as part of staging. Six out of 52 cases of Hodgkin's disease had positive bone biopsies and three of these relapsed. In 55 patients with non-Hodgkin lymphoma, nine out of 16 with nodular lymphocytic disease and only 12 of 39 with diffuse disease, had positive biopsies. The incidence of relapse and deaths over the time studied was not clearly related to the biopsy results. The results are similar to findings in other series where a larger bone sample was obtained. The value of a single small bone biopsy in lymphoma seems established.     

Sequential laparoscopy and laparotomy combined with bone marrow biopsy in staging Hodgkin's disease.

In a series of 121 unselected, previously untreated patients with Hodgkin's disease staging laparoscopy combined with needle bone marrow biopsy detected the presence of extranodal disease in the liver or marrow or both in 9% of the patients. A spleen biopsy yielded positive findings in 13%. Subsequent laparotomy with open marrow biopsy performed in 110 patients with negative liver and marrow findings from the first combined procedure revealed the presence of extranodal hepatic lymphoma in two additional spleens. Surgical marrow biopsy was always interpretey. Although devoid of major complications, biopsy of the spleen is not recommended as a routine procedure in staging laparoscopy. This prospective sequential study confirms that laparoscopy plus needle marrow biopsy is a useful, rapid, safe, and economic procedure to establish stage IV disease in the large majority of patients with nodal involvement. Considering the recent more extensive use of chemotherapy for intermediate stages of Hodgkin's disease, our findings suggest that laparotomy with splenectomy needs a critical re-evaluation as a routine staging procedure for patients with no overt extranodal lymphoma.     

Prognostic implications of stage of disease and sites of metastases in patients with small cell carcinoma of the lung treated with intensive combination chemotherapy

The influence of various sites of distant metastases on response and survival was analyzed in 106 consecutive previously untreated patients with small cell carcinoma whose disease was systematically staged. All patients received 6 wk of intensive induction chemotherapy with cyclophosphamide, methotrexate, and lomustine; therapy thereafter varied without differential effects on survival. Staging procedures included physical examination, chest roentgenogram, fiberoptic bronchoscopy, bone marrow and liver biopsies, and radionuclide bone, brain, and liver scans. On the basis of pretreatment staging, 33 patients (31%) had limited disease. In the remaining 73 patients, sites of extensive disease included bone in 40; with bone as the sole site of metastatic disease in 13; liver in 30, with liver as the only site in 5; soft tissues in 25 (only site in 7); bone marrow in 22 (only 2); central nervous system in 9 (only site in 4); opposite lung in 7 (only site in 4). Although patients with limited disease live longer than those with extensive disease (median length of survival, 12 versus 10 months), this difference was not significant. This lack of major impact of traditional stage on survival was explained by the similar survival of patients with limited disease and a single site of extensive disease. Prognosis worsened with increasing number of sites of extensive disease (median survival, 11.5, 10, and 8 months for one, two, and three or more sites, respectively). Metastases to the liver or central nervous system significantly shortened survival, whereas involvement of bone, soft tissues, or bone marrow had little adverse effect. In patients with small cell carcinoma whose disease is thoroughly staged and who are given aggressive chemotherapy, certain sites or a small number of sites of extensive disease may be treated as successfully as limited disease.     

Assessment of marrow trephine in relation to staging in chronic lymphocytic leukaemia

The prognostic value of the Rai clinical staging system and of a series of bone marrow features was examined in 167 untreated patients with CLL. The patients fell into three prognostic groups: those with limited disease, Rai stages 0 and I, median survival 107 months; those with intermediate disease, Rai stage II, median survival 44 months; and those with extensive disease, Rai stages III and IV, median survival 27 months. Two types of infiltration patterns, diffuse and nodular, were found in the bone marrow, and these were associated with significantly different median survival times: 34 and 115 months respectively.
It is suggested that diffuse and nodular patterns in the bone marrow relate to the rapidity of progress of the disease rather than to different stages in CLL.
The data suggest that a simplified clinical staging system together with an histological classification reflects both the extent as well as the rate of progression of CLL. The course of CLL may be monitored by sequential bone marrow biopsies to assess changes in the proliferation pattern, in the proliferative cell system and in the tumour mass, which give early warning of shifts in the rate of progression and therefore in the prognosis of the disease.     

Is bone marrow examination in small-cell lung cancer really necessary?

Of 403 patients with small-cell lung cancer, we identified by aspiration, biopsy, or both 67 with bone marrow involvement and found the two procedures to be complementary in detecting marrow involvement. The mean surface area of the positive biopsy specimens was significantly greater than that of a randomly selected group of negative biopsy specimens, suggesting that the larger the specimen, the greater the chance of detecting tumour. Patients with marrow involvement had only a slightly worse prognosis compared with other patients who had extensive disease. Only 7 of the 403 patients (1.7%) had extensive disease based on marrow involvement alone. Because bone marrow examination rarely changes the stage of cancer in noninvasively assessed patients, and has no impact on the tolerance of chemotherapy and only a small effect on length of survival, we do not recommend this procedure in the routine staging of small-cell lung cancer.     

Post-splenectomy lymphocytosis

Summary We describe post-splenectomy lymphocytosis (PSL) in 23 patients, a majority (20/23) of whom have undergone splenectomy as a staging procedure for Hodgkin's disease. The absolute lymphocyte count ranged from 4.0 to 8.7 × 10⁹/l. The lymphocytosis was noted 4–242 (median 70) months after splenectomy and persisted almost unchanged in most patients on prolonged follow up (median 50 months). Immunophenotyping of the lymphocytes revealed no monoclonal B cell population.     

Clinical staging of chronic lymphocytic leukemia.

A method of clinical staging of chronic lymphocytic leukemia (CLL) has been proposed which is based on the concept that CLL is a disease of progressive accumulation of nonfunctioning lymphocytes: stage O, bone marrow and blood lymphocytosis only; stage 1, lymphocytosis with enlarged nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. Analysis of 125 patients. in the present series showed the following median survival times (in months) from diagnosis: stage 0, is greater than 150; stage I 101; stage II, 71; stage III, 19; stage IV, 19, The median survival for the entire series was 71 mo. The prognostic significance of the stage remained even after adjustment was made for age and sex. However, both sex and age were shown to be poor predictors of survival after adjustment for stage. The method of staging proved to be a reliable predictor of survival whether used at diagnosis or during the course of the disease. The proposed staging system was an equally accurate indicator for survival when applied to two other previously published studies of large series of patients     

Incidence of ‘Dry Tap’ on Bone Marrow Aspirations in Lymphomas and Carcinomas

Of 2 907 bone marrow aspirations in patients with various malignancies, 192 or 6.6 % exhibited ‘dry tap’. In about 80 % of the ‘dry tap’ there was material present inside the bone marrow needle which gave smears useful for evaluation of the bone marrow cytology. About 23 % displayed normal cytology. Bone marrow involvement could be diagnosed in 13 out of 55 ‘dry tap’ in Hodgkin's disease, 41 out of 46 in chronic lymphocytic leukaemia and lymphosarcoma, 6 out of 20 in reticulum cell sarcoma, 6 out of 9 in myelomatosis and 20 out of 45 in carcinoma. In a material of 174 aspirations with tumour cells in the bone marrow aspirate, the highest incidence of ‘dry tap’ was found in patients with Hodgkin's disease and patients with carcinoma, the lowest incidence in patients with multiple myeloma.     

Bone marrow and peripheral blood involvement in mantle cell lymphoma

The peripheral blood smears, bone marrow aspirates and biopsies of 46 patients with mantle cell lymphoma were reviewed. The diagnosis of mantle cell lymphoma was established in all cases on extramedullary tissue samples using standard morphologic, phenotypic and molecular genetic criteria. 27/35 patients (77%) had circulating lymphoma cells (median 20% of all circulating white blood cells; range 5–90%) identified by morphology at some point during the course of their disease. No statistical difference in survival was detected in patients with or without peripheral blood involvement. Lymphoma was identified in bone marrow aspirate specimens from 33/40 patients (83%) and in bone marrow biopsy specimens from 39/43 patients (91%). The pattern of marrow biopsy involvement was nodular (31 cases; 82%), interstitial (19 cases; 50%), paratrabecular (17 cases, 45%) and diffuse (12 cases; 32%). Although the median survival of patients with ≥ 50% bone marrow involvement was 13 months, and the median survival of patients with ≤ 50% was 49 months, no statistically significant differences between these small subgroups were observed. Mantle cell lymphoma frequently involves the peripheral blood and bone marrow. Its appearance is distinctive but variable, and immunophenotypic studies as well as morphologic confirmation by a biopsy of tissue other than bone marrow is still required for diagnosis.     

Comparison of initial lymphoma staging using computed tomography (CT) and magnetic resonance (MR) imaging

While MR is known to be superior to other imaging methods for detecting marrow involvement by lymphoma, MR is also capable of detecting abnormal lymph nodes. Our objective was to determine whether MR employing short Tl inversion recovery (STIR) was comparable to CT in the initial staging of 23 patients with Hodgkin's disease (12 patients) and non-Hodgkin's lymphoma (11 patients). MR images of chest, abdomen, pelvis, and femoral marrow were obtained using the STIR and T1-weighted spin-echo (T1-SE) techniques, employing a protocol initially designed for marrow assessment. In all cases, CT-detected adenopathy was also found by MR. Four patients had marrow involvement by MR, undetected by CT. We conclude that MR and CT may be equivalent imaging modalities in the detection of nodal involvement, and that MR has an advantage in its ability to diagnose marrow involvement. Given the high frequency of focal marrow abnormalities detected by MR in patients with Hodgkin's disease and high-grade non-Hodgkin's lymphoma, MR may be the preferred staging modality for these patients. © 1994 Wiley-Liss, Inc.     

Poor hematopoietic stem cell mobilizers: A single institution study of incidence and risk factors in patients with recurrent or relapsed lymphoma

The purpose of this retrospective study was to determine the incidence and predictive factors if any, of mobilization failure in lymphoma patients referred for autologous stem cell transplantation. A total of 588 lymphoma patients were referred for transplant consultation from January 2003 to December 2004. Predictors of mobilization failure were evaluated using logistic regression analysis including diagnosis, mobilization regimen, age, sex, type and number of prior chemotherapies, bone marrow cellularity, platelet count, white count, prior bone marrow involvement with malignancy, and prior radiation therapy. Two hundred and six patients were eligible for transplantation and underwent stem cell mobilization. Twenty‐nine (14%) patients failed to mobilize adequate stem cells after the first attempt. For the entire group age (≥60 versus <60 years), diagnosis (Hodgkin's versus non‐Hodgkin's lymphoma), use of cytokines alone, platelet count <150 × 10⁹/L, and bone marrow cellularity <30% were significant predictors for mobilization failure on univariate analysis. In view of small number of patients multivariate analysis was not possible. However, a low platelet count (150 × 10⁹/L) was the only significant predictor when the analysis was restricted to non‐Hodgkin's lymphoma patients who were mobilized with chemotherapy. Mobilization failure rates are higher in patients with non‐Hodgkin's lymphoma compared with those with Hodgkin's lymphoma. In the subset of patients who undergo chemomobilization for non‐Hodgkin's lymphoma platelet count at the time of mobilization is a predictor of mobilization failure. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Serum Ferritin and Bone Marrow Haemosiderin in Patients with Malignancies and in Healthy Controls

Serum ferritin has been analysed and bone marrow haemosiderin evaluated in 306 patients with malignancies, mostly lymphomas, and in 46 healthy controls. Also haemoglobin, serum iron, transferrin and liver enzymes were analysed simultaneously. 60% of the patients had serum ferritin above normal values and 20% had values above 1000 μg/1. There was a good correlation between serum ferritin and bone marrow iron both in the patients and in the controls, r = 0.67 and r = 0.77, respectively. There was a negative correlation between serum ferritin and haemoglobin concentration in the patients and a positive correlation in the controls. In patients with Hodgkin's disease serum ferritin was related to the stage of the disease.     

Serum hyaluronan is increased in malignant lymphoma

The serum concentration of hyaluronan (HYA) was measured in 41 patients with malignant lymphoma, including 21 patients with non-Hodgkin's malignant lymphoma and 20 patients with Hodgkin's disease. Thirty-four patients were studied at diagnosis. The remaining 7 patients had relapsing or resistant disease. The patients were categorized into four stages according to conventional staging procedures. The median serum HYA concentration in patients with malignant lymphoma was significantly higher (median 40.7 ng/ml; 95% confidence limits 26.1–57.6 ng/ml) than in an age-matched healthy reference group (median 14.5 ng/ml, 95% confidence limits 11–19.4 ng/ml) (P = 0.00032). The highest serum HYA levels were found in patients with relapsing/resistant disease, all being in stages III and IV (median 181.5; range 11.9–500 ng/ml), as compared to previously untreated patients (median 29.8; range 9.1–108) (P = 0.0002) and controls (median 14.2; range 6.7–51.2). Decreased uptake and degradation of HYA owing to malignant transformation of lymphatic tissue is the most plausible explanation to these findings.     

Autologous bone marrow transplantation for advanced stage adult lymphoblastic lymphoma in first complete remission. A pilot study of the non-Hodgkin's Lymphoma Co-operative Study Group (NHLCSG)

Twenty successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA2-L2-type protocol to induce first complete remission. Twelve patients in first CR (median age 22 years, range 15-43), after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation, underwent autologous bone marrow transplantation. Of these 12 patients at diagnosis, one was in stage III and 11 in stage IV; 11 showed mediastinal and seven showed bone marrow involvement. The transplant procedure was well tolerated and no treatment-induced deaths occurred. At this time nine patients are alive and well 25-44 months post-transplant (median follow-up 36 months) with an actuarial disease-free survival of 75%. These early results suggest that high-dose chemoradiotherapy followed by autologous bone marrow transplantation may improve long-term disease-free survival in advanced stage adult lymphoblastic lymphoma. In order to draw definite conclusions, however, a larger and randomized study is needed.